Dissertations / Theses: 'Intrauterine growth restriction (IUGR)'

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Hrabálková, Lenka. "The importance of poly(A)-binding protein 4 (PABP4) in healthy pregnancy." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/22923.

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Healthy pregnancy requires a tightly regulated materno-fetal dialogue for processes such as embryo implantation, endometrial decidualisation (in the mouse), placentation and maternal adaptation to occur. Disruption of placental development as well as maternal adaptation can lead to fetal intrauterine growth restriction (IUGR) which increases the risk of late miscarriage/stillbirth (e.g. 53% of preterm stillbirth and 26% of term stillbirth are found to be IUGR). Furthermore, IUGR is a risk factor for neurodevelopmental conditions in childhood and for a spectrum of related adult health disorders such as cardiovascular disease and type II diabetes, often termed metabolic syndrome. Despite these pregnancy disorders being common (e.g. 1 in 200 pregnancies results in stillbirth in the UK) the molecular lesion(s) underlying their pathophysiology are poorly understood and in particular those with placental and/or maternal aetiologies most frequently remain unexplained. Here we investigate the hypothesis that poly(A)-binding protein 4 (PABP4) is required for healthy pregnancy in mice. PABP4 is an RNA-binding protein and a member of the PABP family which are central regulators of mRNA translation and stability. Using all four permutations of wild-type and knock-out crosses, we find that maternal PABP4-deficiency results in a reduced litter size and IUGR. The number of implantations at e8.5 were not reduced in Pabp4-/- females, implying that the reduced litter size was not a consequence of decreased ovulation, fertilisation or implantation frequency. Further longitudinal analysis (at e13.5, e15.5 and e18.5) reveals that fetal death primarily occurred between e18.5 and birth, suggesting these mice may provide a unique opportunity to inform on the maternal causes of stillbirth. The onset of IUGR, which was found to be symmetrical in nature, was established by e15.5 preceding the majority of fetal death. During pregnancy, a materno-fetal dialogue directs and responds to changes in gene expression to give rise to the placenta and adapt the maternal physiology. Defects in these processes may result in reduced growth and/or fetal death and were examined in Pabp4-/- mice to shed light on the mechanistic basis of these related phenotypes. Fetal to placental (F:P) weight ratio, whose changes can be indicative of placental insufficiency or placental adaptation in an attempt to aid fetal growth, was found to be increased in Pabp4-/- dams at e15.5 and e18.5 due to the presence of IUGR fetuses with placentas of normal weight. Consistent with this observation, placental volume was unchanged at e18.5. Total placental weight and volume alone fails to discriminate potential differences in the individual placental zones which include the labyrinth zone, where materno-fetal gas and nutrient exchange occur; the junctional zone, which has endocrine functions including those that promote maternal adaptation; and the decidua basalis, derived from the maternal endometrium and is the site of trophoblast invasion and maternal vascular remodelling in early pregnancy. Therefore, volumetric analysis of these zones and the maternal blood spaces, which transcend the decidua basalis and junctional zone, was undertaken. This showed no change in the maternal blood spaces or the labyrinth, the latter being the zone whose size is most frequently altered in IUGR. Critically however, the size of the maternally-derived decidua basalis was increased with a concurrent decrease in the size of the junctional zone. These morphological changes may play a causative role either through directly affecting placental function and/or by the reduced junctional zone failing to promote appropriate maternal adaptation. Alternatively, they may reflect compensatory adaptations to a primary defect elsewhere in the mother. Complementing these morphological studies, functional studies were undertaken: remodelling of maternal vasculature and the resistance index of vessels delivering blood to the fetus were assessed; as was delivery of nutrients to the fetus (measured by fetal glucose); and systemic maternal adaptations (maternal hormonal profile, circulating glucose levels and organ weights). Uterine, umbilical and decidual spiral arteries were examined, but displayed no apparent differences suggestive of normal blood supply to the fetus. However fetal blood glucose was reduced suggesting a reduced delivery of nutrients important for fetal growth. This was not due to lower circulating maternal blood glucose levels, and mRNA levels of the placental glucose transporters Glut-1 and Glut-3 were not reduced but upregulated, suggestive of an attempt to compensate for reduced fetal glucose. Furthermore, upregulation of at least one system A amino acid transporter mRNA, Snat-2, was observed. The maternal physiological state of PABP4-deficient dams showed deviations in some organ weights (e.g. spleen weight is reduced at e13.5 and e15.5) and the levels of some circulating hormones (e.g. estradiol is deceased whereas progesterone is increased at e18.5). However, future work will be required to determine which, if any, of these changes are primary defects rather than downstream consequences and to identify which mis-regulated mRNAs/pathways within in the materno-fetal dialogue underlie the phenotype. Taken together, my results suggest that the regulation of mRNA translation/stability by PABP4 is critical to achieving the correct pattern of gene expression within the materno-fetal dialogue to enable appropriate placentation and maternal adaptation. Furthermore, my results suggest that Pabp4-/- mice provide a unique opportunity to further understand the maternal causes of a spectrum of related pregnancy complications including IUGR, late miscarriage and stillbirth.

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Huber, Hillary. "Aggressive Behavioral Phenotype in Intrauterine Growth Restricted (IUGR) Baboons Exposed to Moderate Nutrient Restriction Early in Development." OpenSIUC, 2014. https://opensiuc.lib.siu.edu/dissertations/824.

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The thrifty phenotype hypothesis proposes reduced nutrition alters the trajectory of development of metabolic regulatory systems to produce a phenotype better fitted to an environment of decreased later-life nutrient availability. Because organisms have physiological mechanisms for coping with poor nutrition, they may have sociobehavioral mechanisms as well. Aggressive behavior, especially in the context of feeding competition, may be advantageous in such environments. There could be an association between aggression and intrauterine growth restriction (IUGR), which can result from low maternal food intake during pregnancy. The main hypotheses of this study are [1] IUGR offspring demonstrate higher rates of aggressive behavior and [2] IUGR offspring attain higher ranks. Behavioral observations were conducted on 22 juvenile baboons (Papio sp., ages 3-5 yrs) living in groups. Male IUGR (n = 4) and female IUGR (n = 5) were offspring of mothers fed 70% the same feed eaten by control (CTR) mothers in pregnancy and lactation. CTR males (n = 8) and CTR females (n = 5) were offspring of mothers fed ad libitum. Some authorities recommend this moderate level of dietary restriction for health and longevity. Offspring have not experienced dietary restriction since weaning. IUGR, compared to CTR, showed significantly increased rates of aggressive behavior, especially threat displays. Differences were more dramatic in males than in females. IUGR baboons performed the affiliative display behaviors lipsmack and chatter at elevated rates too, perhaps to counteract the effects of increased aggressive displays. IUGR females exhibited increased rates of stereotypical chewing behavior, while IUGR males exhibited decreased rates of play behavior, possibly indicating elevated anxiety levels. There was only limited support for condition-based differences in rank. Elevated rates of aggression in IUGR baboons may reflect an aggressive behavioral phenotype that enhances fitness by improving access to resources. Alternatively, they could be a non-adaptive result of neurodevelopment with a potentially negative impact on fitness. Unraveling the dynamic relationship between experiences and development is essential for understanding how phenotypes are formed. This will improve the ability of mothers to assess benefits of different nutritional strategies, leading to healthier individuals not just during growth and development, but throughout life.

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Bahr, Brigham L. "Different Expression of Placental Pyruvate Kinase M2 in Normal, Preeclamptic, and Intrauterine Growth Restriction Pregnancies." BYU ScholarsArchive, 2014. https://scholarsarchive.byu.edu/etd/3901.

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This thesis will be organized into two chapters discussing the placental expression of two proteins, pyruvate kinase M2 (PKM2) and heat shock protein 27 (HSP 27), in human placentas. Understanding the mechanisms of placental metabolism in healthy and diseased placentas helps us understand how placenta disorders occur and how we can treat these disorders. The goal is to investigate these proteins to gain an understanding of their roles in placental disorders and help decrease maternal and fetal mortality rates. Chapter one covers the background of pyruvate kinase M2 (PKM2) in cancer and embryonic tissues, and the expression of PKM2 in the human placenta. Cancer PKM2 has been studied extensively, but little is know about the role of placental PKM2. Expression of PKM2 is confirmed in normal human placenta samples and described in preeclamptic and intrauterine growth restriction (IUGR) affected human placentas. Proteins associated with elevated PKM2 in cancer are also associated with elevated PKM2 in human placentas. Comparing normal and diseased placenta samples helps understand the similarities between cancer PKM2 and placental PKM2. Understanding the mechanisms of placental metabolism and PKM2 expression in the human placenta will clarify how the placenta is affected by preeclampsia and IUGR and the role placental PKM2 plays in each of these diseases. Chapter two will cover a paper that I wrote on the expression of phosphorylated heat shock protein 27 (HSP27) in the human placenta. Heat shock proteins are involved in the stress response and help inhibit apoptosis. The object of the study was to look for correlations between p-HSP27 and apoptosis in human and ovine placenta samples. P-HSP27 was quantified in human placenta samples and in placenta sampled collected from ovine models. Pregnant control and hyperthermic sheep models were used to quantify expression of p-HSP27 across gestation. This study showed similarities between human IUGR and our ovine IUGR model, suggesting a link between decreased p-HSP27 and increased apoptosis in IUGR.

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Yunusova, Roza. "Effects of Maternal Nutrition, Intrauterine Growth Restriction (IUGR), and Estrogen (E2) Supplementation on Placental and Fetal Intestinal Growth and Development in Sheep." Thesis, North Dakota State University, 2012. https://hdl.handle.net/10365/26539.

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The placenta and fetal intestines are two key nutrient transport organs that sustain and nurture growing fetus. Insufficient placental development and consequently inadequate fetal nutrient supply can lead to IUGR resulting in low birth weight offspring. Our experimental objectives were to investigate the effects of elevated maternal nutrition, IUGR, and E2 supplementation during mid-gestation (in an attempt to rescue IUGR offspring) on placental and fetal intestinal cell proliferation, angiogenic gene expression, and vascularity. Limited responsiveness in placental development and vascularization to E2 supplementation was observed, likely due to inappropriate timing or dose of E2. However, maternal E2 supplementation increased fetal small intestinal length and GUCY1b3 mRNA expression, suggesting that E2 supplementation has positive effects on IUGR fetal intestinal growth. In conclusion, understanding molecular mechanisms associated with IUGR and possible effects of E2 supplementation in rescuing IUGR may lead to enhanced human health and livestock production efficiency.

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Iglesias, Platas Isabel. "Intrauterine Growth Restriction (IUGR) and imprinted gene expression in the placenta: Role of PLAGL1 and analysis of the 6q24.2 Region." Doctoral thesis, Universitat de Barcelona, 2012. http://hdl.handle.net/10803/109049.

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BACKGROUND: Fetal growth is a complex process which depends on nutrient and oxygen availability and transport from the mother to the fetus across the placenta. This involves hormones and growth factors as well as maternal and fetal genes. The failure of the fetus to reach his or her full potential for growth is called Intrauterine Growth Restriction (IUGR) and implies risks for adverse short‐ and long‐ term outcomes. Imprinted genes are a specific subset of genes that display, in mammals and flowering plants, monoallelic expression depending on the parental origin of the allele. The regulation of imprinted expression depends on epigenetic mechanisms, a subset of heritable marks that have the ability to regulate DNA functions without altering its sequence. Imprinted genes tend to cluster in the genome due to coordinated regulation through Imprinting Control Centers, usually in the form of Differentially Methylated Regions between the paternally and maternally inherited alleles. Studies in both animals and humans as well as imprinting syndromes have uncovered a role for this group of genes in prenatal growth. Two imprinted genes (PLAGL1 and HYMAI) have been described in the 6q24 locus. Genetic and epigenetic defects in this region relate to the Transient Neonatal Diabetes Mellitus 1 phenotype, including severe growth restriction. We aimed to study the involvement of this region in non‐syndromic IUGR. PARTICIPANTS AND METHODS: One hundred placental samples from a cohort of healthy term singletons, fetal tissues from fifty‐four first trimester terminations and one hundred placental samples from healthy and complicated pregnancies of different gestational ages were used to analyze the role of the 6q24 region in normal fetal growth and IUGR, respectively. Relevant clinical data was obtained after informed consent. The methylation status of the 6q24 CpG islands was studied by array technology and bisulfite sequencing in normal term placenta and in first trimester fetal tissues. Methylation levels in the PLAGL1 DMR in healthy and IUGR placentas were compared by pyrosequencing. Allelic origin of expression was assessed by heterozygous DNA/cDNA SNP analysis. Levels of expression of imprinted transcripts were analyzed by qRT‐PCR. RESULTS: PLAGL1 P1, HYMAI and two newly described PLAGL1 isoforms (P3 and P4) were the only transcripts subjected to genomic imprinting in the investigated 6q24 region. Correspondingly, the CpG island associated to the P1 promoter was the only differentially methylated region. There was no correlation between PLAGL1 expression in the placenta and fetal size in uneventful pregnancies. In placentas from IUGR gestations, expression of HYMAI was significantly higher than in those from normally grown fetuses. Levels of expression of PLAGL1 were lower in IUGR and correlated positively and significantly with the presence of IUGR in placentas from girls, but not boys. These changes in expression were not mediated by Loss of Imprinting or abnormalities in the levels of methylation of the promoter‐associated DMR, but possibly by a change in regulatory posttranscriptional mechanisms, as suggested by the loss of correlation of PLAGL1 P1 and HYMAI expression in IUGR. CONCLUSIONS: Imprinted expression in the 6q24 region is limited to the PLAGL1/HYMAI locus, maybe due to demarcation of this region by CTCF boundaries. Intrauterine Growth Restriction is associated to abnormalities in expression of PLAGL1 and HYMAI in the placenta, which are not due to LOI or methylation changes.

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Fayyad, Abdalla Mustafa. "The role of soluble FMS-like tyrosine kinase (sFLT1) and FAS associated proteins in pregnancies complicated by preeclampsia and intrauterine growth restriction (IUGR)." Thesis, Queen Mary, University of London, 2005. http://qmro.qmul.ac.uk/xmlui/handle/123456789/1750.

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Current thinking suggests that preeclampsia is associated with activation of the maternal vascular endothelium in response to factors released from the placenta due to placental hypoxia. Failure of physiological modification of spiral arteries due to impaired trophoblast invasion results in a several-fold increase in the risk of developing pre-eclampsia and/or (IUGR). The defect behind impaired trophoblast invasion is not fully explained and the aetiological factor(s) linked with the development of pre-eclampsia, compared to normotensive IUGR, is not known. In this thesis, I examined placental and serum levels of fms-like tyrosine kinase I (sFltl) and placental growth factor (PIGF), as mediators of angiogenesis, and Fas and FasL, as mediators of apoptosis, in three groups; preeclampsia, normotensive IUGR and controls who had abnormal mid-trimester uterine artery Doppler. Uterine artery Doppler flows were examined in 553 women at 24 weeks. 97 of them had abnormal uterine artery Doppler flow and were enrolled in this study. 86 women were followed up; among them eight women developed preeclampsia and seven developed normotensive IUGR. Umbilical artery Doppler examination 24 hours before delivery in both groups, showed significantly lowered resistance indices in the preeclampsia compared to the normotensive IUGR group. I examined placental and serum levels of fms-like tyrosine kinase I (FIt I) and Placental Growth Factor (PIGF) in three groups. Soluble FItI acts as an antagonist for both Vascular Endothelial Growth Factor (VEGF) and PIGF. Placental FIt 1 and serum sFlt 1 were higher and serum PIGF was lower in the preeclampsia group compared to the other two groups. This could be responsible for the systemic manifestations of preeclampsia. This dysregulation in serum sFltl and PIGF was found as early as 24 weeks in pregnancies with abnormal uterine artery Doppler examination. The normotensive IUGR group had significantly elevated serum sFlU compared to controls. This could be due to an element of placental hypoxia in the IUGR group. To investigate the in-vivo effect of sFltl on impaired placental angiogenesis and trophoblast invasion, I examined the correlations between uterine artery Doppler resistance indices and serum sFIU and PIGF at 24 weeks. Significant correlations were found between these markers and uterine artery Doppler pulsatility index (pn and resistance index (Rn on both the placental and non-placental sides at 24 weeks. Fas and Fas ligand (FasL) are membrane proteins that mediate cellular apoptosis, and recently were related to cellular growth and migration. Using western blotting and immunohistochemistry, placental expression of Fas (western blotting) and (FasL) (immunohistochemistry) was assessed in the three study groups. No differences in placental Fas or Fas ligand were found between the groups. In addition, serum levels of Fas and FasL were measured at 24 weeks and within 24 hours of delivery in the same groups. Serum Fas was not different between the three study groups at 24 weeks and within 24 hours of delivery. Serum FasL was below the kit's detection threshold in the samples studied. In conclusion, placental FlU and its soluble form sFltl seem to play an important role in the pathophysiology of preeclampsia. In addition, sFltl correlated positively with the severity of impaired trophoblast invasion and could playa central role in blocking placental angiogenesis in these pregnancies. This needs further evaluation. Fas and FasL do not seem to have a role In impaired placentation and development of preeclampsia and IUGR.

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Diderholm, Barbro. "Perinatal Energy Substrate Metabolism : Glucose Production and Lipolysis in Pregnant Women and Newborn Infants with Particular Reference to Intrauterine Growth Restriction (IUGR)." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4842.

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Kimball, Rebecca Lutz. "The Role of Hypoxia on Pyruvate Kinase M2, mammalian Target of Rapamycin, Mitochondrial Function, and Cell Invasion in the Trophoblast." BYU ScholarsArchive, 2016. https://scholarsarchive.byu.edu/etd/5723.

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This thesis will be organized into two chapters discussing the role of hypoxia in the human placenta. The goal of this thesis is to characterize pyruvate kinase M2, mammalian target of rapamycin, mitochondrial function, and cell invasion in hypoxic conditions in the trophoblast. Understanding the mechanisms of placental metabolism can lead to further treatments for placental diseases. Chapter one covers the background of intrauterine growth restriction, hypoxia, placental metabolism, and pyruvate kinase M2 (PKM2). Little is currently understood about the role of the mitochondria in placental diseases. Expression of PKM2, trophoblast cell invasion, and mitochondrial function is shown to be inhibited by hypoxia. PKM2 inhibition decreases trophoblast cell invasion and nuclear expression of PKM2, but increases mitochondrial function. Studying how hypoxia affects the placenta during placental diseases can help clarify the mechanisms by which these diseases occur. Chapter two further characterizes the background of intrauterine growth restriction and hypoxia. It also covers the background of mammalian target of rapamycin. The objective of this chapter was to assess activated mTOR in the trophoblast in hypoxia. Decreased placental and fetal weights, as well as trophoblast cell invasion were observed in hypoxia. A decrease in the activation of mTOR was also found in the hypoxic placenta. This study could provide insight into the physiological relevance of the pathways and could be targeted to help alleviate placental diseases.

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Hennig, Maria. "The role of the mTOR pathway and amino acid availability for pre- and postnatal cardiac development, growth and function." Doctoral thesis, Humboldt-Universität zu Berlin, Lebenswissenschaftliche Fakultät, 2015. http://dx.doi.org/10.18452/17287.

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Die Entwicklung eines Embryos und Fetus beeinflusst die Anfälligkeit für kardiovaskuläre Erkrankungen im weiteren Verlauf des Lebens entscheidend. Zugrundeliegende Mechanismen sind jedoch weitestgehend unbekannt. Unter Zuhilfenahme eines neuen Mausmodells für intrauterine kardiale Wachstumsretardierung zielt die vorliegende Dissertation auf die Identifikation adaptiver Wachstumsmechanismen ab, welche die Anpassung der Organgröße und die Aufrechterhaltung einer normalen Herzfunktion ermöglichen. Vielzählige Gene des Aminosäure (AS)-Metabolismus und der Proteinhomeostase zeigten eine vermehrte Expression in neugeborenen Mausherzen nach gestörter Embryonalentwicklung. Es wurde angenommen, dass sowohl die AS-Verfügbarkeit als auch die Aktivität der mechanistic target of rapamycin (mTOR) Signalkaskade entscheidend für eine normale Herzentwicklung und postnatales kompensatorisches Wachstum sind. Der mTOR Komplex 1 (mTORC1) wurde in prä- und perinatalen Mäusen mittels Rapamycin-Behandlung trächtiger Weibchen inhibiert. Die Auswirkungen einer prä- und postnatalen AS-Restriktion wurden anhand einer Niedrigproteindiät untersucht. Rapamycin-behandelte Neugeborene zeichneten sich durch vermindertes Gesamtwachstum sowie Entwicklungsverzögerung aus. Dabei war die kardiale Entwicklung besonders betroffen. Kardiale Proliferationsraten waren nicht verändert, die verminderte Herzgröße wurde jedoch auf eine verringerte Kardiomyozytengröße sowie eine erhöhte Apoptoserate zurückgeführt. Die intrauterine AS-Restriktion wurde überraschend gut von den Mausherzen toleriert. Zusammenfassend konnte gezeigt werden, dass die mTOR Signalkaskade essentiell für eine normale Herzentwicklung sowie kompensatorisches kardiales Wachstum ist. Darüber hinaus stellt die pränatale Rapamycin-Behandlung möglicherweise ein neues Modell der intrauterinen Wachstumsretardierung dar, welches Untersuchungen von Programmierungs-Mechanismen vor allem während der fötalen und perinatalen Herzentwicklung ermöglicht.
Intrauterine development influences the susceptibility to cardiovascular disease in adulthood, although the underlying molecular mechanisms are vastly unknown. Utilizing a new mouse model of impaired heart development, this thesis aims at identifying pre- and postnatal adaptive growth mechanisms to restore organ size and allow normal cardiac function. Unbiased functional annotation of genes differentially expressed in neonatal hearts after impaired intrauterine development revealed numerous gene clusters involved in amino acid (AA) metabolism and protein homeostasis. It was hypothesized that both AA availability and mechanistic target of rapamycin (mTOR) pathway activation are crucial for normal heart development and compensatory cardiac growth. mTOR complex 1 (mTORC1) was inhibited in fetal and neonatal mice by rapamycin treatment of pregnant dams. The effects of pre- and postnatal AA restriction were studied by feeding dams a low protein diet (LPD) throughout pregnancy and keeping the offspring on LPD postnatally. Rapamycin treated neonates were characterized by overall growth restriction and developmental delay, where cardiac development was especially affected (reduction of heart size, weight and heart weight to body weight ratio, severe thinning and noncompaction of the ventricular myocardium as well as immature myocardial morphology). While proliferation rates were unaffected, the reduced neonatal heart size was attributed to decreased cardiomyocyte size and increased apoptosis. Strikingly, the murine heart appeared to be surprisingly resistant to intrauterine AA restriction. In conclusion, the data revealed mTOR being essential for normal as well as compensatory cardiac development and growth. Moreover, prenatal rapamycin treatment might represent a new model of intrauterine growth restriction, which potentially allows the investigation of developmental programming mechanisms within the heart particularly in the fetal and neonatal phase of development.

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Zhu, Haibo. "Muscle Growth and Development in Intrauterine Growth Restricted Pigs." Diss., Virginia Tech, 2015. http://hdl.handle.net/10919/72883.

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Intrauterine growth restriction causes impaired growth and development of mammalian fetus, and leads to long-term negative effect on postnatal growth. Among domestic animals, pigs exhibit the most severe naturally occurring IUGR and reduced postnatal muscle growth. The objectives of this research project were to: 1) determine muscle stem cell characteristics in IUGR pigs; 2) determine how intrauterine growth restriction alters protein deposition in skeletal muscle; 3) investigate whether branched-chain amino acids (BCAA) are able to enhance protein synthesis in intrauterine growth restricted (IUGR) pig muscle. Newborn piglets were considered normal body weight (NBWT) or IUGR when birth weight was within ± 0.5 SD and -2 SD of litter average respectively. Muscle satellite cell numbers, believed to be the major nuclei source for postnatal muscle growth, were lower in newborn IUGR pigs which could result in reduced muscle hypertrophy potential. In addition, cultures derived from IUGR muscle satellite cells had a lower fusion percentage. Fewer satellite cells and impaired differentiation ability may contributor to impaired muscle growth in these pigs. Protein synthesis rate was significantly lower in IUGR pig hindquarter in the first hour after feeding, but BCAA supplementation had no effect on protein synthesis in IUGR pigs. Further, eukaryotic translation initiation factor 4E (eIF4E) expression is down regulated in IUGR pig muscle. These results suggest that impaired translation initiation may provide a plausible explanation for the lower protein synthesis rates observed in IUGR pigs. Overall, reduced muscle stem cell number and changes in their activity, as well as impaired translation initiation may be important explanations for compromised postnatal muscle growth in intrauterine growth restricted pigs.
Ph. D.

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Östlund, Eva. "Growth factors and vasoactive substances in intrauterine growth restriction and preeclampsia /." Stockholm, 2001. http://diss.kib.ki.se/2001/91-628-5046-6/.

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Lassala, Arantzatzu Leticia. "Arginine and fetal growth in ovine models of intrauterine growth restriction." [College Station, Tex. : Texas A&M University, 2008. http://hdl.handle.net/1969.1/ETD-TAMU-3238.

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Crispi, Brillas Fàtima. "Fetal progamming of cardiovascular dysfunction in intrauterine growth restriction." Doctoral thesis, Universitat de Barcelona, 2009. http://hdl.handle.net/10803/2276.

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BACKGROUNDFetal growth restriction (FGR), with a prevalence of 5-10% in newborns, is associated with increased cardiovascular mortality in adulthood, but the pathophysiological links of this relationship are only partially understood. The main hypothesis of this thesis was that FGR induces primary cardiac dysfunction and remodelling in utero that persists postnatally and leads to increased cardiovascular risk in adulthood. METHODSCardiovascular function was assessed in a cohort of FGR fetuses and correlated to the severity stages of FGR, presence of preeclampsia and also perinatal data in order to evaluate its potential utility in the clinical management of these fetuses. Finally, cardiac and vascular function was also assessed in childhood.RESULTSIn utero, FGR fetuses showed signs of subclinical cardiac dysfunction measured by echocardiography (increased E/A ratios and isovolumic times with normal cardiac output) from early stages. Cardiac dysfunction deteriorated further with the progression of fetal compromise, together with the appearance of biochemical signs of cell damage (increased heart-fatty acid binding protein concentrations in cord blood). Preeclampsia per se was not associated to cardiac function in FGR fetuses. Cardiac function parameters, such as ductus venosus and myocardial performance index, were independently associated with perinatal death in preterm FGR. Therefore, a combination cardiac parameters may be useful in the clinical management of preterm FGR by stratifying the estimated probability of death. Children with FGR showed changes in cardiac shape (more globular morphology), subclinical cardiac dysfunction (increased heart rate and reduced stroke volume and myocardial peak velocities) and vascular remodelling (increased blood pressure and carotid intima-media thickness). CONCLUSIONSFGR present cardiovascular dysfunction in utero that persists postnatlly. These findings suggest that fetal growth restriction induces primary cardiac changes which could explain the increased predisposition to cardiovascular disease in adult life. Given its high prevalence in the general population, this might have to be taken into account in assessing cardiovascular risk factors and treatment.
INTRODUCCIÓNEl retaso de crecimiento intrauterino (CIR), con una prevalencia del 5-10% de los recién nacidos, se asocial a un aumento de la mortalidad cardiovascular en vida adulta, pero la fisiopatología de esta correlación aun es incierta. La principal hipótesis de esta tesis fue que el CIR induce una disfunción y remodelado cardiovascular primario in útero que después persiste en vida postnatal y condiciona un aumento del riesgo cardiovascular en vida adulta.MÉTODOSEn una cohorte de fetos CIR se evaluó la función cardiovascular y se correlacionó con el grado de severidad del CIR, la presencia de preeclampsia y también los resultados perinatales, para poder evaluar su potencial utilidad en el manejo clínico de estos fetos. Finalmente, la función cardiovascular también fue evaluada postnatalmente.RESULTADOSEn útero, los fetos CIR mostraron signos de disfunción cardiaca subclínica medida mediante eco cardiografía (aumento de los ratios E/A i tiempos isovolumétricos, con gasto cardíaco normal) des de estadios iniciales de severidad. La función cardiaca mostró un deterioro progresivo con el aumento de severidad del CIR, a la vez que aparecieron signos bioquímicos de daño miocárdico en estadios finales de deterioro (aumento de los niveles de heart-fatty acid binding proteins en sangre de cordón). La preeclampsia per se no mostró asociación con el grado de disfunción cardiaca. Algunos parámetros de función cardiaca fetal, como el ductus venoso y el índice de rendimiento miocárdico, mostraron una asociación independiente con la mortalidad perinatal en los casos de CIR pretérmino. A nivel postnatal, los niños con antecedente de CIR mostraron cambios en la morfología cardiaca (más globular), disfunción cardiaca subclínica (aumento de la frecuencia cardiaca, y reducción del volumen de eyección y velocidades miocárdicas) y remodelación vascular (aumento de la presión arterial y grosor de las carótidas).CONCLUSIONESLos casos de CIR presentan una disfunción cardiovascular in útero que persiste postnatalmente. Los resultados sugieren que el CIR induce cambios cardiacos primarios que podría explicar la mayor predisposición a patología cardiovascular en vida adulta.

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Guitart, Mampel Mariona. "Mitochondrial implication in intrauterine growth restriction and cardiovascular remodelling." Doctoral thesis, Universitat de Barcelona, 2018. http://hdl.handle.net/10803/668102.

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Intrauterine growth restriction (IUGR) is an obstetric complication characterized by placental insufficiency and secondary cardiovascular remodeling that may lead to cardiomyopathy in adulthood. Its etiology and potential therapeutics are poorly understood. Mitochondrial bioenergetics pathways are mainly regulated by nuclear effectors such as sirtuins and are essential for embryonic development and cardiovascular function. Members of our group developed a rabbit model of IUGR and cardiovascular remodeling, in which heart, mitochondrial alterations were observed by microscopic and transcriptomic analysis. We aimed to evaluate if such alterations are translated at a functional mitochondrial level to establish the ethiopathology and potential therapeutic targets for this obstetric complication. For that aim, heart and placenta from the rabbit model was included as well as placenta from human pregnancies together with maternal and neonatal blood. At delivery, peripheral blood and cord blood mononuclear cells (PBMC and CBMC, respectively) were isolated. For the mitochondrial characterization, we assessed: oxygen consumption of the mitochondrial respiratory chain (MRC) by polarography using endogen cellular substrates and substrates for complex I. Also, enzymatic activity of complex I, II, IV, I+III and II+III of MRC, subunit protein expression of some of the MRC complexes (CII-SDHA, CII-SDHB and CIV-COX5A), Coenzyme Q levels, mitochondrial content (through citrate synthase activity, Tom20 expression or mitochondrial DNA (mtDNA) levels), oxidative stress (by lipid peroxidation and SOD2 activity) and ATP levels. Finally, Sirtuin 3 protein expression was measured by Western Blot. In the IUGR offspring from the rabbit model, we found a significant decrease of MRC function: enzymatic activity of complexes II, IV and II+III in IUGR hearts (p<0.05) and complexes II and II+III in IUGR placentas (p<0.05 and p<0.01, respectively). This was occurring with a not significant reduction in CI-stimulated oxygen consumption in both tissues and a significant decrease of complex II SDHB subunit expression in placenta (p<0.001). Additionally, levels of mitochondrial content, Coenzyme Q and cellular ATP were conserved. Lipid peroxidation significantly decreased in IUGR hearts (p<0.001), but not significantly increased in IUGR placentas. Finally, Sirtuin3 protein expression significantly increased in IUGR hearts (p<0.05). In human pregnancies, IUGR placental tissue showed an altered mitochondrial phenotype with a significant decrease of CI-stimulated oxygen consumption (p<0.05) and MRC complex I enzymatic activity (p<0.05). The enzymatic activities of the others MRC complexes and CS were preserved. In blood cells, conserved cellular oxygen consumption and trends to decrease CI-stimulated oxygen consumption was observed in maternal PBMC, but trends to decrease both cellular and CI-stimulated oxygen consumption were evidenced in neonatal CBMC, pointing out that IUGR newborns presented higher mitochondrial deficits compared to mothers. Moreover, no differences in MRC enzymatic activities in maternal PBMC or in neonatal CBMC were observed. Conserved CS activity was present in maternal PBMC but was significantly decreased in neonatal CBMC. So, in front of unaltered mtDNA levels in neonatal CBMC, alterations in neonatal CS would be related to Krebs cycle imbalances rather than to mitochondrial content. All these changes did not affect oxidative stress or ATP production in any tissue. Finally, Sirtuin3 protein expression also showed a relevant increase in human IUGR placenta (p=0.05). The relevance of this thesis relies on the description of mitochondrial impairment in the offspring of a rabbit model of IUGR but also in newborns from pregnancies complicated by IUGR. This mitochondrial imbalance is widely present in the different studied tissues, including the heart and the placenta from the rabbit model and the placenta and neonatal blood cells from human pregnancies. The mitochondrial characterization of this obstetric complication could help to greater understand the pathophysiologic mechanisms underlying cardiac remodelling and IUGR.
Els nounats amb creixement intrauterí restringit (CIR) desenvolupen un remodelat cardiovascular fetal i idiopàtic que pot portar a cardiopatia durant l’etapa adulta. La bioenergètica mitocondrial, essencial pel desenvolupament embrionari i la funció cardíaca, està regulada per diferents proteïnes, entre elles la Sirtuina 3. Es tracta d’una proteïna deacetilasa d’alt interès terapèutic, ja que es pot modular a través de la dieta. Els cors de cries amb CIR d’un model animal de conill mostren alteracions transcriptòmiques i ultraestructurals a nivell mitocondrial. L’objectiu de l’estudi ha sigut determinar la implicació d’una possible disfunció mitocondrial i de la Sirtiuna 3 en el CIR. Les troballes demostren una alteració mitocondrial de la cadena respiratòria en el cor i la placenta de les cries amb CIR del model animal (sobretot a nivell de l’activitat enzimàtica dels complexes II i IV; p<0.05) i també a la placenta de gestants humanes amb CIR (especialment del complex I; p<0.05). A més a més, aquesta alteració mitocondrial s’ha evidenciat en els nounats amb CIR a través de la reducció de l’activitat de l’enzim citrat sintasa (p<0.05), suggerint alteracions a nivell del cicle de Krebs. L’ATP cel·lular i el dany oxidatiu es troba preservat en tots els teixits estudiats, excepte en el cor de les cries del model animal de CIR, on el trobem disminuït significativament (p<0.001). Aquest desajust mitocondrial va acompanyat d’un augment significatiu de l‘expressió de la proteïna Sirtuina 3 en el cor de les cries del model animal de CIR i també a la placenta de les gestants humanes amb CIR (p<0.05). Les troballes derivades d’aquest estudi permeten associar la disfunció mitocondrial al desenvolupament del CIR i el remodelat cardiovascular associat, donant lloc al disseny d’estratègies dietètiques destinades a modular l’esmentat desbalanç bioenergètic a través de la regulació de la Sirtuina 3.

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15

Crispi, Brillas Fàtima. "Fetal programming of cardiovascular dysfunction in intrauterine growth restriction." Doctoral thesis, Universitat de Barcelona, 2009. http://hdl.handle.net/10803/2276.

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BACKGROUND

Fetal growth restriction (FGR), with a prevalence of 5-10% in newborns, is associated with increased cardiovascular mortality in adulthood, but the pathophysiological links of this relationship are only partially understood. The main hypothesis of this thesis was that FGR induces primary cardiac dysfunction and remodelling in utero that persists postnatally and leads to increased cardiovascular risk in adulthood.

METHODS

Cardiovascular function was assessed in a cohort of FGR fetuses and correlated to the severity stages of FGR, presence of preeclampsia and also perinatal data in order to evaluate its potential utility in the clinical management of these fetuses. Finally, cardiac and vascular function was also assessed in childhood.

RESULTS

In utero, FGR fetuses showed signs of subclinical cardiac dysfunction measured by echocardiography (increased E/A ratios and isovolumic times with normal cardiac output) from early stages. Cardiac dysfunction deteriorated further with the progression of fetal compromise, together with the appearance of biochemical signs of cell damage (increased heart-fatty acid binding protein concentrations in cord blood). Preeclampsia per se was not associated to cardiac function in FGR fetuses. Cardiac function parameters, such as ductus venosus and myocardial performance index, were independently associated with perinatal death in preterm FGR. Therefore, a combination cardiac parameters may be useful in the clinical management of preterm FGR by stratifying the estimated probability of death. Children with FGR showed changes in cardiac shape (more globular morphology), subclinical cardiac dysfunction (increased heart rate and reduced stroke volume and myocardial peak velocities) and vascular remodelling (increased blood pressure and carotid intima-media thickness).

CONCLUSIONS

FGR present cardiovascular dysfunction in utero that persists postnatlly. These findings suggest that fetal growth restriction induces primary cardiac changes which could explain the increased predisposition to cardiovascular disease in adult life. Given its high prevalence in the general population, this might have to be taken into account in assessing cardiovascular risk factors and treatment.
INTRODUCCIÓN

El retaso de crecimiento intrauterino (CIR), con una prevalencia del 5-10% de los recién nacidos, se asocial a un aumento de la mortalidad cardiovascular en vida adulta, pero la fisiopatología de esta correlación aun es incierta. La principal hipótesis de esta tesis fue que el CIR induce una disfunción y remodelado cardiovascular primario in útero que después persiste en vida postnatal y condiciona un aumento del riesgo cardiovascular en vida adulta.

MÉTODOS

En una cohorte de fetos CIR se evaluó la función cardiovascular y se correlacionó con el grado de severidad del CIR, la presencia de preeclampsia y también los resultados perinatales, para poder evaluar su potencial utilidad en el manejo clínico de estos fetos. Finalmente, la función cardiovascular también fue evaluada postnatalmente.

RESULTADOS

En útero, los fetos CIR mostraron signos de disfunción cardiaca subclínica medida mediante eco cardiografía (aumento de los ratios E/A i tiempos isovolumétricos, con gasto cardíaco normal) des de estadios iniciales de severidad. La función cardiaca mostró un deterioro progresivo con el aumento de severidad del CIR, a la vez que aparecieron signos bioquímicos de daño miocárdico en estadios finales de deterioro (aumento de los niveles de heart-fatty acid binding proteins en sangre de cordón). La preeclampsia per se no mostró asociación con el grado de disfunción cardiaca. Algunos parámetros de función cardiaca fetal, como el ductus venoso y el índice de rendimiento miocárdico, mostraron una asociación independiente con la mortalidad perinatal en los casos de CIR pretérmino. A nivel postnatal, los niños con antecedente de CIR mostraron cambios en la morfología cardiaca (más globular), disfunción cardiaca subclínica (aumento de la frecuencia cardiaca, y reducción del volumen de eyección y velocidades miocárdicas) y remodelación vascular (aumento de la presión arterial y grosor de las carótidas).

CONCLUSIONES

Los casos de CIR presentan una disfunción cardiovascular in útero que persiste postnatalmente. Los resultados sugieren que el CIR induce cambios cardiacos primarios que podría explicar la mayor predisposición a patología cardiovascular en vida adulta.

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16

Eixarch, Roca Elisenda. "Brain reorganization in an experimental model of intrauterine growth restriction." Doctoral thesis, Universitat de Barcelona, 2011. http://hdl.handle.net/10803/78921.

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1.- INTRODUCTION Intrauterine growth restriction (IUGR) due to placental insufficiency affects 5-10% of all pregnancies. This condition is a risk factor for brain damage after birth and cognitive disorders later in childhood. The pathophysiological pathways leading to adverse neurodevelopmental outcome remain poorly understood. The use of animal models is essential to advance in the understanding of brain injury in IUGR. 2.- OBJECTIVE To develop a suitable experimental model of IUGR in fetal rabbits, in order to conduct a detailed description of the neurostructural brain abnormalities associated with this disease and their neurobehavioral correlates. 3.- MATERIAL AND METHODS P1: Comparison of two experimental models of IUGR: undernutrition versus selective ligature of uteroplacental vessels Prenatal induction of IUGR at 25D by means of a surgical protocol or hiponutirtion. Comparison of neonatal biometries, mortality and hemodynamic changes. P2: Evaluation of different timings and severity of the intervention Prenatal induction of IUGR at 21/25D by means of a surgical protocol (two proportion of ligature (20-30%(mild) or 40-50%(severe)). Comparison of neonatal biometries, mortality and histological brain changes. P3: Anatomical patterns of brain reorganization induced by IUGR and neurobehavioral correlates. Prenatal induction of IUGR at 25D by means of a surgical protocol. Comparison of neurobehaviour and diffusion related parameters obtained by MRI. 4.- RESULTS P1: Comparison of two experimental models of IUGR: undernutrition versus. selective ligature of uteroplacental vessels Fetal mortality rate in control and undernutrition did not show any difference. On the contrary, the ligature group showed a significantly higher mortality rate. (14.3 vs 5.0 vs 54.2%,p<0,001). Neonatal biometries decreased significantly across the experimental groups. Only ligature group showed significant changes in hemodynamic parameters when compared with control. P2: Efectes del moment i la severitat de la lligadura selectiva There was a linear increase in mortality rates across the experimental groups when ordered by gestational age and severity (Linear-by-linear p<0.001). Neonatal biometries showed a significant linear decrease across the experimental groups at 21D and 25D. Finally, markers of brain damage showed a regional patterns according to severity and onset of IUGR. P3: Anatomical patterns of brain reorganization induced by IUGR and neurobehavioral correlates. Growth restricted pups showed poorer results in all parameters. When VBA analysis was applied, statistically significant differences were found in FA distribution between cases and controls in multiple structures that were correlated with most of neurobehavioral domains. 5.- CONCLUSIONS Selective ligature of uteroplacental vessels in the pregnant rabbit reproduces more closely the features of human IUGR than models based on maternal undernutrition. The gestational age and the proportion of vessels ligated produces gradual changes in mortality and biometrical restriction and different patterns of histological changes in the fetal rabbit brain. Finally, IUGR results in a complex regional pattern of neurostructural differences that correlate with specific neurobehavioral changes in neonatal life.
1) INTRODUCCIÓ La restricció del creixement intrauterí (RCIU) secundaria a la insuficiència placentària afecta un 5-10% de tots els embarassos. Aquesta condició es considera un factor de risc important per el dany cerebral neonatal i els problemes cognitius en la infantesa. El coneixement de les vies fisiopatològiques que condueixen a aquest mal resultat és limitat i per aquest motiu, l’ús dels models animals es essencial per avançar en aquest coneixement. 2) OBJECTIU Desenvolupar un model experimental de RCIU adequat per tal de realitzar una descripció detallada dels canvis estructural cerebrals mitjançant ressonància magnètica i de la seva correlació amb els canvis neuroconductuals. 3) MATERIAL I METODES P1: Model experimental de RCIU: hiponutrició vs lligadura selectiva Conills New-Zealand als 25D de gestació es van incloure en un protocol quirúrgic (lligadura 40-50%) o protocol d’hiponutrició (reducció 70% dieta normal) obtenint 3 grups: a. Fetus RCIU (quirúrgic) b. Fetus RCIU (d’hiponutrició) c. Controls En tot ells es va realitzar la inducció prenatal de RCIU als 25D (quirúrgic/hiponutrició), avaluació ecogràfica prenatal, cesària als 30D de gestació i posterior sacrifici i recol•lecció de mostres P2: Efectes del moment i la severitat de la lligadura selectiva Conills New-Zealand als 21D i 25D de gestació es van incloure en un protocol quirúrgic amb dos graus de restricció (20-30% (lleu) i 40-50% (severa)) obtenint 6 grups: a. Controls 21D b. Fetus RCIU: 21D lleu c. Fetus RCIU: 21D sever d. Fetus RCIU: 25D lleu e. Fetus RCIU: 25D sever f. Controls En tot ells es va realitzar la inducció prenatal de RCIU als 21/25D de gestació (lleu/severa), cesària als 30D, recol•lecció de mostres, tinció S100β i Ki-67 i quantificació de cèl•lules positives. P3: Efectes en la funció i la estructura cerebral de la RCIU en el període neonatal Conills New-Zealand als 25D de gestació es van incloure en un protocol quirúrgic (lligadura 40-50%) obtenint 2 grups: a. Fetus RCIU b. Controls En tot ells es va realitzar la inducció prenatal de RCIU als 25D, cesària als 30D, avaluació neurològica neonatal, sacrifici i recol•lecció de mostres, adquisició de ressonància magnètica i anàlisis dels paràmetres de difusió. 4) RESULTATS P1: Model experimental de RCIU: hiponutrició vs lligadura selectiva La taxa de mortalitat fetal en el grup control d’hiponutrició no va mostrar cap diferència. Per contra, el grup de lligadura va mostrar una taxa de mortalitat significativament més gran (14.3 vs 5.0 vs 54.2%,p<0,001). Les biometries neonatals es van presentar una reducció significativa entre els grups experimentals. La funció cardíaca van presentar un canvi progressiu a través dels grups d’estudi, essent només significatius en el grup de lligadura. P2: Efectes del moment i la severitat de la lligadura selectiva Existeix un augment progressiu i lineal a través dels grups d’estudi de la taxa de mortalitat (p lineal <0,001). Totes les biometries fetal van presentar un descens progressiu i lineal a través del grups d’estudi, tant als 21 com als 25 dies. Els marcadors de dany cerebral van mostrar un partó regional diferent en funció de la gravetat i el moment la RCIU. P3: Efectes en la funció i la estructura cerebral de la RCIU en el període neonatal El grup de RCIU va mostrar pitjors resultats en tots els paràmetres, essent els canvis significatius en els reflexes, tó, locomoció, moviment lineal, distància de pas, reflex a l'alimentació i resposta olfactòria. Mitjançant VBA, es van trobar valors de FA significativament diferents entre casos i controls en varies estructures que també van presentar correlacions tant positives com negatives amb diferents dominis de la neurofunció. 5) CONCLUSIONS La lligadura selectiva dels vasos úter-placentaris reprodueix molt millor els canvis cardiovasculars observats en la RCIU en comparació amb el model d’hiponutrició resultant en un model gradual de la restricció del creixement que produeix diferents patrons de canvis histològics en el cervell fetal. Finalment, la RCIU s'associa a un patró complex de reorganització cerebral que està present en el període neonatal produint alteracions en la funció que es correlacionen amb canvis en la estructura

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17

Tunster, Simon James. "Excess Phlda2 as a mouse model of intrauterine growth restriction." Thesis, Cardiff University, 2009. http://orca.cf.ac.uk/54858/.

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A small fraction of mammalian genes exhibit parent-of-origin specific monoallelic expression. They are expressed from only one allele and this is determined by modifications established in the germline. Approximately 100 imprinted genes have been identified to date. Most imprinted genes are located in discrete clusters and are controlled by shared regulatory elements. Imprinted genes play important roles in regulating embryonic and placental development, with overt growth phenotypes resulting both from loss of expression and from over-expression of imprinted genes. The maternally expressed Phlda2 gene has been implicated in placental development. Loss of expression leads to placentomegaly as a consequence of the disproportionate expansion of the spongiotrophoblast layer. In this study, the consequences of over-expressing Phlda2 and the adjacent Slc22a18 were investigated in four independent lines of transgenic mice driving incrementally increasing doses of the two genes and on two genetic backgrounds. In all cases, transgenic placentae were significantly lighter throughout gestation, which was entirely due to a reduction in the spongiotrophoblast layer. There was also a reduction in glycogen staining and a progressive mislocalisation of cells from the spongiotrophoblast layer. These phenotypes were essentially restored by restored by normalising Phlda2 gene dosage in a single copy line. In addition, transgenic embryos were significantly lighter than wild type littermates from E16.5 onwards and were born 13% lighter. These embryos were asymmetrically growth restricted and displayed rapid post-natal catch up growth within two weeks of birth. Adult transgenic females that had undergone embryonic growth restriction also displayed increased adiposity and reduced glucose tolerance at one year of age. These data suggest that altered expression of Phlda2 and possibly Slc22a18 drive IUGR and program adult disease susceptibility. Recent human studies have found an association between elevated placental PHLDA2 and low birth weight or IUGR infants. This mouse model may thus provide a genetic tool that recapitulates a known human condition for further investigation of the fetal programming of metabolic syndrome.

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18

Delpisheh, Ali. "Maternal metabolic gene polymorphisms, pregnancy smoking and intrauterine fetal growth restriction." Thesis, University of Liverpool, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.428242.

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19

Alsafar, Ahmed Monadhil, and Ahmed Monadhil Alsafar. "Altered Adrenal Medulla Function in Fetal Sheep with Intrauterine Growth Restriction." Thesis, The University of Arizona, 2017. http://hdl.handle.net/10150/624903.

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Intrauterine growth restriction is a development condition commonly associated with insufficient placental delivery of nutrient and oxygen to the fetus. Among the important adaptations by the fetus are elevated blood catecholamine concentrations. In the current study, we examined two potential pathways which may mediate the observed epinephrine and norepinephrine concentrations in the adrenal medulla. The first of which is the catecholamine synthesis pathway consisting of four enzymes: TH, DDC, DBH and PNMT. Contrary to our prediction, mRNA expression of all four enzymes decreased compared to the controls (p<0.05 for DDC and PNMT). Second, we predicted the α2 adrenergic receptors to be downregulated in response to chronic catecholamine exposure. Our results showed a statistically significant decrease in mRNA concentrations of the ADRα2C isoform of the receptor, supporting our hypothesis that chromaffin cells were desensitized to inhibitory adrenergic receptors. Although more studies are needed to fully characterize the mechanisms, we conclude that catecholamine production and autocrine inhibitory activity was impaired in adrenal chromaffin cells.

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20

Diaz, Sílvia de Oliveira. "Pregnancy and newborns disorders followed by urine metabolomics." Doctoral thesis, Universidade de Aveiro, 2014. http://hdl.handle.net/10773/13110.

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Doutoramento em Química
Chapter 1 introduces the scope of the work by identifying the clinically relevant prenatal disorders and presently available diagnostic methods. The methodology followed in this work is presented, along with a brief account of the principles of the analytical and statistical tools employed. A thorough description of the state of the art of metabolomics in prenatal research concludes the chapter, highlighting the merit of this novel strategy to identify robust disease biomarkers. The scarce use of maternal and newborn urine in previous reports enlightens the relevance of this work. Chapter 2 presents a description of all the experimental details involved in the work performed, comprising sampling, sample collection and preparation issues, data acquisition protocols and data analysis procedures. The proton Nuclear Magnetic Resonance (NMR) characterization of maternal urine composition in healthy pregnancies is presented in Chapter 3. The urinary metabolic profile characteristic of each pregnancy trimester was defined and a 21-metabolite signature found descriptive of the metabolic adaptations occurring throughout pregnancy. 8 metabolites were found, for the first time to our knowledge, to vary in connection to pregnancy, while known metabolic effects were confirmed. This chapter includes a study of the effects of non-fasting (used in this work) as a possible confounder. Chapter 4 describes the metabolomic study of 2nd trimester maternal urine for the diagnosis of fetal disorders and prediction of later-developing complications. This was achieved by applying a novel variable selection method developed in the context of this work. It was found that fetal malformations (FM) (and, specifically those of the central nervous system, CNS) and chromosomal disorders (CD) (and, specifically, trisomy 21, T21) are accompanied by changes in energy, amino acids, lipids and nucleotides metabolic pathways, with CD causing a further deregulation in sugars metabolism, urea cycle and/or creatinine biosynthesis. Multivariate analysis models´ validation revealed classification rates (CR) of 84% for FM (87%, CNS) and 85% for CD (94%, T21). For later-diagnosed preterm delivery (PTD), preeclampsia (PE) and intrauterine growth restriction (IUGR), it is found that urinary NMR profiles have early predictive value, with CRs ranging from 84% for PTD (11-20 gestational weeks, g.w., prior to diagnosis), 94% for PE (18-24 g.w. pre-diagnosis) and 94% for IUGR (2-22 g.w. pre-diagnosis). This chapter includes results obtained for an ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) study of pre-PTD samples and correlation with NMR data. One possible marker was detected, although its identification was not possible. Chapter 5 relates to the NMR metabolomic study of gestational diabetes mellitus (GDM), establishing a potentially predictive urinary metabolic profile for GDM, 2-21 g.w. prior to diagnosis (CR 83%). Furthermore, the NMR spectrum was shown to carry information on individual phenotypes, able to predict future insulin treatment requirement (CR 94%). Chapter 6 describes results that demonstrate the impact of delivery mode (CR 88%) and gender (CR 76%) on newborn urinary profile. It was also found that newborn prematurity, respiratory depression, large for gestational age growth and malformations induce relevant metabolic perturbations (CR 82-92%), as well as maternal conditions, namely GDM (CR 82%) and maternal psychiatric disorders (CR 91%). Finally, the main conclusions of this thesis are presented in Chapter 7, highlighting the value of maternal or newborn urine metabolomics for pregnancy monitoring and disease prediction, towards the development of new early and non-invasive diagnostic methods.
O Capítulo 1 descreve o enquadramento deste trabalho identificando as doenças pré-natais relevantes e os métodos de diagnóstico actualmente disponíveis. É depois apresentada a metodologia seguida, assim como uma breve introdução dos princípios dos métodos analíticos e estatísticos aplicados. O capítulo é concluído com uma descrição do estado da arte na área de metabolómica em investigação pré-natal, identificando o mérito desta inovadora estratégia para a identificação de marcadores robustos de doenças pré-natais. A relevância deste trabalho torna-se clara através do escasso uso de urina materna e do recém-nascido em trabalhos anteriores. O Capítulo 2 descreve os procedimentos experimentais utilizados neste trabalho, incluindo condições de amostragem, recolha e preparação das amostras, protocolos de aquisição e de tratamento dos dados. A caracterização da composição da urina materna, através de espectroscopia de Ressonância Magnética Nuclear (RMN) de protão é apresentada no Capítulo 3. Define-se o perfil metabólico urinário característico para cada trimestre de gravidez, tendo sido encontrado um conjunto de 21 metabolitos descritivo das alterações metabólicas ocorridas ao longo da gravidez. 8 metabolitos foram encontrados a variar com a gravidez, pela primeira vez, tendo sido confirmadas variações metabólicas conhecidas. É ainda estudado o efeito do não-jejum (usado neste trabalho) como possível factor de confusão. O Capítulo 4 apresenta o estudo metabolómico de urina materna do 2º trimestre para o diagnóstico de doenças fetais e previsão de complicações mais tarde desenvolvidas. Este estudo compreende a aplicação de um método de selecção de variáveis desenvolvido no âmbito desta tese. Observou-se que as malformações fetais (e, especificamente, do sistema nervoso central, SNC) e as cromossomopatias (e, especificamente, a trissomia 21, T21) são acompanhadas por alterações nos metabolismos energético, dos aminoácidos, lípidos e nucleótidos, enquanto que as cromossomopatias mostraram ser acompanhadas por uma desregulação adicional dos metabolismos dos açúcares, ciclo da ureia e/ou biossíntese da creatinina. A validação dos modelos multivariados revelou taxas de classificação (CR) de 84% para malformações (87%, SNC) e 85% para CD (94%, T21). Para o parto pré-termo, pré-eclampsia (PE) e restrição de crescimento intrauterino (RCIU) observaram-se perfis que podem ajudar à previsão precoce, com CR 84% para pretermo (11-20 semanas de gestação, g.w. pré-diagnóstico), 94% para PE (18-24 g.w. pré-diagnóstico) e 94% para RCIU (2-22 g.w. pré-diagnóstico). Este capítulo inclui resultados obtidos por cromatografia líquida de ultra eficiência acoplada a espectrometria de massa (UPLC-MS) para pré-pretermo e correlação com os dados de RMN. Um possível composto marcador foi detectado mas a sua identificação não foi possível. O Capítulo 5 descreve o estudo metabolómico por RMN da diabetes mellitus gestacional (DMG), estabelecendo-se um perfil metabólico potencialmente preditivo da doença (CR 83%, 2-21 g.w. pré-diagnóstico). Verificou-se ainda que o espectro de RMN contém informação sobre o fenótipo individual, capaz de prever a necessidade futura de tratamento com insulina (CR 94%). No Capítulo 6 demonstra-se o impacto do tipo de parto (CR 88%) e género do bebé (CR 76%) no perfil da urina do recém-nascido. Verificou-se ainda que a prematuridade, depressão respiratória, crescimento grande para a idade gestacional e malformações induzem perturbações metabólicas relevantes (CR 82-92%), assim como algumas doenças maternas como a DMG (CR 82%) e doenças psiquiátricas (91% CR). Finalmente, no Capítulo 7 apresentam-se as principais conclusões deste trabalho, enfatizando o potencial da metabolómica de urina materna e do bebé para o acompanhamento da gravidez e previsão de doenças, visando o desenvolvimento de novos métodos de diagnóstico precoce e não-invasivo.

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21

Louey, Samantha 1977. "The effects of intrauterine growth restriction on postnatal growth, arterial pressure and the vasculature." Monash University, Dept. of Physiology, 2003. http://arrow.monash.edu.au/hdl/1959.1/7939.

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22

Abd-Rabou, Ayat. "Molecular genetic studies in pregnancies affected by preeclampsia and intrauterine growth restriction." Thesis, University of Nottingham, 2011. http://eprints.nottingham.ac.uk/14517/.

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Preeclampsia and fetal growth restriction (FGR) are common and costly obstetric complications. Both conditions are associated with immediate and remote mortality and morbidity for the mother and the offspring. Impaired placentation and aberrant maternal systemic responses are implicated as pathophysiological mechanisms in preeclampsia and FGR. Both preeclampsia and FGR are known to have a clear genetic basis. This study has investigated the roles of several candidate genes including those previously associated with diabetes (TCF7L2, FTO, PPAR-g, CDKN2B-AS1 and KCNJ11), and epidermal growth factor (EGF). Functional consequences of variants within the EGF gene were also investigated. A bidirectional association between type 2 diabetes (T2D) and preeclampsia is consistently reported, whereby each condition is associated with an increased risk of the other. Furthermore, fetal growth restriction, which complicates 30% of preeclamptic pregnancies, predisposes the offspring to an increased risk of type 2 diabetes and coronary artery disease (CAD) later in life. 11 single nucleotide polymorphisms (SNPs) reproducibly associated with T2D in the TCF7L2, FTO, PPAR-y, CDKN2B-AS1 and KCNJ11 genes were investigated as susceptibility loci for preeclampsia and fetal growth restriction in a maternal case control study. The study group consisted of 448 white western European women with preeclampsia, 673 controls with no evidence of preeclampsia, 243 women with pregnancies complicated by FGR, and 570 controls with no evidence of growth restriction. A maternal haplotype on the T2D region of the CDKN2BAS1 gene on chromosome 9p21 was found to be a risk variant for fetal growth restriction (P=O.005).The other 9 investigated SNPs in TCF7L2, FTO, PPAR-y, and KCNJ11 showed no association with growth restricted pregnancies. None of the SNPs investigated showed an association with preeclampsia. These findings suggest that some maternal diabetogenic risk variants are associated with an altered risk of FGR pregnancy but not preeclampsia. The results require replication in a larger sample and fetal-maternal gene interactions merit investigation. Epidermal growth factor (EGF) is described as a major regulator of the placentation process. It also helps to maintain an adequate blood supply to the growing fetus through its effects on umbilical vessel tone. Investigating the role of two genetic variants of the EGF gene in susceptibility to preeclampsia and FGR showed that the maternal variants, rs4444903 in the 5'UTR and rs2237051 in exon 14 of the EGF gene has no effect on the risk of preeclampsia or FGR pregnancy. The G allele of the SNP rs4444903 was associated with higher systolic blood pressure measures in the control group. The G allele of the rs4444903 and the A allele of rs2237051 have been associated with increased risk for FGR and lower birth weight in a previous study from our laboratory. This led to investigations to characterize the functional consequences of the two SNPs in the EGF gene on transcription, translation and ribonucleic acid (RNA) splicing using a variety of methods. These experiments have shown that the G allele of rs4444903 was transcriptionally more active than the A allele in hepatocellular carcinoma (HepG2) and more active than EGFP on its own in choriocarcinoma (Jeg-3) cell lines using a luciferase reporter gene assay. There was no effect of this variant on translational efficiency in the cell lines investigated using reporter gene assays, or in a cell free environment using an in vitro translation assay. DNA-protein interaction was investigated using nuclear extract from HepG2 cells to further define the mechanism by which the G allele exerts its higher transcriptional activity. Initial experiments suggest that the Sp1 transcription factor interacts with and represses the A allele of the rs4444903 SNP. The study also demonstrated no evidence of higher activity of the G allele on EGF expression in vivo using term placental tissues. It was expected that higher EGF expression as a function of genotype at rs4444903 SNP may lead to down regulation of the EGFR in the placenta, which was not confirmed in this study. SNP rs2237051 in exon 14 of the EGF gene is in strong linkage disequilibrium with rs4444903, and disrupts a predicted exon splicing enhancer region. This polymorphism was investigated using a minigene assay, but there was no evidence that it affected splicing of exon 14. Taken together, these findings provide no evidence that EGF genetic variants alter the risk of preeclampsia or FGR though functioning.

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Pla, Codina Laura. "Diagnosis and perinatal therapies in an animal model of intrauterine growth restriction." Doctoral thesis, Universitat de Barcelona, 2021. http://hdl.handle.net/10803/673611.

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This Ph.D. Thesis is structured on two projects aiming to improve the intrauterine growth restriction (IUGR) perinatal survival and brain development with new more accurate tools for continuous fetal monitoring and new prenatal therapies. The first project aims to test new implantable miniaturized pH and oxygen electrochemical sensors to be applicable in IUGR fetus. For this purpose, different animal models and species have been used. Data obtained from this project resulted in four articles published in international peer-reviewed journals. The second project aims to describe the structural brain and placental changes underlying IUGR and select and test potential effective strategies acting upon these specific targets in order to overcome IUGR effects and placental changes. This project have resulted in two articles, one of them has been published and the other one has been submitted, both in an international peer- reviewed journals. The articles of each project are the following: PROJECT 1: 1. Micro-needle implantable electrochemical oxygen sensor: ex-vivo and in-vivo studies 2020, Biosensors and Bioelectronics 2. In vivo Monitoring with micro-implantable hypoxia sensor based on tissue acidosis 2020, Talanta 3. Non-invasive monitoring of pH and oxygen using miniaturized electrochemical sensors in an animal model of acute hypoxia 2021, Journal of Translational Medicine 4. Miniaturized electrochemical sensors to monitor fetal hypoxia and acidosis in a pregnant sheep model 2021, Biomedicines PROJECT 2: 5. Structural Brain Changes during the Neonatal Period in a Rabbit Model of Intrauterine Growth Restriction 2021, Developmental neuroscience 6. Docosahexaenoic acid and lactoferrin effects on the brain and placenta in a rabbit model of intrauterine growth restriction 2021, Developmental neuroscience. Submitted. The presentation of the Thesis is structured with a general introduction followed by the hypothesis and objectives. After that, the articles that take part of each project are inserted entirely. Following the articles, it will be a brief summary of the global results and subsequently a general discussion and conclusions will be exposed.

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Kelly, Amy, and Amy Kelly. "Adaptations in the Pancreatic Islet Transcriptome of Intrauterine Growth Restricted Fetuses." Diss., The University of Arizona, 2017. http://hdl.handle.net/10150/624586.

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We established that acute adrenergic receptor stimulation in β-cells suppresses oxidative metabolism. This effect provides the basis for understanding how CAs reduce cell proliferation. Furthermore, the effects of acute CA on Min6 cells were distinguished from chronic CA culture using proteomics. Together, the RNAseq, qPCR and proteomic studies support a role for adrenergic receptor signaling in the regulation of proliferaton in β-cells. This work describes the genetic and proteomic profile underlying chronic adrenergic signaling and identifies CA independent suppression of β-cell growth and metabolism. Through the use of multiple models and comparative bioinformatics, we refined the list of molecular dysfunctions associated with the IUGR pathology to a set of specific and testable adrenergic targets.

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Chakraborty, Supratik. "The effect of intra uterine growth restriction (IUGR) on heart rate and blood pressure in children." Thesis, University of Leicester, 2011. http://hdl.handle.net/2381/9163.

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Infants with Intra Uterine Growth Restriction (IUGR) are reported to be more prone to develop obesity and cardiovascular problems as adults. Research in this field is complicated due to use of different statistical models and inadequate cardiovascular measurements. I intended to find out whether the difference in body size between IUGR and normal infants persisted through the childhood and whether there were any differences in cardiovascular parameters and maturation of circadian biorhythms between these groups. 75 nine year olds were recruited and forty-one of them were IUGR. All the children had their twenty-four hour heart rate variability, blood pressure and urinary Cortisol excretion measured. IUGR children showed a greater increase in their weight between birth and nine years but the z scores for current weight, height and Body Mass Index (BMI) and incidence of obesity were higher in the control group. Both groups showed similar diurnal variation of all cardiovascular parameters and no evidence of the cardiovascular system being dominated by the Sympathetic nervous system in the IUGR children, which could have been detrimental to their cardiovascular health. The Systolic Blood Pressure (SBP) was significantly higher in the control group. Later weight was the better predictor of SBP. BMI was a significant predictor of SBP. Urinary cortisol/Creatinine ratio was not different between the two groups. I conclude that IUGR children grow faster but remain shorter and lighter than their normal counterparts. IUGR children on average are physiologically indistinguishable from normal children and do not show any abnormality in the cardiovascular parameters, which could link them to future disease. Normal children have higher SBP than the IUGR children which is related to larger body mass. The current body size appears to have more impact on the level of blood pressure at the age of nine years compared to IUGR.

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Landis, Sarah Henry Meshnick Steven R. "A longitudinal ultrasound study of fetal growth and intrauterine growth restriction in Kinshasa, Democratic Republic of Congo." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2007. http://dc.lib.unc.edu/u?/etd,1245.

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Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2007.
Title from electronic title page (viewed Mar. 26, 2008). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Epidemiology." Discipline: Epidemiology; Department/School: Public Health.

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Haghighi, Poodeh S. (Saeid). "Novel pathomechanisms of intrauterine growth restriction in fetal alcohol syndrome in a mouse model." Doctoral thesis, Oulun yliopisto, 2016. http://urn.fi/urn:isbn:9789526213163.

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Abstract Fetal alcohol syndrome (FAS) is a pattern of anomalies in affected children due to maternal alcohol administration at vulnerable stages of fetal development. Intrauterine growth restriction and facial malformation are the presenting phenotypes of FAS. In this investigation, novel pathomechanisms of intrauterine growth restriction and facial malformation were the primary aims. We found by a FAS mouse model that AceCS1 gene expression and polyamines are the immediate targets of fetal alcohol exposure. The AceCS1 product is a precursor for lipid synthesis and protein acetylation and possibly, for polycation acetylation. We cloned the Mus musculus nuclear-cytosolic AceCS1 gene, and showed that its expression is developmentally regulated with a dynamic localization in the cytosolic and nuclear compartment. The enzyme plays an essential role in de novo synthesis of acetyl Coenzyme A. Fetal alcohol administration targets nutrient supplying networks, which are localized at critical barriers. The main findings were reduced surface of the labyrinthine zone, destruction of gap junctions in the hemotrichorial placenta, reduced syncytiotrophoblastic cell layers and loosening of interaction between cell layers and embryo endothelial cells, reduced Reichert’s membrane thickness with discontinued Reichert’s trophoblast and loss of interaction by Reichert’s-parietal cells, reduction of capillary network and reduced vascularization in the brain area, and perturbed neural crest migration and formation of neural tube defect. Alteration of angiogenesis -regulating proteins such as VEGF, PlGF, PECAM was detected in FAS, with no significant changes in placental angiogenesis of the labyrinthine zone, but up-regulation of VEGF/PlGF caused permeability changes in the placenta and yolk sac. On the other hand, the PECAM pool in embryos’ brain was reduced, which in turn led to decreased angiogenesis and vascularization
Tiivistelmä Sikiön alkoholisyndrooma (engl. Fetal alcohol syndrome, FAS) on joukko muutoksia, joita esiintyy äidin raskaudenaikaisen alkoholin käytön seurauksena, kun käyttö osuu sikiökehityksen kannalta kriittiseen vaiheeseen. Kohdunsisäisen kasvun rajoittuminen ja kasvojen epämuodostumat ovat FAS:n tyypillisimpiä ilmentymiä. Tässä tutkimuksessa pyrittiin löytämään uusia patomekanismeja kohdunsisäisen kasvun rajoittumiselle ja kasvojen epämuodostumille. Hiiren FAS-mallin avulla selvisi, että sikiön altistuminen alkoholille vaikuttaa suoraan AceCS1-geenin ilmentymiseen ja polyamiinien pitoisuuteen. AceCS1-geenin tuote on esiaste lipidien synteesissä ja proteiinien asetylaatiossa sekä mahdollisesti myös polykationien asetylaatiossa. Työssä myös kloonattiin hiiren (Mus musculus) AceCS1-geeni, jonka tuotetta esiintyy sekä tumassa että solulimassa. Lisäksi osoitettiin, että geenin ekspressio oli kehityksen aikana säädelty tuottamaan entsyymiä dynaamisesti eri paikkoihin solussa. Entsyymillä on lisäksi merkittävä osuus asetyyli-koentsyymi-A:n de novo–synteesissä. Sikiön altistuminen alkoholille kohdistuu sellaisten ravintoaineiden saatavuuteen, jotka sijaitsevat kriittisesti tärkeissä kudosrajapinnoissa. Päälöydöksinä olivat vähentynyt labyrinttikudoksen pinta-ala, gap-liitosten tuhoutuminen istukan veriesteessä (hemotrichorial?), ohentunut trofoblastisolujen kerros ja Reichertin kalvon paksuus, harventunut hiusverisuonten verkosto sekä verisuonitus aivojen alueella sekä hermopienan solujen siirtymishäiriö ja hermostoputken sulkeutumishäiriö. Verisuonten muodostumista (angiogeneesiä) säätelevien proteiinien (kuten VEGF, PlGF, PECAM) muutoksia todettiin FAS:ssa, mutta merkittäviä muutoksia ei havaittu istukan verisuonten muodostumisessa. VEGF/PlGF-suhteen suureneminen muutti istukan ja ruskuaispussin verisuonten läpäisevyyttä. Toisaalta sikiöiden aivojen PECAM-määrä pieneni, mikä johti verisuonten ja verisuoniverkoston muodostumisen vähenemiseen

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28

Ashworth, Janet R. "The role of the vascular endothelium in pregnancy, pre-eclampsia and intrauterine growth restriction." Thesis, University of Nottingham, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.401750.

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Morton, Jodi Mirissa. "Effects of intrauterine growth restriction on Wharton’s jelly cells and preweaning traits in pigs." Diss., Kansas State University, 2018. http://hdl.handle.net/2097/38757.

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Doctor of Philosophy
Department of Animal Sciences and Industry
Duane L. Davis
Intrauterine growth restriction (IUGR) affects all mammals. In the swine industry IUGR pigs result from intrauterine crowding. Prenatal programming in IUGR pigs has substantial effects on myogenesis and adipogenesis. Prenatal programming due to IUGR is also a problem in humans and long-term effects on adipogenesis are well established for small for gestational age (SGA) babies. Mesenchymal stem cells (MSCs) are the precursors for adipocytes. The umbilical cord contains a population of MSCs in Wharton’s jelly (WJ) and they can be harvested postnatally without ethical issues. Therefore, WJMSCs are proposed as models for studying prenatal programming of adipogenesis. We selected genes from studies of adipogenesis in humans and other species and examined their expression in pig WJ. We assigned pigs within litter as High, Medium, or Low birth weight and evaluated these categories for expression of Cox1, Cox2, EGR1, PPARɣ1, PPARɣ2, and Pref1. Differences due to size classification within litter were limited but there were correlations between weaning weight and delta cycle threshold (ΔCt) for EGR1 (r = 0.28; P < 0.009), PPARɣ1 (r = 0.29; P < 0.007), and PPARɣ2 (r = 0.30; P < 0.005). This may be consistent with the reports for SGA babies where EGR1 is upregulated by prenatal growth restriction. To gain insight into when during pregnancy IUGR affects WJ cells we collected umbilical cords at d 60 and d 95. In d 60 umbilical cords, small fetuses had increased (P = 0.06) Cox1 gene expression. We tested the ability of d 60 WJ cells to undergo adipogenic differentiation using standard protocols and a cycling protocol that exposed the cells to adipogenic differentiation conditions interposed with a rest phase with high insulin. It has been reported that the cycling protocol revealed increased glucose uptake in WJ cells from human SGA babies. We found that d 60 WJ cells did not show adipogenic differentiation in any of the protocols tested however glucose uptake correlated negatively with birth weight at Cycle 0 (P < 0.02; r = 0.61). In summary, pig WJ cells reveal some effects of IUGR but they appear to differ from the relationship demonstrated reported for human SGA babies. A new finding was that at midgestation pig WJ cells do not appear to be competent to complete adipogenesis. We also studied nursing managements to improve outcomes for IUGR pigs. Colostrum intake may be a problem, particularly for light weight pigs and those born later during farrowing. Split suckling is the removal of some pigs to allow others unrestricted nursing access. We temporarily removed the six heaviest pigs and this treatment increased gain and weight by d 7 of age. Colostrum intake was highest for the high birth weight pigs. When we temporarily removed the first half of the litter, colostrum intake was increased for the second half of litter born and the difference in immunocrit was reduced between the two litter halves.

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Moukayed, Meis. "HNF1[alpha] may be a molecular link in intrauterine growth restriction induced type 2 diabetes." Thesis, University of Cambridge, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620543.

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31

Wilson, Samantha Lea. "Genetic and epigenetic profiling of placental insufficiency : identifying biomarkers of preeclampsia and intrauterine growth restriction." Thesis, University of British Columbia, 2017. http://hdl.handle.net/2429/63939.

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32

Smith, Rachel Marie, and Rachel Marie Smith. "Impaired Satellite Cell Differentiation Capacity and Myotube Insulin Responsiveness in Lambs with Intrauterine Growth Restriction." Thesis, The University of Arizona, 2016. http://hdl.handle.net/10150/621571.

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Establishing adequate muscle mass is essential for metabolic health. Fetuses with intrauterine growth restriction (IUGR) are born with less muscle mass than appropriate for gestational age infants and never fully recover, as those born IUGR demonstrate persistent reductions in lean body mass in adulthood. Consequently, children and adults with IUGR have an increased risk of developing type 2 diabetes, obesity, and other complications associated with the metabolic syndrome. In order to better understand the in utero programming paradigm of IUGR on skeletal muscle growth and metabolism, we isolated satellite cells from one-month-old lambs and examined their function because of their role in muscle growth. In this series of experiments, we establish a differentiation protocol and show that satellite cells grown on Matrigel (P ≤ 0.05) and in the presence of a TGFβ inhibitor (P ≤ 0.05) have increased fusion events after 3 - 4 days of differentiation. Importantly we found that differentiation of IUGR satellite cells, measured by percent fusion, was greater than controls (P ≤ 0.05). However this difference was lost when cultures were exposed to a TGFβ inhibitor for 24 hours (P > 0.05). Using our optimized differentiation protocol to produce myotubes, we measured insulin-stimulated glucose uptake. IUGR myotubes were less responsive to insulin compared to controls (P < 0.01). These findings demonstrate for the first time that satellite cells from IUGR lambs exhibit disturbed glucose metabolism and differentiation capacity, which indicates that satellite cells become programmed by conditions associated with IUGR.

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González, Tendero Anna. "Multiscale characterization of cardiac remodeling induced by intrauterine growth restriction, at organ, cellular and subcellular level." Doctoral thesis, Universitat de Barcelona, 2014. http://hdl.handle.net/10803/283350.

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INTRODUCTION: Intrauterine growth restriction (IUGR) due to placental insufficiency affects up to 7-10% of pregnancies and is a major cause of perinatal mortality and long term morbidity. IUGR results in low birth weight, which is associated with increased risk of cardiovascular mortality in adulthood, and is thought to be mediated by fetal cardiovascular programming. IUGR fetuses show signs of cardiac systolic and diastolic dysfunction from early stages, together with the appearance of biochemical signs of cell damage, changes in cardiac morphometry and function. These fetal changes persist permanently, resulting in vascular and cardiac remodelling. HYPOTHESIS: IUGR induces cardiac remodeling and dysfunction at organ, cellular and organelle level. OBJECTIVE: To characterize cardiac remodeling and function in IUGR, at organ, cellular and organelle level. METHODOLOGY: Cardiac remodeling due to IUGR has been evaluated in in two study groups: 1) human IUGR fetuses; 2) an experimental model of IUGR in New Zealand rabbit which has been previously validated. Several imaging techniques have been used to evaluate cardiac remodeling in IUGR: 1) X-ray synchrotron radiation to evaluate detailed cardiac anatomy; 2) transmission electron microscopy to study the intracellular organization of the cardiomyocyte; 3) multiphoton and second harmonic generation microscopy to evalaute the morphometry and ultrastructure of the sarcomere. Additionally, stuctural changes have been accompained with the evaluation of cardiac function with echocardiography and the evaluation of the gene expression profile. Cardiac remodeling has been evaluated in fetuses and the postnatal persistence of some of the changes has been assessed. RESULTS: At the organ level, fiber orientation is altered in IUGR fetal hearts and coronary vessels appear to be dilated. The intracellular organization of the cardiomyocyte of IUGR fetal hearts presents changes affecting the relationship between mitochondria and myofilaments. At the level of the sarcomere, which is the main contractile unit, sarcomere length results to be shorter in IUGR fetal hearts. The latest persists in postnatal life. Signs of cardiac remodeling of IUGR hearts are associated to a subclinical cardiac dysfunction and changes in the expression of groups of genes functionally related, involved in oxygen homeostasis, energy production and the M-band of the sarcomere. CONCLUSIONS: Signs of cardiac remodeling induced by IUGR are described in this Thesis, from the whole cardiac architecture, through the cardiomyocyte intracellular organization, to the ultrastructure of the sarcomere. Moreover, the structural changes are associated with cardiac dysfunction and gene expression alterations. Specifically, we demonstrate: 1) the detailed cardiac anatomy is different in IUGR fetal hearts, with changes in fiber orientation and coronary vessels dilation; 2) the arrangement of the intracellular organelles of the cardiomyoycte is altered in IUGR fetuses, affecting mitochondria and their interaction with myofilaments; 3) sarcomere length is shorter in IUGR fetuses, which could result in decreased contractility; 4) shorter sarcomere length persists in postnatal life, suggesting that IUGR-induced changes on sarcomere morphometry during fetal life could contribute to the increased risk of cardiovascular disease in adulthood; 5) the described changes of cardiac remodeling are associated with subclinical cardiac dysfunction in IUGR fetuses and changes in the expression of groups of genes involved in oxygen homeostasis, energy production and the sarcomere M¬band.
INTRODUCCIÓN: La restricción de crecimiento intrauterino (CIR) debido a insuficiencia placentaria afecta a un 7-10% de las gestaciones y constituye la mayor causa de mortalidad perinatal i morbilidad a largo plazo. El CIR resulta en bajo peso al nacer, lo que se relaciona con un incremento de la mortalidad por causas cardiovasculares en edad adulta, y se cree que está mediado por el concepto de “programación fetal” de la función cardiovascular. HIPÓTESIS: El CIR induce un remodelado cardiaco acompañado de disfunción cardiaca, a nivel del órgano, célula y orgánulo. OBJETIVOS: Caracterización del remodelado y función cardiaca en el CIR, a nivel de órgano, célula y orgánulo. METODOLOGÍA: Estudio del remodelado cardíaco en CIR en dos grupos de estudio: 1) fetos CIR humanos; 2) modelo animal de CIR previamente validado. Se han usado distintas técnicas avanzadas de imagen para estudiar el remodelado cardiaco en CIR: 1) micro-CT por rayos X generados por sincrotrón para el estudio de la arquitectura detallada del corazón; 2) microscopía electrónica de transmisión para la evaluación de la organización intracelular del cardiomiocito; 3) microscopia multifotón e imagen de segundo harmónico para el estudio de la morfometría del sarcómero. Se ha evaluado la función cardiaca mediante ecocardiografia y análisis bioinformático del perfil de expresión génica. RESULTADOS: A nivel de órgano, la orientación de las fibras se encuentra alterada en fetos CIR y los vasos coronarios dilatados. A nivel del cardiomicito, la organización intracelular presenta cambios afectando mayormente la relación entre mitocondrias y miofilamentos. La longitud del sarcómero, unidad contráctil fundamental, es inferior en corazones de fetos CIR. Esta última alteración persiste en vida postnatal. Los cambios estructurales de los corazones CIR se acompañan de signos de disfunción cardiaca subclínica y cambios en la expresión de grupos de genes funcionalmente relacionados, involucrados en la homeostasis del oxígeno, la producción de energía y la banda M del sarcómero. CONCLUSIONES: Los cambios descritos proporcionan evidencias de los mecanismos involucrados en el remodelado cardíaco asociado al CIR. Además, dichos cambios estructurales se asocian con una disfunción cardíaca y cambios a nivel de expresión génica.

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Levine, Hester Ann. "Maternal prenatal stress, fetoplacental hemodynamics, and early childhood development in the context of intrauterine growth restriction." Thesis, Queen's University Belfast, 2017. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.727420.

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Intrauterine growth restriction (IUGR) occurs in 5-8% of pregnancies and is associated with neonatal and paediatric morbidity and mortality. The aims of this follow-up study were to 1) determine whether pregnancy-specific stress (PSS) is associated with fetoplacental hemodynamics or neonatal outcomes in women with small for gestational age (SGA) pregnancies, and 2) examine differences in health-related quality of life (HRQoL), behavioural problems, and visual-motor integration (VMI)' in SGA three-year-olds. Measures used included the Prenatal Distress Questionnaire, the Pediatric Quality of Life Inventory, the Child Behavior Checklist, and the Beery-Buktenica Developmental Test of Visual-Motor Integration. PSS was associated with decreased UA PI and MCA PI, increased odds of AEDF, decreased CPR, birth weight <2500 g, prematurity, and decreased odds of NICU admission. IUGR children had poorer HRQoL, more affective and withdrawn behavioural problems, and poorer VMI than SGA children. Children who had been exposed to AEDF had more somatic complaints, withdrawn, attention, and internalising behavioural problems, and children who had been exposed to abnormal CPR had more withdrawn and attention behavioural problems. Term IUGR children had poorer physical functioning than preterm SGA children. Preterm IUGR children had more attention problems and poorer VMI than term SGA children, and more oppositional defiant, withdrawn, aggressive, and externalising behavioural problems than preterm SGA children. Male IUGR children had poorer HRQoL, more behavioural problems, and poorer VMI. This multicentre prospective observational study provided a unique opportunity to comprehensively assess PSS and early childhood development in a large cohort of women and SGA children in Ireland and Northern Ireland. This study provides the first available evidence of associations between PSS and fetoplacental hemodynamics and neonatal outcomes in SGA pregnancy. This study also provides novel insights into the developmental differences between SGA and IUGR children, and into the specific developmental vulnerabilities of premature or male IUGR children.

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Egbor, Michael Agbor. "Stereological investigation of placental villous and vascular morphology in pre-eclampsia with and without intrauterine growth restriction." Thesis, Brunel University, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.423332.

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36

Alexander, Kristen Lena. "Differential Receptors for Advanced Glycation End-Products (RAGE) Expression in Preeclampsia, Intrauterine Growth Restriction and Gestational Diabetes." BYU ScholarsArchive, 2015. https://scholarsarchive.byu.edu/etd/5463.

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Preeclampsia (PE), intrauterine growth restriction (IUGR) and gestational diabetes (GDM) increase the risk of maternal and fetal morbidity and mortality. The roles of Advanced Glycation End-products (AGEs) are already well documented concerning inflammation, hypoxia and oxidative stress. AGEs bind to its receptor, Receptor for Advanced Glycation End-products (RAGE), and activate an inflammatory pathway. This pathway alters the efficacy of invasive trophoblast cells and in the placenta and can result in placental dysfunction. We hypothesized that the placental dysfunction found in PE, IUGR, and GDM resulted from an over activation of the RAGE-mediated inflammatory pathway. Using human placental samples, we found that RAGE protein expression via western blotting was increased in PE and decreased in IUGR while GDM remained similar to that of control placentas. We then wanted to determine the efficacy of RAGE activation to alter the invasive nature of invasive cytotrophoblasts cells. We found that the addition of AGEs to SW71 cells decreases invasion through the activation of JNK and ERK cellular signaling pathways. Altogether these findings suggest that RAGE activation in trophoblast cells seems result in insufficient placental pathogenesis causing PE, however the IUGR and GDM samples we obtained did not seem to have resulted from RAGE activation. We also found that RAGE activation can alter the ability of invasive trophoblasts to invade, thus limiting the ability of the placental cells to remodel the maternal spiral arteries. We believe that further research into specific triggers of IUGR (smoking-induced) and un-treated diabetes could result in RAGE stimulated placental insufficiency.

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Sipos, Peter. "The role of endothelial progenitor cells in the utero-placental vasculature." Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/the-role-of-endothelial-progenitor-cells-in-the-uteroplacental-vasculature(b808fc6d-e55a-4e8d-82da-dd7a4c9a1df0).html.

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Fetal growth in utero depends on nutrient and oxygen reaching the fetus through the uterine and placental microcirculations, both undergoing massive expansion during pregnancy. Aberrations of the placental vasculature are associated with Intrauterine Growth Restriction (IUGR), a common pathological outcome of pregnancy; however, the cellular components responsible for vessel formation in the placenta and the uterus remain unknown. Endothelial Progenitor Cells (EPC) are a group of morphologically and functionally varied bone marrow derived vasculogenic cell types, divided into two major subsets: (i) Circulating Angiogenic Cells (CACs), which promote vessel formation by interfering with the extracellular matrix and (ii) Endothelial Colony Forming Cells (ECFCs), which provide the source for new endothelium. This role has been demonstrated in pathophysiological studies, but not in normal physiological events in vivo. Fetal ECFCs are more proficient than their adult counterparts, but it is unclear in what specific fetal or maternal physiological situations fetal ECFCs are involved. Based upon these considerations, it was hypothesised that: (i) fetal-derived ECFCs play a role in placental vasculogenesis, (ii) these cells transmigrate the placenta and home to loci of vessel formation in the pregnant uterus, and that (iii) intrinsic alterations in their capabilities are associated with fetal growth restriction during intrauterine life. To support these hypotheses the following experiments were performed;(i) EPCs in blood from pairs of human umbilical arteries and veins were counted by flow cytometry. Numbers of EPCs in these samples showed an arterio-venous gradient suggesting their placental sequestration. Furthermore, ECFCs were isolated from human umbilical blood using established culture techniques. Labelled human fetal ECFCs were transplanted into the circulation of murine fetuses using an ultrasound-guided intra-cardiac injection. Using a fluorescent imager and microscopy these cells were shown to home to the murine placenta and participate in vasculogenesis.(ii) Male mice ubiquitously expressing eGFP were crossbred with native females, and fetal (eGFP-positive) endothelial-like cells integrated into the uterine microvasculature. Human fetal ECFCs injected into murine fetuses were shown to migrate to the maternal uterus and became functionally involved with the microvasculature. In humans, microvessels were isolated from uterine biopsies of mothers with male offspring. Copies of the male specific SRY gene (quantified by RT-QPCR) indicated that cells of fetal origin constituted 12% of the endothelium in these vessels. In cross-sections, hybridisation of the Y-chromosome demonstrated the presence of fetal cells in the maternal endothelium of the human uterus. (iii) Using flow cytometry, fewer EPCs were defined within the peripheral circulation of growth-restricted babies. Functional assays showed that ECFCs derived from these growth-restricted cases had intrinsically impaired proliferation, migration, matrix-metalloproteinase (MMP-2) production, and generated fewer blood vessels in a murine vasculogenic bioassay. These results demonstrated the vasculogenic capacity of human fetal ECFCs in vivo and established them as key players in human placental vasculogenesis and uterine vessel expansion. Notably, these results also showed a link between impaired function of fetal ECFCs and IUGR, which is associated with increased cardiovascular risk of both the fetus as an adult, and mother in later life. From these findings it could be speculated, that intrinsic changes in ECFC-biology may be the causative link between IUGR and fetal and maternal cardiovascular susceptibility. Insight into these processes may contribute to early diagnosis, prevention and treatment of IUGR and associated conditions.

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Jain, Arjun. "Role of ET-1 in the induction of placental endoplasmic reticulum stress in pre-eclampsia and intrauterine growth restriction." Thesis, University of Cambridge, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.610243.

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Cruz, Lemini Mónica Cristina. "Fetal cardiovascular dysfunction in intrauterine growth restriction as a predictive marker of perinatal outcome and cardiovascular disease in childhood." Doctoral thesis, Universitat de Barcelona, 2013. http://hdl.handle.net/10803/134221.

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Most risk factors leading to cardiovascular disease are already present in childhood and the importance of early identification of pediatric cardiovascular risk factors is now well recognized. Hypertension in the child has been associated with substantial long-term health risks and considered an indication for lifestyle modifications. Current clinical guidelines contemplate screening for hypertension in children over 3 years of age, in order to provide strategies for promoting cardiovascular health, which can be integrated into comprehensive pediatric care. Interventions in the IUGR group could go from blood pressure monitoring before 3 years of age, recommending lack of exposure to other risk factors (secondary smoking, obesity), surveillance of catch-up growth or administration of hypotensors and specially, promoting exercise and physical activity. A recent randomized trial in a large cohort of children suggest that the inverse association of fetal growth with arterial wall thickness in childhood can be prevented by dietary ω-3 fatty acid supplementation over the first 5 years of life. IUGR is not listed among those conditions presumed to increase cardiovascular risk, in current guidelines. Considering IUGR affects 5-10% of all newborns, the findings of this study would affect thousands of children per year. Currently, there are no prenatal parameters described that may aid in selecting those fetuses with later hypertension and arterial remodeling that may benefit for early screening in infancy and other preventive measures or interventions. Both fetal and child cardiovascular evaluations have proven to be reliable techniques for describing changes in IUGR; cardiovascular dysfunction has been found subclinically and may have implications for cardiovascular risk in future life. The main aim of this work was to evaluate cardiovascular function parameters in IUGR fetuses as predictors of perinatal and postnatal cardiovascular outcome. In order to do this, we looked to validate the reproducibility of measurements and techniques not previously described in IUGR fetuses (studies 1 and 2), to evaluate whether fetal cardiovascular parameters could help us predict perinatal outcome (study 3) and finally to assess the value of fetal echocardiography for prediction of postnatal cardiovascular risk factors, specifically hypertension and arterial remodeling (study 4). This thesis confirms previous studies showing fetal cardiac dysfunction can be documented by fetal echocardiography; it validates different methods for evaluating cardiac function in the fetus and demonstrates the predictive value of these parameters for perinatal and postnatal cardiovascular outcome. Our first study demonstrates for the first time the validity of M-mode to assess longitudinal axis motion in IUGR. It further confirms previous research that IUGR fetuses have a significant decrease in longitudinal myocardial motion, as part of the fetal cardiovascular adaptation to placental insufficiency. In our second study, both TDI and 2D-derived strain analysis demonstrated to be feasible and reproducible to evaluate deformation parameters in the fetal heart. Our third study evaluated the independent and combined contribution of fetal cardiovascular parameters to the prediction of early-onset IUGR perinatal mortality. The study suggests an algorithm illustrating the chances of perinatal death against gestational age and DV, which might help clinical decisions in the management of early-onset IUGR fetuses. The fourth study provides, for the first time, evidence that fetal echocardiographic parameters are strongly associated to postnatal hypertension and arterial remodeling, which are recognized cardiovascular risk factors and surrogates for early-onset cardiovascular disease. It supports that a fetal cardiovascular score is strongly associated with the presence of postnatal hypertension and arterial remodeling at 6 months of age in IUGR. Echocardiographic parameters demonstrated a far better performance than perinatal factors and fetoplacental Doppler used for establishing the severity of IUGR.
Los fetos con restricción del crecimiento intrauterino (RCIU) presentan remodelamiento cardiovascular el cual persiste en la infancia y se ha asociado a enfermedades cardiovasculares en el adulto. La hipertensión en la infancia se ha demostrado como un factor de riesgo cardiovascular para la enfermedad adulta. Un seguimiento estricto junto con intervenciones en la dieta se ha demostrado mejora la salud cardiovascular en estos niños, sin embargo no todas las restricciones del crecimiento tienen hipertensión en la infancia. El objetivo principal de esta tesis es definir los parámetros con mayor utilidad de la ecocardiografía fetal para predecir hipertensión y remodelamiento arterial en infantes de 6 meses de edad con restricción del crecimiento intrauterino. Para esto, se realizó un estudio de cohorte incluyendo fetos con RCIU y controles, seguidos desde vida prenatal hasta los 6 meses de edad. La evaluación prenatal consistió en una ecocardiografía funcional completa. A los 6 meses de edad estos niños fueron evaluados para hipertensión y remodelamiento arterial. Posteriormente se realizó la construcción de un score cardiovascular para determinar desde vida prenatal aquellos niños con mayor riesgo a presentar hipertensión en vida postnatal y que pudieran requerir vigilancia o intervenciones.

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Atkinson, Jessica. "An in-vivo structural MRI investigation of newborn infants' brains : preterm infants and infants born with intrauterine growth restriction." Thesis, University of Liverpool, 2012. http://livrepository.liverpool.ac.uk/2002304/.

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Introduction: It is well documented that preterm infants are less developed than term infants at term age and infants with IUGR are said to be of higher vulnerability. Fractional Anisotropy (FA) and Apparent Diffusion Coefficient (ADC) are sensitive to micro structural abnormalities and increases in anisotropy associated with premyelination are the earliest indications of the beginning processes of myelination. Furthermore reductions in brain volumes have been found in preterm infants compared to controls and IUGR infants. Thyroxine (T4) is necessary for normal growth and development of the central nervous system. Infants born preterm miss out on the maternal transfer of T4 that occurs during the third trimester and are born with an underdeveloped thyroid gland that is not yet producing sufficient amounts of T4. Method: Sixty nine infants (51 preterm, 9 IUGR and 9 controls) were imaged on a 1.5 Telsa MRI Scanner. DTI analysis was performed using medical imaging software (DTIstudio). FA and ADC maps were used to draw regions of interest around the posterior limb of the internal capsule (PLIC), corpus callosum (CC), frontal lobes (FL) and occipital lobes (OL). The software Brain Voyager QX (version 1.9.10) was used for image realignment and demarcation of T2 Weighted images and the images were analysed using medical imaging software for structure- specific brain volume measurements (Easymeasure). Statistical analysis was conducted with repeated measures ANOVA using SPSS version 18. Results: A significant interaction when investigating anterior vs. posterior structures and laterality of structures with treatment in the frontal lobes and posterior limb of the internal capsule was found suggesting a group difference between infants treated with levothyroxine and those receiving placebo. IUGR infants generally had lower FA and ADC than the control group. Generally lower structural volumes were found in the placebo and IUGR group. Conclusion: Administration of levothyroxine affects the structures on different sides of the brain differently and raises structural volumes. Levothyroxine may be of particular benefit to infants with low levels of thyroxine in their blood (hypothyroxinemia) and male preterm infants. Preterm infants born with intrauterine growth restriction are of higher vulnerability than appropriate for gestational age preterm infants with lower FA, higher ADC and lower structural volumes. Further research is required to fully explore asymmetries in the preterm and IUGR brain and should look at administering levothyroxine to infants with low levels of thyroxine in their blood.

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Hirschi, Budge Kelsey May. "RAGE and Gas6/Axl Signaling in Obstetric Complications." BYU ScholarsArchive, 2020. https://scholarsarchive.byu.edu/etd/8409.

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Current research spans a wide range of objectives whose diversity includes the understanding of global epidemiology and the detailing of molecular interactions leading to specific pathologies. This work aligns more closely with the goal of mechanistic clarity by elucidating several aspects of signaling pathways involved in inflammatory and obstetric pathologies. Prior research has confirmed the role of Receptors for Advanced Glycation End-Products (RAGE) activation in signaling leading to chronic inflammation such as that observed in chronic obstructive pulmonary disease (COPD). RAGE activation has also been identified in other disease states including diabetes, Alzheimer’s disease, osteoarthritis, and cancers. We examined the role of RAGE in the obstetric complication intrauterine growth restriction (IUGR) wherein fetal development is delayed and infants are born at low birthweight. Exposure to tobacco smoke is known to activate RAGE, and smoke exposure also increases risk for IUGR. We confirm a role for RAGE signaling in development of IUGR. RAGE inhibition by semi-synthetic glycosaminoglycan ethers (SAGEs) significantly improved fetal and placental weights and reduced inflammatory signaling molecules. Interactions between RAGE and other signaling pathways have been noted in several research endeavors, and we sought to further understand signaling interactions specifically in obstetric pathologies by examining relationships between RAGE and Gas6/AXL signaling. We confirm that RAGE and Gas6/AXL signaling are not independent. Using tobacco smoke as a means of inducing RAGE, we determined that total AXL is inhibited when RAGE is active, but that phosphorylated AXL is increased. Inhibition of RAGE also increased Gas6 expression. These interactions require further clarification, but provide a foundation to expand upon. We further studied interactions within the Gas6/AXL pathway independent of RAGE. High levels of Gas6 have been noted in the serum of some women with preeclampsia, and early diagnosis and treatment of preeclampsia are currently limited. We demonstrate that, in a rat model, administration of Gas6 during pregnancy is sufficient to induce symptoms of preeclampsia including high blood pressure, increased proteinuria, and decreased trophoblast invasion. This provides a novel model which will further both diagnosis and treatment of preeclampsia. We also demonstrated that trophoblast invasion is influenced in a cell-type dependent manner by Gas6 and mTOR signaling, with decreased trophoblast invasion when Gas6 is high in trophoblast cells, but increased invasion with high Gas6 in a pulmonary adenocarcinoma cell type and in oral squamous cell carcinoma cells. Our work has clarified details of both RAGE and Gas6/AXL signaling that are crucial to further study of the pathways in which they are active, and the pathologies resulting from signaling misregulation.

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Brito, Mariana Lopes de. "Crescimento somático nos seis primeiros meses de vida de lactentes expostos ao tabagismo materno durante a gestação." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2014. http://hdl.handle.net/10183/110311.

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Objetivo: Verificar os efeitos do tabagismo materno durante a gestação sobre o crescimento de lactentes nos seis primeiros meses de vida. Métodos: Estudo observacional longitudinal, utilizando amostra de conveniência de recém-nascidos (RN), divididos em três grupos: filhos de mães tabagistas, àqueles com restrição de crescimento intrauterino idiopático (RCIU) e um grupo controle. A amostra foi selecionada em dois hospitais de Porto Alegre, capital estadual situada no extremo sul do Brasil, no período de 2011 a 2014. Os recém-nascidos foram avaliados ao nascimento, aos 7 e 15 dias, no primeiro, terceiro e sexto mês. As medidas antropométricas utilizadas foram peso, comprimento, perímetro cefálico e dobras cutâneas. Os indicadores de crescimento utilizados foram expressos em escore-z (OMS). As análises foram realizadas pelo método de Equações de Estimativas Generalizadas. Resultados: A amostra foi composta por 194 duplas mãe/recém-nascidos: 71 no grupo tabaco, 23 no grupo RCIU e 100 no grupo controle. Em relação ao peso ao nascer, o grupo tabaco apresentou menor média em comparação ao controle (p=0,002) e o grupo RCIU diferiu de ambos (p<0,001). Comprimento ao nascer do grupo tabaco e controle foram semelhantes, porém o grupo RCIU foi menor que ambos (p<0,001). Não houve diferença na trajetória de crescimento entre o grupo tabaco e controle, porém foram verificadas diferenças no crescimento do grupo RCIU em relação aos demais. Conclusão: A restrição de crescimento intrauterino mostrou ter maior impacto sobre a trajetória de crescimento dos lactentes estudados, independente de outros fatores, como o fumo e a alimentação.
Objective: To investigate the effects of maternal smoking during pregnancy on the growth of infants in the first six months of life. Methods: Longitudinal observational study using a convenience sample of newborns (NBs) divided into three groups: infants of smoking mothers (tobacco), with idiopathic intrauterine growth restriction (IUGR), and a control group. The sample was selected from two hospitals in Porto Alegre, located in southern Brazil, between 2011 and 2014. NBs were evaluated at birth, 7 and 15 days, and in the first, third, and sixth month. Anthropometric measures were weight, length, head circumference, and skinfold thickness. The growth indicators used were expressed as z-scores (WHO). The analyses were performed using the generalized estimating equation method. Results: The sample included 194 mother/newborn pairs: 71 tobacco group, 23 IUGR group, and 100 control group. In terms of weight at birth, tobacco was lower than that of the control (p=0.002) and the IUGR had a statistically significant difference when compared with both the other groups (p<0.001). The birth length tobacco and control groups were similar, but the IUGR group was lower than both (p <0.001). We found no differences in growth trajectory between tobacco and control group, but there were differences in the growth of the IUGR group when compared with the other groups. Conclusion: Intrauterine growth restriction had major impact on the growth trajectory of the infants studied, regardless of other factors, such as smoking and diet.

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Batallé, Bolaño Dafnis. "Brain connectivity network models based on multi-modal MRI to study brain reorganization of prenatal origin using intrauterine growth restriction as a model." Doctoral thesis, Universitat de Barcelona, 2014. http://hdl.handle.net/10803/283283.

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This PhD thesis is focused in the application of brain network models obtained from different modalities of magnetic resonance imaging (MRI) to characterize anomalies in neurodevelopment of a prenatal origin, using intrauterine growth restriction (IUGR) as a clinical model. Importantly, IUGR due to placental insufficiency affects 5-10% of all pregnancies and is a leading cause of fetal morbidity and mortality. The thesis is presented as a compendium of four studies published in international journals. Each of the studies is focused in the characterization of IUGR using brain networks obtained from a specific MRI modality (structural, diffusion and functional MRI) in a specific pediatric stage in the life of subjects with IUGR (neonatal, early infancy and pre-adolescence age). The first study focuses in the characterization of brain reorganization produced by IUGR at one year of age using brain networks based on a tractography obtain from diffusion MRI, using diffusion tensor imaging (DTI) approach. In this study it is demonstrated that brain network features of IUGR infants have alterations associated with an altered neurodevelopment later in life. The second study assess the viability to use a novel methodology to obtain structural brain networks based on simple anatomical MRI based on the similitude of gray matter (GM) patterns among different areas of the brain. We demonstrated alterations in infants with IUGR using this technique, and that the alterations found are also associated with neurodevelopmental problems found later in life. In the third study we used a rabbit model of IUGR to explore if the alterations in the structural brain network persist at long-term, during preadolescence. We demonstrated that indeed, there are alterations in the structural brain network organization that persist at long-term and that this alterations are associated with neurobehavioral outcomes. Finally, using normalization approaches, we observed a peculiar compensatory effect in the subjects with IUGR. In the forth study, we assessed functional brain networks of neonates with IUGR, demonstrating that this condition produces a reorganization of functional brain connectivity since such an early age, characterized by a pattern of increased co-activation and synchronization of brain regions together with a suboptimal organization when assessing normalized networks. In addition, functional brain network features were also associated to neurobehavioral alterations. Overall, our main conclusion is that IUGR condition produces structural and functional brain reorganization since early life that persists postnatally up to pre-adolescence. We hypothesize that the observed functional and structural reorganization could be a potential substrate of high risk of altered neurodevelopment in infants with IUGR, and postulate this condition as a possible brain network disorder. Importantly, the association of network features with neurobehavior and neurodevelopment since an early age opens the opportunity to further develop early image biomarkers of altered neurodevelopment, a clinical chance to improve the management of a condition that affects up to 10% of deliveries.
Aquesta tesis doctoral està centrada en l'aplicació de models de xarxa del cervell obtinguts a partir de diferents modalitats de ressonància magnètica (RM) per caracteritzar anomalies en el desenvolupament d'origen prenatal utilitzant la restricció de creixement intrauterí (RCIU) com a model clínic. La tesi està presentada com a compendi de quatre estudis publicats en revistes internacionals de primer quartil. Cada un dels estudis està centrat en la caracterització de la RCIU mitjançant xarxes cerebrals obtingudes a partir d'una modalitat de RM determinada en una etapa pediàtrica diferent, en la vida de subjectes amb RCIU. Així doncs, el primer estudi es centra en la caracterització de la reorganització cerebral produïda per RCIU a l'any de vida mitjançant xarxes cerebrals estructurals basades en RM per difusió. En aquest estudi es demostra que les característiques de xarxa en els subjectes amb RCIU presenten una sèrie d'alteracions relacionades amb un neuro-desenvolupament futur anormal. El segon projecte analitza la utilització de xarxes estructurals cerebrals basades en RM anatòmica convencional per caracteritzar alteracions en nens d'un any amb RCIU. Es demostra que efectivament amb aquesta tècnica també es troben alteracions en els infants amb IUGR, i que aquestes alteracions estan també relacionades amb problemes en el neuro-desenvolupament posterior. En el tercer projecte s'utilitza un model animal de conill amb RCIU per explorar les alteracions en la xarxa cerebral estructural que persisteix a llarg termini. Es demostra que efectivament existeixen alteracions en la organització estructural del cervell persistents a llarg termini i s'observa un efecte compensatori en els subjectes amb RCIU. En el quart projecte s'analitzen les xarxes cerebrals funcional en neonats amb RCIU, demostrant que aquesta condició prenatal genera una reorganització en la connectivitat cerebral que té un substrat funcional, que es pot observar des d'etapes molt precoces de la vida i que està relacionada amb resultats de neuro-comportament.

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Cruz, Martínez Rogelio. "Cerebral and cardiac Doppler parameters in the identification of fetuses with late-onset intrauterine growth restriction at risk of adverse perinatal and neurobehavioral outcome." Doctoral thesis, Universitat de Barcelona, 2010. http://hdl.handle.net/10803/2506.

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Evaluation of fetal brain and cardiac Doppler parameters improves the identification of term, SGA fetuses with normal UA Doppler at risk of adverse perinatal outcome and abnormal neurobehavioral performance.

SPECIFIC HYPOTHESIS:

1. Cerebral blood perfusion is increased in SGA fetuses with normal umbilical artery Doppler as compared with normally grown fetuses.

2. Increased cerebral blood perfusion is earlier detected by means of the fractional moving blood volume using power Doppler ultrasound than by spectral Doppler indices.

3. Incorporation of fetal cardiac Doppler parameters might improve the identification of SGA fetuses with late-onset growth restriction.

4. Combination of power and spectral brain Doppler indices could improve the prediction of emergency cesarean section for intrapartum fetal distress after labor induction in term, SGA fetuses.

5. Abnormal cerebral blood perfusion discriminates SGA fetuses at risk of abnormal neurobehavioral performance with a better sensitivity than spectral Doppler indices.

To evaluate the contribution of fetal brain and cardiac Doppler parameters in identifying SGA fetuses with late-onset intrauterine growth restriction at risk of emergency cesarean section for intrapartum fetal distress and abnormal neonatal neurobehavioral performance.

SPECIFIC OBJECTIVES:

1. To establish normal reference intervals of fetal regional brain blood perfusion using power Doppler ultrasound as measured by FMBV.

2. To construct normal reference ranges of left modified myocardial performance index in near-term fetuses.

3. To compare the temporal sequence of fetal brain hemodynamic changes in near-term SGA fetuses, as measured by spectral-Doppler indices or by FMBV.

4. To evaluate the changes in myocardial performance index, aortic isthmus and ductus venosus in term, SGA fetuses with normal umbilical artery Doppler.
5. To explore whether a combination of brain Doppler parameters could improve the prediction of emergency cesarean section for fetal distress and neonatal acidosis after labor induction in term SGA fetuses.

6. To evaluate changes in cerebral blood perfusion and middle cerebral artery Doppler in term SGA fetuses and to explore their association with neonatal neurobehavioral performance.

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45

Kouskouti, Christina [Verfasser], and Franz [Akademischer Betreuer] Kainer. "Short term fetal heart rate variation in intrauterine growth restriction : development of reference values for a new computational algorithm / Christina Kouskouti ; Betreuer: Franz Kainer." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2018. http://d-nb.info/1170582702/34.

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Norda, Stephen [Verfasser], Thorsten [Akademischer Betreuer] Orlikowsky, and Ulrich [Akademischer Betreuer] Pecks. "Apolipoprotein E genotype in very preterm neonates with intrauterine growth restriction : an analysis of the German neonatal network cohort / Stephen Norda ; Thorsten Orlikowsky, Ulrich Pecks." Aachen : Universitätsbibliothek der RWTH Aachen, 2017. http://d-nb.info/1211590577/34.

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47

Burr, Laura Lynn. "Diet enrichment with arachidonic and docosahexaenoic acid during the lactation period attenuates the effects of intrauterine growth restriction from birth to maturity in the guinea pig and improves maternal bone mass." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=112384.

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Intrauterine growth restriction (IUGR) reduces bone mass by 10-30% and impairs arachidonic (AA) and docosahexaenoic (DHA) acid status in infants. Because AA and DHA enhance neonatal bone mass, the aim of this study was to determine the effects of dietary 0.5% AA and 0.2% DHA (w/w) prior to weaning on bone and growth. 40 guinea pigs were randomized to either a control (C) or low-protein diet (LP) during pregnancy and the C diet or the C diet with AA+DHA during lactation. Measurements included bone mass, metabolism, and strength, and erythrocyte lipid of sows and offspring from birth to 16 wk post-partum. The LP diet induced IUGR, while the AA+DHA increased bone mass by 5-20% in sows and offspring and corrected growth and bone mass in IUGR pups. Thus, AA+DHA provided in lactation rescues the growth trajectory in an IUGR state and is beneficial to maternal and neonatal bone mass.

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SOUSA, Silvia Helena Cavalcante de. "Catch-up de peso e índice de massa corporal em escolares de coortes de nascimento de duas cidades brasileiras." Universidade Federal do Maranhão, 2017. http://tedebc.ufma.br:8080/jspui/handle/tede/1848.

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Introduction: Intrauterine growth restriction (IUGR) and preterm birth (PT) are considered to be public health problems in developing countries. The occurrence of catch-up favors the ability of these infants to obtain equivalent growth to that of infants born without IUGR and at term. Objective: To assess the influence of IUGR and of PT on the occurrence of catch-up in weight and BMI in schoolchildren from two birth cohorts from cities with contrasting socioeconomic conditions in the Northeast and Southeast of Brazil. Method: A total of 1,463 children were studied, from whom information was collected at birth and at school age in 1994 and 2004/2005 in Ribeirão Preto, SP (RP) and in 1997/1998 and 2005/2006 in São Luís, MA (SL). The response variable was defined as the difference in weight and BMI between the Z-score of the schoolchild and the Z-score at birth. A change in Z-score ≥ 0.67 was considered to be catch-up. The explanatory variable was divided into four categories: without IUGR and at term (NIUGR-T), only IUGR (IUGR-T), only PT (NIUGR-PT), and PT plus IUGR (IUGR-PT). Estimates of the relative risk for catch-up in weight were obtained by logistic regression in separate models for each city. Results: RP children had a greater proportion of both catch-up than SL children. In RP, 90.8% of IUGR-PT and 70.8% of NIUGR-PT (it was more frequent in pre-terms, restricted or not) caught up in weight at school age. In SL, the NIUGR-PT and IUGR-T caught up in a similar way. There was no difference between genders. Regarding marital status, in RP, no difference was found, however, in SL, the odds of catching up at 7 years old was 65% lower for those schoolchildren whose mothers did not have a partner. Having only one child, both in RP and in SL, increased almost twofold (OR=1.89 in RP and 1.83 in SL) the odds of the schoolchild catching up; and receiving up to 5 times the monthly minimum wage decreased by 50% the odds of catching up in SL, although no difference was found in RP. The head of the family’s occupation being unqualified manual labor or unemployed decreased by half the odds of catching up in both cities. Maternal age and education level were not associated to catchup in school age. Conclusion: In both cities, children born preterm with/without IUGR had a greater proportion of catch-up in weight and without IUGR and at term in BMI.
Introdução: A restrição de crescimento intrauterino (RCIU) e o nascimento pré-termo (PT) são considerados problemas de saúde pública nos países em desenvolvimento. A ocorrência de catch-up propicia que estes consigam equiparar seu crescimento ao das crianças nascidas sadias. Objetivo: Avaliar a influência da RCIU e do PT na ocorrência de catch-up de peso e IMC em escolares de duas coortes de nascimentos de cidades com condições socioeconômicas contrastantes. Método: Foram estudadas 1.463 crianças, cujas informações foram coletadas ao nascer e na idade escolar em 1994 e 2005/06 em Ribeirão Preto, SP (RP) e em 1997/98 e 2005/06 em São Luís, MA (SL). A variável resposta foi definida pela diferença entre o escore z do escolar e escore z ao nascimento do peso e IMC. Considerou-se como catch-up uma mudança de escore z de ≥ 0,67. A variável explanatória foi dividida em quatro categorias: sem RCIU e a termo (TNR), só RCIU (TR), só PT (PTNR) e PT com RCIU (PTR). Estimativas do risco relativo para catch-up de peso foram obtidas por regressão logística em modelos separados por cidade. Resultados: O fenômeno “catch-up” tanto de peso quanto de IMC foi mais evidente em RP para todas as categorias das chamadas condições de nascimento. Para ambas as cidades a maior incidência de catch-up de peso se deu para os PT e/ou com RCIU, já o de IMC para os TNR. Não houve diferença entre os sexos. Ter somente 1 filho, maior renda familiar e escolaridade materna além da ocupação do chefe mais qualificada aumentou a frequência do catch-up de peso e IMC em ambas as cidades. Conclusão: Não só condições biológicas ao nascer mas também as condições de vida, tais como, acesso aos serviços de saúde e melhor oferta de alimentos nas idades mais precoces da criança influenciam na ocorrência de catch-up de peso e IMC nas duas cidades estudadas.

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Reis, Roberta Sena. "Efeito do consumo habitual de N-3 pufas sobre o comportamento alimentar e aspectos de sua regulação central em indivíduos com restrição de crescimento intrauterino." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2015. http://hdl.handle.net/10183/116785.

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Introdução: Nos seres humanos, a adversidade fetal está associada com escolhas alimentares menos saudáveis na idade adulta. Sabe-se que um menor crescimento fetal está relacionado à maior preferência por alimentos palatáveis e ao risco de obesidade. Ácidos graxos docosahexanoicos (DHA, ácidos graxos poli-insaturados ômega-3 - n-3 PUFAs) modulam o funcionamento do sistema mesolímbico dopaminérgico, envolvido nesse comportamento. Em ratos, nosso grupo evidenciou que o estresse neonatal interage com deficiência dietética leve de n-3 PUFAs, aumentando o risco para obesidade, resistência à insulina, precedido por hiperfagia na adolescência. Considerando o baixo peso ao nascer como marcador de exposição ao estresse metabólico crônico fetal, hipotetizou-se que o consumo de n-3 PUFAs pode interagir com o peso ao nascer e influenciar o comportamento alimentar. Objetivo: Verificar em dois estudos diferentes se o consumo habitual de n-3 PUFAs interage com o crescimento fetal (RCIU) e se interfere no comportamento alimentar e nos aspectos de sua regulação central em crianças e adolescentes/adultos jovens. Métodos: No estudo 1, a amostra incluiu 75 crianças das cidades de Montreal, Québec e Hamilton, Ontário, Canadá. Os participantes foram recrutados de uma coorte prospectiva de nascimentos já estabelecida (projeto MAVAN). O crescimento fetal foi com base na razão de peso ao nascer (BWR, peso ao nascer/média do peso ao nascer sexo-específica para cada idade gestacional da população local). Consideraram-se, tendo restrição de crescimento intrauterino (RCIU), as crianças com BWR<0,85. Aos 48 meses de idade, as mães preencheram um questionário de frequência alimentar; e, aos 72 meses, o Children’s Eating Behavior Questionnaire (CEBQ). Um modelo de regressão linear (General Linear Model - GLM) foi utilizado para avaliar a relação entre a RCIU e o consumo de n-3 PUFAs, aos 48 meses, e seu efeito nos escores do CEBQ, aos 6 anos de idade, considerando significativo um p<0,05. O projeto foi aprovado pelo Research Ethical Board do Douglas Mental Health Research Institute (n° 03/45). No estudo 2, a amostra incluiu 48 adolescentes/adultos jovens de Porto Alegre, RS. Os participantes foram recrutados de uma coorte prospectiva comunitária (projeto PROTAIA). A avaliação do crescimento fetal foi com base na BWR, e aqueles do tercil inferior da distribuição BWR foram considerados como RCIU. A concentração sérica de DHA (medida objetiva da ingestão de n-3 PUFAs) foi identificada por cromatografia gasosa. Os participantes preencheram o Dutch Eating Behaviour Questionaire (DEBQ). Um GLM foi realizado para avaliar a correlação entre a RCIU e o consumo de n-3 PUFAs e seu efeito nos escores do DEBQ, considerando significativo um p<0,05. As análises de Ressonância Magnética Funcional (fMRI), numa tarefa de visualização de alimentos palatáveis, não palatáveis e objetos neutros, tiveram como desfecho a ativação cerebral; e, como preditores, os valores contínuos dos níveis séricos de DHA e o BWR, utilizando uma regressão múltipla (FWE corrigido para comparações múltiplas com um p<0,05). O projeto foi aprovado pelo Comitê de Ética em Pesquisa do Hospital de Clínicas de Porto Alegre (n°12-0254). Resultados: No estudo 1, havia 40 meninas e 35 meninos. Não foram encontradas diferenças no consumo de n-3 PUFAs e outras variáveis de confusão entre indivíduos RCIU e não RCIU. No entanto, o GLM predizendo a “seletividade alimentar” aos 72 meses demonstrou uma interação significativa entre n-3 PUFAs e status de RCIU (sim/não) [Wald= 8,516; df=1; e p=0,004], com maior consumo sendo associado à diminuição da “seletividade alimentar” em crianças com RCIU. Não foram observados efeitos em outros domínios do CEBQ. No estudo 2, para a maioria das análises, havia 31 meninas e 16 meninos. Não foram encontradas diferenças nos níveis séricos de DHA e nas outras variáveis de confusão entre indivíduos RCIU e não RCIU. Somente o grupo com RCIU apresentou médias de peso ao nascer e do escore Z do IMC menores, quando comparado ao grupo não RCIU (p<0,0001 e p=0,046, respectivamente). O GLM predizendo “ingestão externa” evidenciou uma interação significativa entre a concentração sérica de DHA e status da RCIU (sim/não) [Wald=5,845; df=1; e p=0,016], com maiores níveis de DHA, sendo associados à diminuição do escore desse domínio em indivíduos com RCIU. Não foi observado efeito no domínio do DEBQ “ingestão emocional”, enquanto a “ingestão restritiva” não alcançou significância estatística [Wald=3,360; df=1; e p=0,067]. Na fMRI, tendo como preditores positivos e negativos, respectivamente, os níveis séricos de DHA e a razão de peso ao nascer (BWR), no contraste alimentos palatáveis>itens neutros, foi encontrada ativação cerebral no giro frontal superior direito (p corrigido=0,034). Ainda para esse contraste, tendo como preditor negativo apenas o BWR, a mesma região foi ativada (p corrigido=0,028), e ao considerar como preditores negativos ambos os níveis séricos de DHA e BWR, também foi encontrada ativação na mesma região cerebral (p corrigido=0,025). Os resultados de neuroimagem demonstraram que o BWR é um preditor mais importante, determinando, portanto, a ativação nessa região. Em outras palavras, quanto menor o BWR maior a ativação dessa região envolvida em controle de impulsos/tomada de decisão frente à visualização de imagens de alimentos palatáveis. Conclusões: Sugere-se que a restrição de crescimento intrauterino modula a ativação cerebral frente a estímulos relacionados a alimentos palatáveis, ativando uma área relacionada a controle de impulsos (giro frontal superior). Além disso, maior consumo de n-3 PUFAs pode proteger indivíduos com RCIU de comportamentos inadequados em diferentes idades, podendo beneficiar o comportamento alimentar infantil, bem como na adolescência/vida adulta, diminuindo a ingestão externa em resposta a estímulos alimentares externos.
Introduction: In humans, fetal adversity associates with less healthy food choices in adulthood. It is known that poor fetal growth is associated with an increased preference for palatable foods and obesity risk. Docosahexaenoic fatty acids (DHA, polyunsaturated fatty acids omega-3 - n-3 PUFAs) modulate the functioning of the dopamine mesolimbic system, which is involved in this behavior. In rats, our group showed that neonatal stress interacts with a mild dietary deficiency in n-3 PUFAs and increases the risk for obesity and insulin resistance, preceded by hyperphagia during adolescence. Considering low birth weight as a marker of chronic metabolic stress exposure, we hypothesized that n-3 PUFAs consumption could interact with birth weight and affect feeding behavior. Objective: We investigated in two different studies if the habitual consumption of n-3 PUFAs interacts with fetal growth (IUGR) and affects feeding behavior and aspects of their central regulation in children and adolescents/young adults. Methods: In study 1, the sample included 75 children from the city of Montreal, Quebec, and Hamilton, Ontario, Canada. Participants were recruited from an established prospective birth cohort (MAVAN project). Fetal growth was based on the birth weight ratio (BWR, birth weight/sex-specific mean birth weight for each gestational age), and children were considered intrauterine growth restricted (IUGR) if BWR<0.85. At 48-months of age, mothers completed a Food Frequency Questionnaire and at 72 months the Children’s Eating Behavior Questionnaire (CEBQ). A linear regression model (General Linear Model – GLM) was used to evaluate the correlation between IUGR and n-3 PUFAs consumption at 48 months and its effect on CEBQ scores at 6 years of age, considering statistically significant a p<0.05. The project was approved by the Research Ethical Board of the Douglas Mental Health Research Institute (n° 03/45). In study 2, the sample included 48 individuals from Porto Alegre, RS. Participants were recruited from a prospective communitarian cohort (PROTAIA project). Fetal growth was based on the BWR, and those in the lower tertile of the BWR distribution were considered IUGR. Serum DHA concentration (objective measure of n-3 PUFAs intake) was identified by gas chromatography. Participants filled out a Dutch Eating Behaviour Questionnaire (DEBQ). A General Linear Model (GLM) was used to evaluate the correlation between IUGR and serum DHA concentration and its effect on DEBQ scores, considering statistically significant a p<0.05. The Functional Magnetic Resonance Imaging (fMRI) analyzes in a task facing the visualization of palatable and non-palatable foods, as well as neutral objects had brain activation as the outcome, and the serum levels of DHA and BWR as continuous predictors, using a multiple regression (FWE corrected for multiple comparisons with p<0.05). The project was approved by the Research Ethical Board of the Hospital de Clínicas de Porto Alegre (n°12-0254). Results: In study 1, there were 40 girls and 35 boys. No differences were found on n-3 PUFAs consumption and other confounding variables between IUGR and non-IUGR individuals. However, the GLM model predicting food fussiness at 72 months showed a significant interaction between n-3 PUFAs and IUGR status (yes/no) [Wald= 8.516; df=1; p=0.004], with higher intakes being associated with decreased risk for food fussiness in IUGR children only. No effects were seen on the other domains of the CEBQ. In study 2, for most of the analyzes there were 31 girls and 16 boys. There were no differences in serum levels of DHA and other confounding variables between IUGR and non-IUGR individuals. However, the group with IUGR showed lower birth weight mean and BMI Z score when compared to the non-IUGR group (p<0.0001 and p=0.046, respectively). The GLM model predicting external eating showed a significant interaction between serum DHA concentration and IUGR status (yes/no) [Wald=5.845; df=1; p=0.016], with higher serum DHA concentration being associated with decreased external eating in the IUGR individuals. No effects were seen in the DEBQ domain emotional eating, while restrictive eating did not reached statistical significance [Wald=3.360; df=1; p=0.067]. In the fMRI, having as positive and negative predictors the serum DHA concentration and BWR respectively, in the contrast palatable foods>neutral objects we found an activation in the right superior frontal gyrus (p corrected=0.034). In this contrast, using only BWR as a negative predictor, the same area was activated (p corrected=0.028), and when considering as two negative predictors (serum DHA concentration and BWR), activation was found in the same brain region (p corrected=0.025). The fMRI results showed that BWR is a more important predictor determining activation of this brain region. In other words, the lower BWR (more IUGR), the more activation in this area involved in impulse control/decision making facing the visualization of palatable foods´ images. Conclusion: We suggest that IUGR modulates the brain activity facing stimuli related to palatable foods, activating an area related to impulse control (superior frontal gyrus). Moreover, higher intake of n-3 PUFAs can protect individuals with IUGR from inappropriate behaviors at different ages, decreasing food fussiness and the external eating in response to external food cues.

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Lamm, Katherine Young Bezold. "Mechanisms of Inverted formin 2-mediated intracellular trafficking, invasion, and placentation in mouse and human pregnancy." University of Cincinnati / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1521191444619542.

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