Dissertations / Theses on the topic 'Fertility diet'

Bakgrund: Infertilitet är en sjukdom i reproduktionssystemet som definieras av att en klinisk graviditet inte uppnås efter 12 månader eller mer av regelbundet oskyddat samlag. Cirka tio procent av par i fertil ålder världen över drabbas av ofrivillig barnlöshet. Hos ungefär 30 % av paren finns ingen förklaring till infertiliteten. Ofrivillig barnlöshet kan leda till långvarig kris och psykisk ohälsa. En god kosthållning kan ge olika hälsofördelar. Att vägleda och hjälpa dessa par med kostråd skulle kunna leda till bättre psykisk och fysisk hälsa samt ekonomiska besparingar för samhället. Syfte: Belysa kostens betydelse för fertiliteten. Metod: En systematisk litteratursökning. Databassökning genomfördes i CINAHL och PubMed  som resulterade i sju vetenskapliga artiklar. Resultat: Hemlagad mat, Medelhavsdiet, frukt & grönsaker, mjölkprodukter, kostfiber och omättat fett främjar fertiliteten. Socker, snabbmat och mättat fett är ogynnsamt för fertiliteten. Konklusion: Bevis har framkommit som tyder på att kosten har betydelse för kvinnors fertilitet. Implikation: En studie som finner ett resultat som påtalar att någon kost kan påverka fertiliteten kan utgöra grund för kostrådgivning som kan leda till färre fall av oönskad infertilitet och besparingar för samhället. Mer forskning inom området behövs.
Background: Infertility is a disease of the reproductive system defined by the fact that a clinical pregnancy is not achieved after 12 months or more of regular unprotected intercourse. Around ten percent of the fertile couples worldwide suffer involuntary infertility. In about 30 % of the cases there is no explanation for infertility. Involuntary infertility can lead to long-term crises and mental illness. A good diet can lead to better health. Helping these patients could lead to better mental health and physical health and economic savings for society. Purpose: To highlight the impact of the diet for fertility. Method: A systematic review. Database search was made in CINAHL and PubMed that resulted in seven scientific articles. Result: Homemade food, Mediterranean diet, fruits & vegetables, diary, dietary fiber and unsaturated fats are promoting fertility. Sugar, fast food and saturated fat are unfavorable for fertility. Conclusion: Evidence has emerged that the diet is important for women's fertility. Implication: A study that would find that a particular diet would have an impact on fertility could be useful in diet counselling that could lead to less cases of  infertility and  savings for society. More research in this area is needed.

Thesis (M.S.)--West Virginia University, 2002.
Title from document title page. Document formatted into pages; contains vi, 63 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 49-62).

This thesis deals with nutrition and diet, during the most fragile phases of life: fertility, pregnancy and hospitalized children. The duplex aim of this thesis is to investigate the dietary habits of subfertile couples attempting a pregnancy and the effects of bad nutrition on growth and metabolism in hospitalized children. It is divided into theoretical and experimental parts. The theoretical part studies firstly, the determinants of reproductive factors that influence male and female fertility and, secondly, the importance of maintaining a good nutritional status during hospital recovery in a pediatric population. The topic approached in this thesis belongs to a public health field since delivering and guarantee a good nutritional state in all ages of life is known to be crucial in the prevention of both under and overnutrition, which have both negative effects on long-term health. In the first experimental part, three studies that investigate data from a cohort of subfertile couples, presenting to the Infertility Unit of Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, are described. The aim is to analyze dietary and lifestyle habits of both males and females that may affect fertility. Dietary habits have been collected with the use of a previously validated Food Frequency Questionnaire. The results showed that a moderate alcohol intake appears associated with better semen quality in the male sample. While there is evidence to support that alcohol does have an impact on fertility, it is also difficult to establish a definitive link as there is no standard “drink” or comparative way to measure alcohol consumption. We could not analyze the role of heavy or binge drinking, which are consistently associated to detrimental effects on semen quality. Regarding female fertility, in literature there is evidence of a lower risk of in vitro fertilization failure in women reporting higher adherence to Mediterranean Diet. The analysis here described does not show a statistically significant effect of Mediterranean Diet on oocyte quality and success rate after assisted reproductive techniques. In the second experimental part, The Italian Pediatric Nutrition Survey which analyzed data from many Italian pediatric hospitals is presented, and metabolic data of children recovered in the Pediatric Unit of Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan are discussed. The aim of this this second part is to show how much pediatric malnutrition is still unrecognized in hospital setting, where, an accurate nutritional and metabolic evaluation should be recommended. Strong evidences suggest that nutrition modulates the capacity to exit from the state of stress and disease, with possible repercussions on growth and development and nutrition imbalances may affect the prognosis during hospital stay. In the national survey a high prevalence of both acute and chronic malnutrition among hospitalized pediatric patients in Italy emerges, especially in infants and young children and nutritional support is only given to a small number of the malnourished children. In disease condition, the metabolic response to stress is highly variable and cannot be easily predicted, consequently it is difficult to predict the right amount of calories and nutrients that a child needs starting from the calculation of the resting energy expenditure. In this thesis was demonstrated that the commonly employed equations, WHO, Harris-Benedict, Schofield, and Oxford formulae should not be used to estimate metabolism in hospitalized children. Feeding strategies based on these equations might result in unintended underfeeding or overfeeding. The development and validation of more accurate equations will be an initial step in precipitating a culture shift which places greater emphasis on the importance of nutritional delivery as a therapeutic intervention, rather than supportive care.

This thesis is concerned with how prehistoric infants were fed in different physical and cultural environments, and in particular what impact the economic, social, and epidemiological changes associated with the development of agriculture had on infant feeding practices. In order to examine these effects, stable isotope ratio analysis has been used to assess the duration of breastfeeding and weaning in a variety of prehistoric contexts. The first study is of Pitted Ware Culture hunter-gatherers at the site of Ajvide on Gotland, Sweden. Breastfeeding usually continued for at least two years, but there was some variation in supplementary foods, which is attributed to seasonal variations in resource availability. The second study analysed a number of Neolithic and early Bronze Age sites from south-east Poland. Breastfeeding duration varied both within and between sites and ranged from six months to five years. The third study found that the infant feeding practices of two Iron Age populations on Öland, Sweden, were very varied, and infants may have been fed differently depending on their social status. The fourth study is of the childhood diet in the Únětice Culture of south-west Poland. Individual diets changed little during the lifetime, suggesting that eventual adult identity was determined early in life. A small number of infants in the study were found to have breastfed for differing lengths of time. The final paper considers the health consequences of introducing animal milks into the infant diet in a prehistoric context, and finds that their availability is unlikely to have made it possible to safely wean infants earlier. Comparison of the results from the four stable isotope studies to those of other published studies reveals that the modal age at the end of weaning was slightly lower in agricultural communities than hunter-gatherer communities, but the range of ages was similar. Weaning prior to the age of eighteen months was rare before the post-medieval period. It is argued that the gradual reduction in breastfeeding duration since the Neolithic, and the replacement of breastmilk with animal milk products, means that on the whole the development of agriculture probably served to increase infant morbidity and mortality.

At the time of doctoral defense the following papers were unpublished and had a status as follows: Paper 1: Manuscript; Paper 4: Accepted; Paper 5: Forthcoming 2014

Lactase Persistence and the early Cultural History of Europe (LeCHE)

Thesis (MNutr)--Stellenbosch University, 2012.
ENGLISH ABSTRACT: The role of fructose restriction in addition to dietary modifications for weight loss and lifestyle improvement, on fertility outcome and other markers of metabolic syndrome, in obese women with polycystic ovarian syndrome (PCOS) Introduction: At the time at which the current study was undertaken no data, as yet, existed on whether restriction of fructose, while treating obese patients with PCOS for weight loss, improves the clinical symptoms and metabolic/anthropometric profile so as to promote fertility. Objectives: To evaluate the baseline intake of fructose, as well as the effect of restricting fructose intake from fruit and soft beverages to less than 20 g daily, as well as to provide guidelines for weight loss on anthropometric measurements, for improving subjective clinical symptoms, and for promoting fertility outcome in obese patients with PCOS, who seek to become fertile. Methods: The study was conducted in the Tygerberg Hospital Infertility Clinic, as an experimental cohort. Patients with a body mass index (BMI) higher than 27, seeking fertility after diagnosis with PCOS, were referred for dietary consultation, and followed up 3 monthly over 1 year. At each visit anthropometric measurements and a detailed dietary history were taken and a questionnaire for clinical symptoms was completed. Results: Baselinely, 86 patients were included in the study. Averages for weight and BMI were 99.8 ± 24.3 kg and 39.2 ± 8.7kg/m2, respectively. Average baseline daily fructose intake was 167 ± 116.8g. At baseline, significant relationships were shown between fructose intake and burning feet (ρ=0.02) and frequent waking (ρ=0.02), with a trend towards nightly eating (ρ=0.07). The dropout rate after visit 1 was 50%, with a further dropout of 41% after visit 2. After 3 visits (n=18), fructose intake significantly reduced (ρ=0.018), with the significant relationships with clinical symptoms having disappeared by visit 2. After 3 visits (n=18), both weight and BMI decreased significantly (ρ=0.017) and (ρ=0.019), respectively. Fructose was tested as a covariate to BMI, with high significance (ρ=0.006) in said population group. Conclusion: Dietary intervention to reduce fructose intake proved significant for weight loss and BMI after 3 visits. Reduced fructose intake was associated with reduced clinical symptoms. With fructose being a significant covariate to BMI, it can be concluded that fructose overconsumption could possibly contribute to both clinical symptoms and elevated BMI in said study population.
AFRIKAANSE OPSOMMING: Die rol wat die beperking van fruktose speel bykomend tot dieetaanpassings en lewenstylverbetering vir gewigsverlies by oorgewig vroue met polisistiese ovariële sindroom (PCOS) in die uitkoms van fertiliteit en ander merkers van metaboliese sindroom. Inleiding: Met die aanvang van hierdie studie was daar is geen data beskikbaar oor die invloed van die beperking van fruktose in die dieet van oorgewig pasiënte met PCOS wat vir gewigsverlies behandel word nie. Dit was ook nie bekend of laasgenoemde pasiënte se kliniese simptome en metaboliese/antropometriese profiel sou verbeter met die beperking van fruktose sodat fertiliteit by hierdie pasiënte terselfdertyd ook bevorder word nie. Doelwitte: Die evaluering van die aanvanklike inname van fruktose, sowel as die beperking van fruktose afkomstig van eetbare vrugte en versoete drankies en sap tot ’n inname van minder as 20 g daagliks, tesame met riglyne vir gewigsverlies. Die uitkoms hiervan is bepaal deur antropometriese metings, die verbetering in subjektiewe kliniese simptome en die fertiliteituitkoms by oorgewig pasiënte wat hulp met fertiliteit verlang. Metodes: Die studie het as ’n eksperimentele kohort by die Infertiliteitskliniek by Tygerberg Hospitaal plaasgevind. Pasiënte wat na diagnose met PCOS fertiliteitsbehandeling verlang het en ’n BMI hoër as 27 gehad het , is vir dieetbehandeling verwys en driemaandeliks oor ’n tydperk van een jaar opgevolg. Tydens elke besoek is antropometriese metings en ’n omvattende dieetgeskiedenis geneem en ’n vraelys oor kliniese simptome ingevul. Resultate: Aanvanklik is 86 pasiënte by die studie ingesluit. Gemiddeldes vir gewig en BMI was 99.8 ± 24.3 kg en 39.2 ± 8.7 kg/m2 respektiewelik. Gemiddelde aanvanklike daaglikse inname van fruktose was 167 ± 116.8 g. Oorspronklik het betekenisvolle verhoudings tussen fruktose en die volgende bestaan: brandvoete (ρ=0.02) en veelvuldige episodes van nagtelike wakkerheid (ρ=0.02), met ’n neiging na nagtelike etery (ρ=0.07). Die uitvalsyfer na een besoek was 50% met ’n verdere uitvalsyfer van 41% na die tweede besoek. Na drie besoeke (n=18) het sowel die gewig as die BMI betekenisvolle afname getoon (ρ= 0.017) en (ρ=0.019), respektiewelik. Fruktose is as ’n belangrike kovariant vir BMI (ρ= 0.006) vir hierdie populasiegroep geïdentifiseer. Gevolgtrekking: Dieetintervensie vir die vermindering van die inname van fruktose was beduidend vir gewigsverlies en afname in BMI na drie besoeke. Verminderde fruktose-inname het gelei tot die vermindering van kliniese simptome. Met fruktose as beduidende kovariant vir BMI kan die gevolgtrekking gemaak word dat die oor-inname van fruktose by hierdie studiepopulasie waarskynlik tot sowel kliniese simptome as BMI bygedra het.

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CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
A bionomia de Chelopistes meleagridis fora do hospedeiro foi observada com o objetivo de compreender aspectos relacionados ao ciclo de vida desta espécie. Para isto, adultos de C. meleagridis foram coletados e colocados em condições controladas para se reproduzir, oferecendo-se pena como alimento. Da prole destes adultos, foi observado o desenvolvimento de 150 indivíduos desde o ovo até a fase adulta. Para 75 destes, foi oferecida a dieta composta de pena, enquanto para os outros 75 a dieta foi composta de pena e pele do hospedeiro (peru, Meleagris gallopavo). Ao verificar que a dieta “pena + pele” foi a que resultou no maior número de adultos, foram observadas a fertilidade, fecundidade e a longevidade de piolhos criados in vitro desde o primeiro ínstar alimentados com esta dieta. Valores altos relacionados à reprodução desta espécie foram encontrados em relação a outros piolhos da subordem Ischnocera, destacando-se: número de ovos produzidos por dia e número de ovos produzidos por fêmeas durante a vida (médias de 2,54 e 26,61 ovos, respectivamente, para fêmeas selvagens e 2,11 e 29,33 ovos, respectivamente, para fêmeas criadas in vitro.). A inclusão de pele na dieta foi determinante para o desenvolvimento até o estágio adulto, uma vez que 48% dos piolhos alimentados com essa dieta atingiram a fase adulta. Quando foi oferecido apenas pena, 1,3% dos piolhos atingiram a maturidade. O tempo de desenvolvimento de machos e fêmeas foi semelhante (média de 29,38 dias) sem haver diferença na proporção sexual dos adultos.
Bionomics of the large louse turkey Chelopistes meleagridis off host was evaluated to comprehend aspects related to life cycle. To this, adults was collected and put in controlled conditions for reproduce, offered feathers as food. From offspring of these adults were observed the development of 150 lice from eggs to adults. To 75 of them was given only feathers as resource of food while to others 75 lice the diet was composed by feathers and skin debris from the natural host, Meleagris gallopavo. When verified that diet composed by feather + skin resulted in more adults, was evaluated fertility, fecundity and longevity of this specie reared in vitro from first nymphs to adults feed with this diet. High values related to reproduction of this specie were found in comparison with others avian Ischnocera, like: number of eggs produced by day and number of egg produced during the lifespan of females (means of 2.54 and 26.61, respectively to wild females and 2.11 and 29.33 respectively to females reared in vitro). The addition of skin in diet was determinant to development to adult stage, once time 48% fed with this diet reared to adults while the lice feed with feathers only 1.3 % of then became adult stage. The time of development of males and females was the same (29 days). The sex rate of adults reared in vitro was 1:1.

Contexte : Une amélioration des habitudes de vie, avec une légère perte pondérale (5 %), augmenterait les chances de concevoir un enfant chez les femmes obèses souffrant d’infertilité. La perte de poids est considérée comme le principal déterminant de la survenue d’une grossesse, mais aucune étude n’a évalué le rôle la qualité alimentaire. Objectif principal : Évaluer l’impact de l’amélioration de la qualité alimentaire sur les chances de survenue d’une grossesse auprès de femmes obèses et infertiles. Méthodologie : Étude prospective s’insérant dans un essai randomisé contrôlé évaluant l'impact d'une intervention interdisciplinaire visant l’amélioration des habitudes de vie sur la fertilité des femmes obèses suivies à la clinique de fertilité du CHUS en comparaison à des femmes ayant accès aux soins standards en fertilité seulement (n = 102). Des visites de recherche ont lieu à l’entrée de l’étude puis aux 6 mois jusqu’à la fin du projet, soit après 18 mois ou jusqu’à l’accouchement. La collecte de données inclut un questionnaire de fréquence alimentaire, des mesures anthropométriques et un test de condition physique. Un index de qualité alimentaire, le Healthy Eating Index modifié (mHEI, 0-100 points), a été calculé. Résultats : Pour l’ensemble des participantes, l’amélioration de la qualité alimentaire n’était pas associée à de meilleures chances de grossesse. À l’aide d’un modèle de régression de Cox, il a été possible d’observer que la qualité alimentaire initiale était un prédicteur important de grossesse au sein des deux groupes confondus (HR (par 10 unités) : 1,24 [1,03 – 1,50], p = 0,027), indépendamment du niveau de condition physique et de l’anthropométrie. De façon similaire, une meilleure qualité alimentaire observée avant conception présentait une association significative indépendante avec les chances de concevoir dans le temps (HR (par 10 unités) : 1,25 [1,04 – 1,49], p = 0,017). Les variables anthropométriques, incluant le poids, n’étaient pas associées à une probabilité accrue de concevoir. Conclusion : Une meilleure qualité alimentaire en préconception augmenterait les chances de grossesse chez les femmes infertiles souffrant d’obésité.
Abstract : Background : Improvement of lifestyle habits, associated with a modest weight loss (5 %), has shown to increase odds of pregnancy in overweight and obese women diagnosed with infertility. Weight loss is considered as the main factor that explains the improvement of fertility, but no study evaluated the specific role of diet quality on fertility in this population. Objective : Evaluate the impact of improving diet quality on odds of pregnancy in obese and infertile women seeking for fertility treatments. Methods : Prospective study nested in a randomized controlled trial evaluating the impact of an interdisciplinary lifestyle intervention on fertility of obese women followed at the fertility clinic of the CHUS, in comparison to standard fertility care only. Research visits take place every 6 months until the end of the project, which is after 18 months or delivery. Data collection include a food frequency questionnaire, anthropometric measurement and a fitness evaluation. A score of diet quality, the modified Healthy Eating Index (mHEI, 0-100 units), was calculated. Results : For all the participants, improvement of diet quality was not associated with the probability of pregnancy. With Cox regression, we observed that the initial diet quality was an important predictor of pregnancy within the two confounded groups (HR (by 10 units) : 1.24 [1.03 – 1.50], p = 0.027), independently of cardiorespiratory fitness and anthropometry. Similarly, the best diet quality observed before conception presented a significant independent association with odds of pregnancy over time (HR (by 10 units) : 1.25 [1.04 – 1.49], p = 0.017). Anthropometric variables, including weight, were not associated with a higher probability of conception. Conclusion : A greater diet quality in preconception seems to increase probability of pregnancy in obese infertile women.

Pregnancy loss remains a major source of economic cost to the equine industry. Frequently, the exact causes of pregnancy loss remain unknown. It has been shown, in other species, that increased dietary protein leading to elevated blood urea nitrogen concentrations (BUN) can be a factor in decreased survival of the early embryo. Our studies provided novel information regarding the effects of elevated BUN on endometrium and embryos from mares as well as insights on changes in their gene expression. Our first objective was to develop an experimental model to elevate BUN during diestrus using intravenous urea infusion. We analyzed the effects of an acute elevation in BUN on uterine and vaginal pH along with changes in the endometrial transcriptome of mares with RNA sequencing. There was a significant increase in BUN and a decrease in uterine pH in the urea group compared to the control group. A total of 193 genes were differentially expressed (DEG) between the urea and control groups. The DEG were predicted to be related to cell pH, ion homeostasis, changes in epithelial tissue, fatty acid metabolism, and solute carriers. Our second objective was to evaluate the effects of elevated BUN in the endometrium of mares using a chronic oral urea administration to elevate BUN in mares. Uterine and vaginal pH were evaluated and RNA sequencing of the endometrium was again performed. There was an increase in BUN in the urea-fed mares, but no significant change in uterine or vaginal pH between the groups. A total of 60 DEG were characterized, with prediction of transcriptomic changes in the endometrium of mares related to cell death (necrosis) and cellular movement (invasion of cells). Our third objective was to determine the effects of a high BUN on the transcriptome of day-14 embryos. There was a positive correlation between plasma BUN and blastocoele fluid urea nitrogen concentration. Changes in embryo transcriptome were related to survival of organism, angiogenesis, adhesion, and quantity of cells. Our final objective was to evaluate the correlation between BUN and follicular fluid urea nitrogen and evaluate the survival of embryos collected from donor mares with high BUN concentrations. Urea nitrogen concentration was positively correlated between the plasma and follicular fluid of mares. Additionally, there was a higher pregnancy rate when embryos were collected from mares with lower BUN. Overall, these results further elucidate the mechanisms through which urea affects endometrial and embryonic transcriptome of mares with high BUN, serving to identify effects of a high BUN in the reproductive tract of mares that might lead to decreased fertility.

L'érosion de la biodiversité prairiale est devenue une préoccupation majeure à l'échelle Européenne. Le pâturage ovin est supposé avoir un impact négatif sur la diversité prairiale, en raison de leur forte sélectivité pour les dicotylédones, indispensables aux insectes pollinisateurs. Comparés aux bovins, les ovins structurent peu les couverts et créent également moins de niches écologiques contrastées. L'objectif de cette thèse était de tester la faisabilité, et les bénéfices en pâturage ovin, d'une conduite en rotation dans laquelle une sous-parcelle est temporairement exclue du pâturage au moment du pic de floraison. Les effets de cette conduite ont été comparés à ceux d'un pâturage continu au même chargement. Au delà des indicateurs directs de performances zootechniques et de biodiversité (plantes, papillons, bourdons et carabes), nous avons analysé la sélection alimentaire des brebis dans les deux modes de conduite. Nous avons aussi cherché à appréhender comment la race et la fertilité du milieu pouvaient moduler la faisabilité d'un tel pâturage tournant et son intérêt vis-à-vis de la préservation de la biodiversité. Indépendamment de leur race, les brebis ont présenté une sélection alimentaire accrue vis-à-vis des dicotylédones dans les parcelles pâturées en rotation, qui a rapidement entraîné une diminution de leur richesse floristique en comparaison des parcelles pâturées en continu. L'augmentation de l'intensité de floraison des sous parcelles temporairement exclues de la rotation a favorisé les bourdons, probablement en raison de l'augmentation de la ressource en pollen et en nectar. En revanche, ce mode de gestion n'a pas permis d'augmenter la densité ni la richesse spécifique des papillons et des carabes. Le bénéfice d'une mise en défens temporaire d'une partie des parcelles semble donc moindre qu'en pâturage bovin. Définir les dates de mises en défens par rapport à la floraison d'espèces indicatrices, moduler la durée de la mise en défens en fonction de la pousse de printemps, et prolonger l'exclusion de certaines parcelles en automne et en hiver sont autant de pistes qu'il nous reste à explorer, afin de déterminer les conditions d'application optimale d'une telle conduite.

Inledning Generella riktlinjer för kost och hälsa har historiskt utformats utifrån forskning på män, vilket resulterat i att kvinnor i fertil ålder ofta blivit missförstådda, misstolkade och felbehandlade. Låggradig inflammation, snabbmat och den moderna livsstilen, misstänks vara grund för flera sjukdomar vilka övervägande drabbar kvinnor. Syftet med studien var en kartläggning och kritisk granskning av forskning på hälsa och ohälsa hos kvinnor i fertil ålder relaterad till kosthållning. Metod Studien är en litteraturöversikt över tio artiklar fokuserade på kvinnor i fertil ålders hälsa och ohälsa i relation till kost. Artiklarna har systematiskt analyserats och sammanfattats. Resultat Resultatet visade att kvinnors fertilitet, inträdet av klimakteriet, premenstruella besvär och sjukdomar tycks relaterade till fysiska obalanser och inflammation samt påverkas av kostval. Gula och gröna grönsaker och frukter, fibrer, vegetabiliskt protein och antiinflammatorisk kost var att föredra för goda hälsoeffekter. Diskussion Kostens betydelse för fertilitet och hälsa hos kvinnor i fertil ålder var tydlig och sammanlagda effekter av nutrienter i kost verkar överträffa enskilda tillskott. Kunskapsspridning och mer forskning är essentiell för att stärka gruppens hälsa, främja empowerment samt möjliggöra goda bio-psyko-sociala effekter.
Introduction General diet and health guidelines have historically been designed based on research on men, with the result that women of childbearing age have often been misunderstood, misinterpreted and mistreated. Low-grade inflammation, fast food and modern lifestyle, is thought to be the basis of several diseases predominantly afflicted by women. The purpose of the study was a survey and critical review of health and ill health research in women of childbearing age related to dietary choices. Method The study is a literature review of ten articles focusing on health and ill health of women at child bearing age in relation to diet. The articles have been systematically analyzed and summarized. Results The results showed that women's fertility, the onset of menopause, premenstrual disorders and diseases appear to be related to physical imbalances and inflammation and were affected by dietary choices. Yellow and green vegetables and fruits, fiber, vegetable protein and an antiinflammatory diet displayed extra beneficial health effects. Discussion The importance of diet for fertility and health in women of childbearing age was clear and the combined effects of nutrients in diet appear to exceed individual supplements. Knowledge dissemination as well as research is essential for strengthening the group's health, promoting empowerment as well as make room for good bio-psycho-social effects.

Les graisses alimentaires consommées influencent la composition lipidique du plasma et du tissu adipeux, la concentration plasmatique des hormones stéroïdiennes ainsi que la fluidité des membranes cellulaires. Une alimentation riche en graisses génère un stress oxydatif qui conduit à des phénomènes de peroxydation lipidique. En effet, il a été démontré que le cholestérol favorise la production de radicaux libres tandis que la vitamine E est un puissant antioxydant. Le stress oxydatif est connu pour perturber la stéroïdogenèse, d'autre part certains acides gras sont capables de stimuler l’apoptose dans les cellules de Leydig. Par ailleurs, la consommation de régimes hyper-lipidiques influence également la fertilité par l’intermédiaire de la leptine. Dans ce travail, nous avons étudié l’effet de régimes hyper-lipidiques (supplémenté avec du cholestérol et/ou de la vitamine E) sur la sécrétion et le métabolisme des androgènes, le niveau d’apoptose dans les testicules et la prostate. Nous avons caractérisé le niveau d’expression du gène ob (codant pour la leptine) et de la GSTα dans les testicules, des récepteurs testiculaires et prostatiques aux androgènes (AR), les concentrations plasmatiques des gonadotropines (LH et FSH), testostérone, œstradiole et HDL. Nos travaux démontrent qu’une alimentation hyper-lipidique module la stéroïdogenèse testiculaire, l’expression des protéines pro- et antiapoptotique, les ARs au niveau des testicules et de la prostate ainsi que le taux d’ARNm du gène ob dans les testicules. En conclusion, nos résultats montrent que la consommation de régimes riches en graisses perturbe les fonctions gonadique et prostatique
Dietary fatty acids consumption affects plasma lipid and adipose tissue composition, steroid hormone concentration in plasma; they may change also cell membrane fluidity. High-fat diets generate an oxidative stress via free radical surproduction which induce lipids peroxydation. Oxidative stress disturbs testicular steroidogenesis, moreover some fatty acids are able to induce Leydig cells apoptosis. In the other side it was already showed that vitamin E plays an antioxidant-protecting role while cholesterol favours free radicals production. In addition hyperlipidic diets intake seem to affect fertility by leptin mediation. The goal of this work was to determine influence of high-fat diets, its fatty acids composition and cholesterol and/or vitamin E supplementation on androgens secretion and metabolism and characterise theirs effect on programmed cell death in testes and prostate. We have examined also ob gene expression (coded for leptin) and GSTα protein level in testis, androgen receptor expression (AR) in testis and prostate as well as gonadotropines (LH, FSH), sex hormones (estradiol, testosterone) and HDL fraction of cholesterol levels in plasma. The present work show that high-fat diets intake can modulate testicular steroidogenesis, influence on protein pro- and antiapoptotic and AR levels in testis and prostate and on ob gene mRNA level in testis. These results confirm therefore that dietary lipids with or without cholesterol and/or vitamin E addition can disturb testis and prostate functions

The objectives of this study were to assess growth and reproductive performance of boars fed a diet supplemented with organic selenium (Se). Crossbred boars received one of three treatments: I. basal diet with no supplemental Se, II. basal diet supplemented with 0.3 ppm organic Se (Sel-Plex), and, III. basal diet supplemented with 0.3 ppm sodium selenite. Nursery (n = 13 pens/treatment) boar performance was not affected (P > 0.1) by diet and only grow-finish (n = 11 pens/treatment) G:F was greater (P < 0.06) for Sel-Plex (0.378) compared with selenite (0.368) or control (0.363) boars. At 15-mo of age semen was collected from boars (n = 10/treatment) over 5-d. Semen quality declined over time, but the negative impact day had on sperm motility was less pronounced with Sel-Plex boars. Effects of treatment x day were detected for progressively motile (P = 0.02) and rapidly moving (P = 0.03) spermatozoa, sperm path velocity (VAP; P = 0.05), and average velocity (VSL; P = 0.05). At 17-mo of age, semen was collected from boars (n = 10/treatment), extended and stored over 10-d. Although semen quality decreased over time, sperm from Sel-Plex boars resisted the negative effects of day on sperm motility and pH. Effects of treatment x day were detected for percent motile spermatozoa (P < 0.01), static spermatozoa (P < 0.01), VAP (P = 0.06), amplitude of head displacement (ALH; P = 0.02), straightness (P = 0.01), and pH (P < 0.01). At 23-mo of age, semen was collected (day 0) from boars (n = 6/treatment), extended, stored and evaluated at d 1 and 8 using in vitro fertilization. Dietary Se treatment failed to affect (P < 0.05) in vitro fertilizing rates of boars. In summary, dietary supplementation with Sel-Plex enhanced G:F in grow/finish boars. Dietary Sel-Plex supplementation may decrease the effects that stressors, such as intensive semen collection or semen storage, have on boar sperm characteristics such as sperm motility. The mechanisms for these responses remain to be elucidated.
Ph. D.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Algumas espécies, como a perdiz (Rhynchotus rufescens), não apresentam informações bem definidas sobre a sua alimentação em cativeiro, portanto é necessária a realização de pesquisas visando a determinação de suas exigências nutricionais. Estes trabalhos tiveram como objetivo determinar o melhor nível de proteína bruta e avaliar a suplementação de quatro níveis de selênio orgânico sobre características reprodutivas de machos e fêmeas na fase reprodutiva de perdizes (Rhynchotus rufescens). Nos dois experimentos as aves foram alojadas em galpão avícola convencional, divididas em 16 boxes, em quartetos, compostos por um macho e três fêmeas. A alimentação foi fornecida em comedouros tubulares, com ração peletizada composta principalmente por milho e farelo de soja. Foram usadas quatro dietas na fase de reprodução, todas com o mesmo nível de energia metabolizável (2800 kcal/kg), no primeiro trabalho utilizou-se quatro níveis de proteína bruta 15, 18, 21 e 24% de PB, no segundo experimento o mesmo nível de proteína em todas as rações (22,5%) e quatro diferentes níveis de selênio orgânico 0; 0,2; 0,4 e 0,8 ppm. Os dados obtidos foram analisados pelo método dos quadrados mínimos. Recomenda-se, o nível de 22,5% de proteína bruta nas rações de postura para melhorar o peso e a espessura da casca do ovo de perdizes (Rhynchotus rufescens) e a adição de selênio orgânico (Sel-Plex®) não proporcionou alteração nas características reprodutivas de machos e fêmeas de perdizes (Rhynchotus rufescens)
Rhynchotus rufescens not have enough information on diets in captivity, so it is necessary to determine the nutritional requirement for this species. These experiments aimed at studying crude protein requirement and testing four levels to organic selenium supplementation in the laying period of red winged tinamous diet. The birds were located in a conventional avian barn divided in 16 compartments with four animals, one male and three females. The food was supplied in cylindrical feeders with pelletized ration based on corn and soybean. Four rations were used having the same metabolized energy content (2800 kcal/kg), in the first experiment were used four different protein levels: 15, 18, 21 and 24%, in the second experiment four diets were used having the same protein level (22.5%) and four different selenium levels: 0, 0.2, 0.4 and 0.8 ppm. Data was analyzed by the least square method. The level of 22.5% CP showed better eggs weight and shell thickness and the addition of organic selenium (Sel-Plex®) did not change the reproductive traits of males and females in red-winged tinamous (Rhynchotus rufescens)

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
The gossypol is a Polyphenolic yellow pigment (C30H30O8), toxic that is present in all parts of cotton plant and its derivatives. Experiments show the reproductive side effects caused by feed containing high percentage of bran or cottonseed and claim that gossypol might affect in different ways the reproductive system, causing sperm abnormalities and subsequent infertility. In this work, it was examined the effects caused by diet rich in cottonseed containing gossypol on hair sheep ram semen Santa Inês Breed. The work was performed with 22 rams, sexually mature, which were divided into 2 groups, being the animals confined in individual stocks. The gossypol group (Gg = 15), was supplemented with 500g of gossypol cottonseed and the control group (Gc = 7), supplemented with 500g of corn. The two groups were supplemented during 104 days and underwent semen collections, by the method of artificial vagina and measurements of scrotal circumference (C.E.), before (7 days), during (at intervals of 15 days) and after (10 days) the supplementation period. Non o statistical difference was seen in the mean C.E. group being treatment and control group respectively 27.07 cm and 27.08 cm. The variable observed in the semen were: color, aspect, volume, whirling, motility, concentration, vigor and sperm morphology. For color and aspect analyses were qualitative and no differences were seen in these parameters. The mean for seminal volume for animals who consumed cottonseed was 1.04 ml and for control group was 0.94 ml with no significant difference. In the variable whirling, motility, vigor, concentration and morphology there was no statistical difference and the results was respectively 4.12-81.6%-4.26-3.57 x 109/ml sptz – 6.7% and 3.91 control group – 74.77%-4.07-3.48 x 109 sptz/ml-5.97%. After the last semen collection 5 animals from gossypol group and 2 animals from control group was submitted to unilateral orchiectomy. The material was used to perform the comparative Histopathological examination in historesin, No difference in seminiferous tubule diameter was seen between control and gossypol group. There was a significant difference in seminiferous epithelium height, having a larger measurement at gossypol epithelium compared with control group. The height of seminiferous epithelium is an effective feature for sperm production assessment, however in this study there was no significant difference in sperm concentration between control and treatment group demonstrating that this difference did not affect sperm production. Two out of the three castrated animals from gossypol group were used as a fertility test exposing them to 10 fertile ewes during 90 days, resulting in 6pregnancies. The results showed that supplementation with cottonseed gossypol rich-diet did not influence sperm quality, testicular morphology, fertilization capacity and seminiferous tubules morphology.
O gossipol é um pigmento polifenólico amarelo (C30H30O8), de natureza tóxica que está presente em todas as partes do algodoeiro e em seus derivados primários. Experimentos realizados mostram os efeitos colaterais na reprodução causadas por rações contendo alta porcentagem de farelo ou caroço de algodão e afirmam que o gossipol pode afetar de maneira multiforme o sistema reprodutivo, causando anormalidade nos espermatozoides e consequente infertilidade. Nesse trabalho foram analisados os efeitos causados pela dieta rica em caroço de algodão contendo gossipol no sêmen de ovinos deslanados da Raça Santa Inês. Para isso, o trabalho foi desenvolvido com 22 ovinos machos, em idade reprodutiva, os quais foram divididos em dois grupos, sendo os animais confinados em baias individuais. O grupo gossipol (Gg = 15), suplementado com 500g de caroço de algodão e o grupo controle (Gc = 7), suplementado com 500g de milho. Os dois grupos foram suplementados durante 104 dias e foram submetidos a coletas de sêmen, pelo método da vagina artificial e aferições de circunferência escrotal (C.E.), antes (7dias), durante (em intervalos de 15 dias) e depois (14 dias) do período de suplementação. Não houve diferença estatística na média de circunferência escrotal (C.E.) sendo a média do grupo tratamento e do grupo controle respectivamente 27,07 cm e 27,08 cm. As variáveis observadas no sêmen foram: coloração, aspecto, volume, turbilhonamento, motilidade, concentração, vigor e morfologia espermática. Para coloração e aspecto as análises foram qualitativas e não foram observadas diferenças nessas variáveis. A média do volume seminal para os animais que consumiram caroço de algodão foi de 1,04 ml e para os que não consumiram foi de 0,94 ml. Nas variáveis de turbilhonamento, motilidade, vigor, concentração e morfologia não houve diferença significativa sendo os valores do grupo tratamento respectivamente 4,12 – 81,6% - 4,26 – 3,57 x 109sptz /ml – 6,7% e do grupo controle 3,91 – 74,77% – 4,07 – 3,48 x 109sptz/ml – 5,97%. Após o término da última coleta de sêmen cinco animais sofreram orquiectomia unilateral, sendo dois do grupo controle e três do grupo gossipol. O material foi utilizado para realização de exame histopatológico comparativo em historesina, onde não apresentou diferença significativa entre tratamento e controle quanto ao diâmetro de túbulo seminífero, e apresentou diferença na altura do epitélio seminífero. Tendo o grupo gossipol maiores medidas de epitélio do que o grupo controle. A altura do epitélio seminífero é uma característica efetiva para a avaliação da produção espermática, entretanto nesse estudo não houve diferença significativa na concentração espermática entre grupo controle e tratamento demonstrando que essa diferença não afetou a produção espermática. Dois dos três animais castrados do grupo gossipol foram utilizados para um teste de fertilidade, onde cobriram 10 ovelhas férteis durante 90 dias, resultando em 6 prenheses positivas. Os resultados da pesquisa mostram que a suplementação com caroço de algodão não influenciou a qualidade espermática, a morfometria testicular, a capacidade fertilizante dos espermatozoides e a morfologia dos túbulos seminíferos.

Resumo: Algumas espécies, como a perdiz (Rhynchotus rufescens), não apresentam informações bem definidas sobre a sua alimentação em cativeiro, portanto é necessária a realização de pesquisas visando a determinação de suas exigências nutricionais. Estes trabalhos tiveram como objetivo determinar o melhor nível de proteína bruta e avaliar a suplementação de quatro níveis de selênio orgânico sobre características reprodutivas de machos e fêmeas na fase reprodutiva de perdizes (Rhynchotus rufescens). Nos dois experimentos as aves foram alojadas em galpão avícola convencional, divididas em 16 boxes, em quartetos, compostos por um macho e três fêmeas. A alimentação foi fornecida em comedouros tubulares, com ração peletizada composta principalmente por milho e farelo de soja. Foram usadas quatro dietas na fase de reprodução, todas com o mesmo nível de energia metabolizável (2800 kcal/kg), no primeiro trabalho utilizou-se quatro níveis de proteína bruta 15, 18, 21 e 24% de PB, no segundo experimento o mesmo nível de proteína em todas as rações (22,5%) e quatro diferentes níveis de selênio orgânico 0; 0,2; 0,4 e 0,8 ppm. Os dados obtidos foram analisados pelo método dos quadrados mínimos. Recomenda-se, o nível de 22,5% de proteína bruta nas rações de postura para melhorar o peso e a espessura da casca do ovo de perdizes (Rhynchotus rufescens) e a adição de selênio orgânico (Sel-Plex®) não proporcionou alteração nas características reprodutivas de machos e fêmeas de perdizes (Rhynchotus rufescens)
Abstract: Rhynchotus rufescens not have enough information on diets in captivity, so it is necessary to determine the nutritional requirement for this species. These experiments aimed at studying crude protein requirement and testing four levels to organic selenium supplementation in the laying period of red winged tinamous diet. The birds were located in a conventional avian barn divided in 16 compartments with four animals, one male and three females. The food was supplied in cylindrical feeders with pelletized ration based on corn and soybean. Four rations were used having the same metabolized energy content (2800 kcal/kg), in the first experiment were used four different protein levels: 15, 18, 21 and 24%, in the second experiment four diets were used having the same protein level (22.5%) and four different selenium levels: 0, 0.2, 0.4 and 0.8 ppm. Data was analyzed by the least square method. The level of 22.5% CP showed better eggs weight and shell thickness and the addition of organic selenium (Sel-Plex®) did not change the reproductive traits of males and females in red-winged tinamous (Rhynchotus rufescens)
Orientadora: Sandra Aidar de Queiroz
Coorientadora: Vera Maria Barbosa de Moraes
Banca: Danísio Prado Munari
Banca: Valquíria Hyppólito Barnabé
Mestre

Orientador: Wilma De Grava Kempinas
Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: O sobrepeso e a obesidade estão aumentando rapidamente, tornando-se uma epidemia mundial. Estas duas condições podem ser definidas simplesmente como o acúmulo excessivo de gordura nos adipócitos, células do tecido adiposo responsáveis pela síntese e liberação de leptina, um hormônio protéico cuja principal ação é inibir o apetite e estimular o gasto energético, mas que também atua na regulação do eixo hipotalâmico-hipofisáriogonadal. As concentrações séricas de leptina apresentam-se elevadas, proporcionalmente à quantidade de gordura, em muitos modelos animais de obesidade e na obesidade humana. Recentemente alguns estudos têm mostrado a relação entre obesidade e infertilidade masculina, mas até o momento os resultados são controversos. Da mesma forma, o papel da leptina no sistema reprodutor masculino não está muito esclarecido, principalmente quando este hormônio está em excesso, como na obesidade. Assim, os objetivos do presente estudo foram investigar os efeitos da obesidade induzida por consumo de dieta rica em gordura em parâmetros reprodutivos de ratos machos. Também foi investigado o papel da leptina na fertilidade e em alguns parâmetros espermáticos, em ratos machos adultos. Para isso, ratos machos da variedade Wistar foram alimentados com dieta hipercalórica rica em gordura (DH) ou com dieta padrão (DP) durante 15, 30 ou 45 semanas, e foram avaliados quanto ao índice de obesidade, níveis séricos de leptina, peso dos órgãos reprodutores e contagens espermáticas. Em um segundo experimento, os animais receberam as diferentes dietas apenas por 15 semanas, tempo suficiente para provocar obesidade. Esses animais foram avaliados quanto às dosagens dos hormônios sexuais, comportamento sexual, motilidade e morfologia espermática, fertilidade após cruzamento natural e inseminação artificial in utero. Além disso, ratos machos adultos não-obesos foram tratados com leptina exógena, ou com salina, ip, por 42 dias e avaliados quanto ao peso dos órgãos reprodutores, contagens espermáticas, motilidade dos espermatozóides e fertilidade após inseminação artificial. Após 15, 30 ou 45 semanas, os animais alimentados com DH apresentaram um aumento significativo no índice de obesidade e nos níveis de leptina. O peso dos órgãos reprodutores e as contagens espermáticas foram similares entre os dois grupos, em todos os períodos estudados. Nos animais que receberam DH por 15 semanas, o comportamento sexual e a fertilidade após acasalamento natural foram semelhantes aos do grupo controle. Da mesma forma, os níveis de testosterona não foram alterados, mas os de estradiol aumentaram nos animais que ingeriram DH. Além disso, a qualidade espermática foi reduzida nestes animais, como evidenciado pela baixa porcentagem de espermatozóides com movimento progressivo. A alteração da motilidade espermática foi seguida por uma redução quantitativa do potencial de fertilidade após inseminação artificial in utero. Os animais tratados com leptina não apresentaram diferenças nas contagens espermáticas nem na motilidade quando comparados aos animais controle. No entanto, o potencial de fertilidade reduziu cerca de 40% e a taxa de perdas pré-implantação foi duas vezes maior nos animais tratados com leptina. Juntos, esses resultados indicam que a obesidade diminuiu a qualidade espermática, prejudicando a fertilidade dos ratos machos, e que, provavelmente a leptina está relacionada a este prejuízo
Abstract: Overweight and obesity are rapidly becoming a worldwide epidemic that affects children and adults. These two statuses are often defined simply as a condition of abnormal or excessive fat accumulation in adipose tissue, whose cells are responsible for synthesis and release of leptin. This is a protein hormone whose main action is to decrease appetite and increase energy expenditure, but it also act as regulatory signal for gonadal axis, among other functions. Serum leptin concentration is augmented in several obesity animal models and in obese human, proportionately to the amount of fat. Some studies have shown a relationship between obesity and male infertility, but until now it remains controversial. In the same way, the role of leptin on male reproductive function is not clear, mainly when the hormone is in excess as occur in obesity. Thus, the aims of the present study were to investigate the effects of high-fat diet-induced obesity on male rats' reproductive parameters. Furthermore it was evaluated the possible role of the excess of leptin on fertility and some sperm parameters in adult male rats. To achieve these aims, male Wistar rats were fed a high-fat diet (HFD) or standard chow (SD) for 15, 30 or 45 and were evaluated by adiposity index, serum leptin levels, reproductive organ weights and sperm counts. In a second experiment rats received HFD or SD only for 15 weeks, long enough to cause obesity. Sexual hormones, sexual behavior, sperm morphology and motility, fertility after natural mating and after artificial in utero insemination were evaluated. Moreover, non-obese adult male rats were treated with exogenous leptin ip (30?g/kg/day) or vehicle for 42 days and were evaluated for sperm count in testis and epididymis, sperm motility and fertility after in utero artificial insemination. After 15, 30 or 45 weeks, HFD-fed animals presented significant increases in obesity index and serum leptin levels. Reproductive organ weights and sperm counts in the testis and epididymis were similar between the two groups at all timepoints studied. In HFD-fed animals only for 15 weeks, sexual behavior and fertility after natural mating were not altered by the diet regimen. In these animals, intergroup testosterone levels were also comparable, but estradiol levels were increased in HDF rats. Furthermore, sperm quality was reduced in 15 weeks HFD-fed animals as evidenced by their decreased percentage of sperm with progressive movement. This altered motility parameter was followed by a quantitative reduction in fertility potential after artificial in utero insemination. Leptin treated animals did not show any differences in sperm counts either in the testis or epididymis. In the same way, the percentage of progressive, non-progressive and immotile sperm was similar between the two groups. However, the fertility potential showed a reduction of about 40% whereas the pre-implantation loss rate increased more than two fold in leptin treated animals. These results indicate that obesity lead to a decrease in sperm quality, impairing male fertility and probably the excess of leptin is related with this alteration of fertility
Doutorado
Biologia Celular
Doutor em Biologia Celular e Estrutural

The present study was to evaluate the reproductive performance of broiler breeders fed different levels of protein and metabolizable energy treated with three different diets, varying amounts of metabolizable energy and crude protein. In one treatment, the heavy broiler breeders were fed a diet with 13.8% CP and 2750 Kcal / kg, 22 to 66 weeks of age. In treatment two, the roosters received the same ration provides for the females, being from 22 to 36 weeks of age containing 15% CP from 36 to 60 weeks, 15.2% CP and 60 to 66 weeks, 14% CP, all diets contained 2850 Kcal / kg. In treatment three, the breeding males fed a diet with15% CP and 2700 Kcal / kg from 22 to 66 weeks is old. The semen was collected from 16 rooster each treatment in three different ages of week, 34, 38, 43, 48 and 51 weeks. The semen collected was subjected to staining protocol with toluidine blue and subsequently evaluated by computer image analysis, with measurements of area, perimeter, homogeneity and intensity of compaction of chromatin in each head of spermatozoa. The roosters fed with high protein (15%) showed improve results in terms of compression and density of the heads of sperm chromatin. This same group had values of spermatozoa size smaller, which indicates minor morphological changes. It wasn t possible to correlate the onset and fertility with other data, as in this study there was no significant difference between treatments (p >0.05). Concerning the age of the rooster, regardless of the diet used, all treatments showed changes in chromatin compaction, and the roosters fed with 13.8% crude protein and 2750 Kcal / kg, showed greater changes in chromatin compaction. This can explain the decrease in fertility, usually observed in the field after this period, in flocks of broiler breeders.
O presente estudo teve como objetivo avaliar a morfometria e a compactação de cromatina em espermatozóides de reprodutores tratados com diferentes níveis de proteínas, e comparar as análises de compactação de cromatina com fertilidade e eclodibilidade, analisando a eficiência reprodutiva de galos reprodutores de corte. No tratamento um, os galos reprodutores pesados, foram alimentados com uma ração com 13,8% de Proteína Bruta (PB) e 2750 Kcal de EM/Kg, de 22 a 66 semanas de idade. No tratamento dois, os galos receberam a mesma ração fornecida para as fêmeas, sendo das 22 a 36 semanas de idade contendo 15% de PB, das 36 a 60 semanas, 15.2% de PB e das 60 a 66 semanas, 14% de PB, todas as dietas continham 2850 de Kcal de EM/Kg. No tratamento tres, os machos reprodutores foram alimentados com uma ração 15% de PB e 2700 Kcal de EM/Kg, de 22 a 66 semanas de idade. O sêmen de 16 galos foi coletado de cada tratamento, em três idades diferentes: 34, 38, 43, 48 e 51 semanas. O sêmen coletado foi submetido a protocolo de coloração com azul de toluidina, e posteriormente avaliado por análise de imagem computacional, com mensurações da área, perímetro, homogeneidade e intensidade da compactação da cromatina dentro de cada cabeça do espermatozóide. Os galos alimentados com elevado nível de proteína (15%) apresentaram melhores resultados em relação à compactação e a homogeneidade da cromatina das cabeças dos espermatozóides. Este mesmo grupo apresentou valores de tamanho de espermatozóides menores, o que indica menores alterações morfológicas. Não foi possível correlacionar a eclosão e fertilidade com os demais dados, pois neste estudo não houve diferença significativa entre os três tratamentos (p>0.05). Em relação à idade do galo reprodutor, independente da dieta utilizada, todos os tratamentos apresentaram alterações na compactação da cromatina, sendo que os galos alimentados com 13.8% de proteína bruta e 2750 Kcal de EM/Kg, apresentaram maiores alterações na compactação da cromatina. O que pode explicar a queda na fertilidade, geralmente observada no campo, após este período, em plantéis de matrizes pesadas.
Mestre em Ciências Veterinárias

Generational ritual abuse within satanic or fertility (abusive witchcraft) cults is a controversial subject. This study shows that, while not all reported memories may be true, False Memory Syndrome is not an intrinsic scientific reality of generational ritual abuse. Recent publications under the editorial pens of Noblitt and Perskin Noblitt (2008), as well as Sachs and Galton (2008), describe the types of abuse and torture perpetrated in various forms of ritual abuse (including the results of a worldwide survey), together with the psychological, interpersonal and spiritual damage it caused survivors. It also speaks of the legal difficulties of survivors, the motives of perpetrators and the difficulties experienced with disappearing evidence (sometimes deliberately, otherwise because it does not fit the known legal paradigm). Survivors of generational ritual abuse suffer from what can be described under DESNOS (Disorders of Extreme Stress - Not Otherwise Specified), which is supported by research whilst not yet a formal DSM diagnostic category. Prolonged interpersonal trauma, involving multiple events lead to alterations of affect and impulses: in attention or consciousness; in self-perception; in relationships with other; in systems of meaning; as well as somatisation. Most often it results in dissociative disorders of which the most common is DID (Dissociative Identity Disorder) in which a person exhibits two or more distinct identities or personality states which recurrently take control of his or her behaviour. Various other diagnostic-related factors are discussed in this study, together with major paradigms for considering DID. These paradigms include the ego-state theory (referred to briefly), structural dissociation and attachment theory. These models' intervention strategies are also discussed. Models from three Christian psychologists are discussed - those of Joubert, Friesen and Wilder (a community model) - and Hawkins and Hawkins' pastoral model is reviewed as well. "The fear of the Lord" is found to be the reverential awe with which a believer approaches God; linked closely to the love of God; a fear that is advocated over the fear of human enemies or circumstances and which then dispels the latter; an emotion of fear that is experienced when confronted, as sinful human being, with God's presence and attributes such as his holiness; advocated by Jesus and Paul as based upon God's judgment, after which he may cast one into hell - and thus, one is not to fear what man could do unto one, or should not depart from God and continue in wilful sin. Ps. 86 contains a prayer for a united heart that the psalmist may fear God, linked to walking in his truth and praising God for deliverance from the grave. While "the fear of the Lord" is not a healing model in and of itself (various models of intervention can be used in the healing journey as found in the literature study), it guides the stance of the community, the pastoral counsellor (or other helper) as well as the survivors of generational ritual abuse who turn to God. It was found to form a doorway into the covenant relationship (or intimate relationship) with God in Scripture, and it is argued that, as such, it will help to lead survivors away from negative or destructive fear-bonded relationships (in Wilder's terms) into love-bonded relationships with God and others, thus leading to fulfilment of the command 'to love God with all one's heart, soul and strength and others as oneself' (Dt. 6; Mrk. 12:29-31). To this end, it aids the pastoral healing goal of a growing relationship with God and increasing maturity. Using the models of Heitink, Osmer and Hurding, the insights gained in this study are applied to the guidelines and proposed model for pastoral intervention.
Thesis (M.A. (Pastoral)--North-West University, Potchefstroom Campus, 2011.

Diese Arbeit ist ein Beitrag zur Entwicklung einer Strategie für die eine CO2 sparende zu- künftige Landwirtschaft, in der nur geringe Emissionen von Treibhausgasen entstehen, die Stromerzeugung vor Ort aus natürlichen Ressourcen erfolgt, eine maximale Ausnutzung der Sonnenenergie genutzt wird, und der Konflikt zwischen der Nutzung der verfügbaren Ressourcen für Nahrungsmittel und Treibstoff Produktion vermieden wird. Alle Versuche in der Arbeit wurden in den Jahren 2005 -2009 auf der Öko-Farm (TOSOLY) der UTA (Fundación para la Producción Agropecuaria Tropical Sostenible Capitulo Kolumbien - UTA) unter der Leitung von Dr. TR Preston (Präsident ) und MSc Lylian Rodríguez (Director) durchgeführt.
This thesis is a contribution to the strategy that should underpin all future farming systems: namely the need to “de-carbonize” the system, by reducing emissions of greenhouse gases, generating electricity locally from natural resources, making maximum use of solar energy and ensuring there is no conflict between use of available resources for both food and fuel production. All the experiments described in the thesis were carried out in the period 2005 -2009 at the ecological farm (TOSOLY) of the UTA Foundation (Fundación para la Producción Agropecuaria Tropical Sostenible Capitulo Colombia – UTA) of which the principals are Dr T R Preston (President) and MSc Lylian Rodríguez (Director).

Obesity has dramatically increased in the population in the last few decades, and data from the Australian Bureau of Statistics National Health Survey indicates that currently approximately half of the women in Australia are overweight or obese. The fact that many of these women are in their reproductive years is concerning. Obesity increases the risk of developing chronic diseases as well as having a negative effect on women’s reproductive health, influencing the prevalence of subfertility, infertility and pregnancy complications. Polycystic Ovary Syndrome (PCOS) is the most common reproductive disorder in women and it is closely related to obesity. It is characterized by acyclicity, anovulation and increased levels of androgens in blood, as well as decreased rates of pregnancy. Increased BMI has been associated with dysregulated menstrual cycles, anovulation or oligo-ovulation, and lower pregnancy rates. Recent evidence suggests that obesity causes the initiation of a pro-inflammatory state that extends to the adipose, liver, and muscle tissues. The increased release of proinflammatory cytokines from adipose tissue, such as interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α), induces lipolysis, enhances cytokine release, and promotes insulin resistance. At the cellular level, it is characterized by mitochondrial dysfunction and the activation of stress pathways, namely Endoplasmic reticulum (ER)-stress and the Heat Shock Response (HSR). The different stress responses constitute a complex network that interacts not only with nascent polypeptides and stress-denatured proteins, but also with metabolic (insulin), hormonal (steroid hormones and their receptors) and immunological pathways (antigen presentation). That these pathways also affect ovarian function makes HSP a potential target for therapeutic interventions in obesity. However, it is still not clear how obesity influences the ovarian environment, and how this affects stress pathways in ovarian cells, as well as its impact on oocyte homeostasis and the development of the preimplantation embryo. Thus, I will explore how different factors impact the obesity phenotype in female mice, with special emphasis on ovarian function and the expression of stress responses in ovarian cells, and ultimately how they affect oocyte quality and developmental potential. For this, I will be using three different mouse models of obesity, namely a Dihydrotestosterone (DHT) -induced PCOS model, a High fat diet (HFD) -induced model and a High Sugar High Fat combination diet. Finally, I will determine if specific chaperone-inducing micronutrients can promote the induction of these cytoprotective HSP and/or normalize ER stress, in order to identify a natural fertility-protective diet.
Thesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 2019

Male overweight/obesity effects 70% of the adult Australian population with this rate 10% higher (80%) in men attending a South Australian fertility clinic, suggesting a link between male overweight/obesity and sub fertility. Male obesity alters the molecular structure of sperm, increasing sperm DNA damage and reactive oxygen species (ROS) and altering mitochondrial function. This perturbed sperm function leads to altered embryo quality (reduced blastocyst development, blastocyst cell numbers and blastocyst mitochondrial function) which subsequently reduces implantation and live birth rates. Rodent models of male obesity have further implicated male obesity in the development of adult chronic diseases, increasing the susceptibility of obesity, diabetes and sub fertility in offspring across two generations. Limited published research has assessed the reversibility of male obesity induced sub fertility. Due to limitations inherited in human studies, the aim of this thesis was to establish if obesity induced sub fertility could be reversed utilising a rodent model of male obesity with short term diet and/or exercise interventions for proof of concept. Male mice were fed a high fat diet (HFD) containing 21% fat or a control diet (CD) containing 6% fat for a period of 8-10 weeks to increase adiposity, following HFD exposure mice were allocated to one of four treatment groups 1) diet intervention (HC, change to CD), 2) exercise intervention (HE, continuation of a HFD with 3 x 30 min swimming sessions a week), 3) combined diet/exercise intervention (HCE, change to a CD with swimming exercise) or 4) continuation of a HFD (HH) for a further 8-10 weeks. Mice allocated to the CD continued on the CD (CC) for intervention period. Diet intervention with (HCE) or without (HC) exercise reduced bodyweight, adiposity, and serum cholesterol while exercise intervention alone (HE) maintained their original level of adiposity. All interventions had improvements to serum glucose and leptin regulation while exercise subsequently improved serum free fatty acids and C - reactive protein. All interventions restored sperm function (motility, morphology, mitochondrial function, ROS and DNA damage levels). Males were subsequently mated with super ovulated normal weight females for assessment of embryo quality. All interventions restored blastocyst cell numbers and day 18 fetal weights while, exercise with (HCE) or without (HE) as CD further restored embryo development. As early embryo and fetal health are predictors of subsequent offspring health, males were also mated with naturally cycling normal weight females to produce offspring. Diet intervention alone (HC) showed the biggest restorations to male offspring sperm function (motility, sperm binding, capacitation and mitochondrial function). In contrast, exercise intervention alone (HE) showed the biggest restoration to female offspring metabolic health (glucose and insulin sensitivity and adipose accumulation) while the remaining interventions (HC and HCE) had minimal impact. The improvements to female offspring metabolic health from exercise interventions in their fathers may be related to their partial restoration of sperm X-linked microRNA abundance (i.e. mir-503 and mir-465b-5p), with these microRNAs specifically targeting pathways important for early embryo development including cell cycle control and apoptosis. Together these studies provided some of the first evidence for the reversibility of obesity related fertility issues in males, highlighting that it may be more about restoring systematic metabolic health rather than a reduction in adiposity, with the deciphering an epigenetic mechanism in sperm for transmission of effects to the embryo and offspring phenotypes. These studies will undoubtedly stimulate further research into other related molecular mechanisms and the independent associations between obesity related metabolic changes and their relationships with male fertility.
Thesis (Ph.D.) -- University of Adelaide, School of Paediatrics and Reproductive Health, 2014

RESUMO: Nas últimas décadas a prevalência mundial de doenças metabólicas como a obesidade e a diabetes mellitus tipo 2 (T2DM) tem aumentado exponencialmente, sendo atualmente uma séria preocupação de saúde, social e económica. Este aumento é paralelo ao aumento do sedentarismo e dos maus hábitos alimentares. De facto, a industrialização e a urbanização levaram ao aumento do consumo de alimentos com alto teor de hidratos de carbono e lípidos. A dieta, juntamente com a predisposição genética, são os principais causadores de desregulação metabólica, que acaba por levar ao aparecimento de complicações metabólicas em vários órgãos, como é o caso do fígado, músculo, tecido adiposo e testículo. O fígado tem um papel fundamental para a regulação da homeostase da glicose. No estado pósprandial, o fígado converte a glicose circulante em glicogénio. Por outro lado, no estado de jejum, a glicose é produzida a partir do glicogénio armazenado para manter os níveis de glicose em circulação dentro dos limites normais. De facto, a homeostase sistémica da glicose e da insulina é fortemente regulada por uma rede neuronal e hormonal. A insulina tem um papel central no controlo do metabolismo hepático, estimulando a glicólise e a lipogénese, enquanto suprime a produção endógena de glicose e de corpos cetónicos. Qualquer desequilíbrio no metabolismo energético do fígado pode levar a desregulações no metabolismo da glicose e da insulina e resistência à insulina, levando ao aparecimento de esteatose hepática não alcoólica (NAFLD) e T2DM. Sabe-se ainda que a T2DM e a disglicémia afetam vários sistemas, como o sistema reprodutor masculino. De facto, há uma maior prevalência de subfertilidade/infertilidade em indivíduos com diabetes. Para além disso, a glicose, a insulina e os lípidos têm um papel fundamental no controlo do metabolismo testicular. Efetivamente, as células de Sertoli dependem da glicose em circulação para produzir lactato, o substrato energético usado pelas células germinativas em desenvolvimento. Assim, o metabolismo das células testiculares é crucial para a ocorrência normal de espermatogénese e qualquer desregulação pode levar à diminuição da fertilidade. O objetivo geral deste trabalho foi o de contribuir para o entendimento da regulação homeostática do metabolismo da insulina, glicose e lípidos em estados metabólicos alterados, como obesidade e resistência à insulina. Primeiramente, avaliámos o metaboloma do fígado, músculo e tecido adiposo castanho no contexto de uma alimentação com alto teor de gordura ou frutose durante 12 semanas, abrangendo a fase equivalente à puberdade e à idade adulta. Os nossos resultados mostram que uma dieta rica em gordura durante 12 semanas causou aumento do peso, intolerância à glicose e resistência à insulina, enquanto a dieta rica em frutose durante o mesmo período de tempo levou à diminuição do peso corporal e não causou alterações na tolerância à glicose. Embora as dietas tenham efeitos distintos no ganho de peso corporal e tolerância à glicose, ambas causaram alterações significativas no metaboloma dos tecidos. No entanto, a dieta rica em gordura afetou de modo mais pronunciado o metaboloma do fígado e do músculo, enquanto a dieta rica em frutose afectou mais o metaboloma do tecido adiposo castanho. Além disso, ambas as dietas levaram a uma diminuição significativa na expressão de PON1. Tendo isso em conta, avaliámos o impacto da deleção de Pon1 nas consequências metabólicas da ingestão de uma dieta normal, dieta rica em gordura ou dieta rica em frutose. Neste estudo, a deleção de Pon1 levou ao aumento da intolerância à glicose em murganhos alimentados com dieta normal ou com uma dieta rica em gordura. Além disso, a ausência de PON1 levou ao aumento do péptido-C sem alterações nos níveis de insulina em todas as dietas, o que aponta para uma diminuição da clearance da insulina ou diminuição da excreção do péptido-C. Em termos de deposição lipídica no fígado, não foram encontradas diferenças por conta da deleção de Pon1, independentemente da dieta. Considerando os resultados anteriores, foi realizada uma análise de clusters em indíviduos normoglicémicos, com pré-diabetes ou T2DM para verificar se a atividade paraoxonase da PON1 (POase) e os níveis de apolipoproteína J poderiam melhorar o diagnóstico de dismetabolismo, ajudando a refinar e desvendar clusters com significado fisiopatológico distinto. Esta análise de clusters identificou quatro grupos. Um deles agrupou os indivíduos jovens e aparentemente saudáveis e, portanto, sem disglicémia nem dislipidémia e com alta POase. Outros indivíduos foram agrupados num grupo maioritariamente caracterizado por disglicémia, hiperinsulinémia e dislipidémia. Os restantes grupos apresentaram perfis intermédios de insulina e glicose em comparação com os dois primeiros grupos. No entanto, estes grupos apenas se distinguiam entre si pela POase. Sendo assim, a nossa hipótese é de que esses indivíduos com menor atividade da POase mas sem disglicémia significativa, tenham uma de duas condições: i) polimorfismos de Pon1 que resultam em baixa atividade POase e / ou ii) doença renal, resultando em disfunção do colesterol HDL, representada por baixa atividade de POase, sendo que esta última vai de encontro aos resultados obtidos no modelo animal com a deleção de Pon1. Embora se saiba que a desregulação da insulina e da glicose afetam a função reprodutiva masculina, os mecanismos exatos permanecem amplamente desconhecidos. Assim, avaliámos o impacto da hiperinsulinémia na função reprodutiva masculina. Para isso, usamos um modelo animal com deleção do gene que codifica para a enzima degradadora da insulina (IDE), levando a que os animais desenvolvam hiperinsulinémia. Os nossos resultados mostram que murganhos sem IDE apresentam uma morfologia testicular comprometida. Para além disso, estes animais também apresentam uma redução na qualidade espermática, nomeadamente da viabilidade e alterações na morfologia dos espermatozoides. Assim, este estudo mostra que a IDE desempenha um papel importante na determinação do potencial reprodutivo masculino. Em conclusão, este trabalho demonstrou que dietas ricas em gorduras e em frutose têm um impacto diferente, não apenas homeostase da glicose e da insulina, mas também nos tecidos sensíveis à insulina. Para além disso, os níveis hepáticos de PON1 foram afetados por essas dietas. Usando um modelo animal geneticamente modificado, foi demonstrado que a PON1 desempenha um papel na homeostase sistémica da glicose, sem afetar o ganho de peso. Após uma análise de clusters utilizando a atividade da POase, juntamente com o perfil lipídico e a função renal para informar a análise, verificou-se que a atividade da POase pode ser um valioso co-biomarcador para refinar perfis dismetabólicos com um significado fisiopatológico possivelmente distinto. Por fim, a IDE, por ter um papel na homeostase da insulina, contribui para a regulação da função reprodutiva masculina.Agrupados, os estudos que compõem esta dissertação demonstram que a PON1 e a IDE desempenham um papel na patogénese das co-morbilidades associadas à obesidade à pré-diabetes.
ABSTRACT: In the last decades the worldwide prevalence of metabolic diseases, as obesity and type 2 diabetes mellitus (T2DM), has exponentially increase posing as a serious health, social and economic concern. This increase parallels the increase of sedentarism and overnutrition. In fact, industrialization and urbanization led to the increased consumption of foods with high-carbohydrate and fat content. These, along with genetic predisposition, are the foremost contributors to metabolic dysregulation, namely hyperglycemia, dyslipidemia, and insulin resistance (IR), which ultimately lead to the onset of metabolic complications in several organs, such as the liver, muscle, adipose tissue and testes. The liver has a key role for the regulation of whole-body glucose homeostasis. In the fed state, liver uptakes and converts circulating glucose into glycogen. On the other hand, in the fasted state, glucose is produced in from stored glycogen to maintain circulating glucose levels within normal ranges. Indeed, both glucose and insulin whole-body homeostasis are tightly regulated by a neuronal and hormonal network. Insulin has a pivotal role in controlling hepatic metabolism, by stimulating glycolysis and lipogenesis while suppressing endogenous glucose production and ketogenesis. Any imbalance in the liver energy metabolism is a major contributor to overall glucose and insulin dysmetabolism, insulin resistance, and ectopic lipid accumulation ultimately leading to the onset of non-alcoholic fatty liver disease (NAFLD) and T2DM. T2DM and dysglycemia are known to affect several systems, as is the case of male reproductive system. Indeed, there is a higher prevalence of subfertility/infertility in individuals with diabetes. In fact, glucose, insulin and lipids have a key role in controlling the testicular metabolism. Moreover, Sertoli cells depend on circulating glucose to produce lactate, the energetic substrate used by developing germ cells. Thus, the metabolism of testicular cells is crucial for the normal occurrence of spermatogenesis and any dysregulation may lead to decreased fertility. The overall goal of this research work was to contribute to the understanding of the homeostatic regulation of insulin, glucose and lipid metabolism in altered metabolic states such as obesity and IR. Firstly, we assessed the metabolome of liver, muscle and brown adipose tissue in the context of highfat or high-fructose feeding for 12 weeks, covering the phase equivalent to puberty and adulthood. Our results demonstrate that a 12-week high-fat diet caused increased weight gain, glucose intolerance and insulin resistance, whereas high-fructose led to decreased body weight and did not lead to alterations in glucose tolerance. Although the diets had distinct effects on body weight gain and glucose tolerance, both led to significant alterations in the tissue’s metabolome. However, highfat diet affected more the metabolome of liver and muscle, while high-fructose diet seemed to affect more the brown adipose tissue. Moreover, both high-fat and high-fructose diet caused a significant decrease in the hepatic protein levels of PON1. Thus, the impact of whole-body Pon1 deletion upon the intake of normal chow, high-fat or high-fructose diets was evaluated. In this study, Pon1 deletion led to increased glucose intolerance in mice fed with normal chow diet or high-fat diet. Moreover, the absence of PON1 led to increased C-peptide levels with no changes in insulin levels of the diet, which points towards either decreased insulin clearance or impaired C-peptide excretion. In terms of ectopic lipid deposition, no differences where found upon Pon1 deletion regardless of the diet. Considering the previous results, a cluster analysis was performed in individuals with normoglycemia, prediabetes or T2DM, to evaluate whether PON1 paraoxonase (POase) activity and apolipoprotein J levels could improve the diagnosis of dysmetabolism, helping to refine and unveil clusters with distinct pathophysiological significance. In fact, the cluster analysis identified four clusters. One with the considered healthy and young individuals, and thus without dysglycemia, dyslipidemia and with high POase. Other cluster grouped individuals with dysglycemia, hyperinsulinemia, and dyslipidemia. The other two clusters presented intermediate insulin and glucose profiles compared with the first two clusters. However, these two groups were distinct in relation to POase activity. We hypothesize that these individuals with lower POase activity but without significant dysglycemia have one of two conditions: i) PON1 polymorphisms that result in low POase activity and/or ii) kidney disease, resulting in high-density lipoprotein cholesterol dysfunction that is represented by low POase activity. This last hypothesis goes in accordance with the results of Pon1 knockout model. Although it is known that insulin ang glucose dysregulation affects male reproductive function, the exact mechanisms by which insulin dysfunction mediates these effects remain largely unknown. Thus, we assessed the impact of primary hyperinsulinemia on male reproductive function. For that, we used a whole-body knockout model for Ide, the insulin-degrading enzyme (IDE). In the absence of IDE, insulin is not degraded in the liver, leading to hyperinsulinemia. Our results show that knockout mice for Ide mice present impaired testicular morphology. Moreover, these mice also present impaired sperm quality, namely a decrease in both sperm viability and morphology. Thus, this study provides evidence that IDE plays an important role in determining the reproductive potential of males. In conclusion, this research work demonstrated that high-fat and high-fructose diets have a different impact not only in overall glucose and insulin homeostasis, but also on insulin-sensitive tissues. Moreover, hepatic PON1 levels were found to be affected by these diets. By using a genetically modified mouse model, it was demonstrated that PON1 plays a role in glucose homeostasis, without affecting weight gain. After performing a cluster analysis in individuals with normoglycemia, prediabetes or T2DM, using POase activity along with lipid profile and renal function to inform the analysis, it was found that POase activity might be a valuable co-biomarker to refine dysmetabolic profiles with potentially different pathophysiological meaning. Lastly, IDE, by having a role in insulin homeostasis, contributes to a normal male reproductive function. Together, the individual studies that compose this dissertation demonstrate that PON1 and IDE play a role in the pathogenesis of obesity and prediabetes-associated co-morbidities.

A sobrevivência do ser humano reside numa fertilidade saudável, no entanto, nos últimos anos tem-se observado um declínio na fertilidade masculina. Este problema tem particular incidência nas sociedades modernas, e a curto prazo estará presente nos países em desenvolvimento. Factores externos associados ao estilo de vida, tais como maus hábitos alimentares, particularmente a ingestão excessiva de dietas de alta energia, têm contribuído para o aumento de doenças metabólicas, nomeadamente a obesidade e a diabetes mellitus (DM). Na verdade, a combinação de factores como: mudanças na composição de alimentos; aumento do consumo de dietas de alta energia; consumo de alimentos com altos níveis de açúcar e gorduras saturadas de elevada palatibilidade; o sedentarismo e a falta de atividade física são a principal causa para o incremento destas patologias. A obesidade e a DM são problemas de saúde pública nos países desenvolvidos e a sua incidência tem vindo a aumentar rapidamente entre os homens em idade reprodutiva, contribuindo para o surgimento da subfertilidade e infertilidade nesses indivíduos. A desregulação metabólica e endócrina associada a estes estadios patológicos compromete a função reprodutora masculina, uma vez que o eixo hipotálamo-hipófise-testículo, também conhecido como eixo reprodutivo, é sensível a alterações metabólicas. O tecido testicular é composto por uma população heterogénea de células somáticas e germinativas. As células germinativas estão dependentes do apoio nutricional fornecido pelas células de Sertoli, e distúrbios metabólicos podem perturbar essa cooperação metabólica. O metabolismo das células testiculares, em particular o das células de Sertoli, apresenta características únicas, uma vez que estas células são capazes de metabolizar vários substratos (e.g.: glucose, ácidos gordos, corpos cetónicos). As células de Sertoli metabolizam preferencialmente a glucose, sendo que a maioria desta é convertida a lactato, e não oxidada através do ciclo de Krebs. Os mecanismos que regulam o metabolismo das células de Sertoli são essenciais para a espermatogénese, e este processo metabólico é controlado por vários fatores, entre eles a insulina e as hormonas esteróides sexuais. Doenças metabólicas, como a DM, apresentam na sua origem resistência à insulina e/ou ausência de insulina, bem como uma incapacidade de as células responderem de forma eficiente à estimulação por esta hormona. Dada a importância da insulina no metabolismo da glucose e o facto de as células de Sertoli expressam receptores específicos para esta hormona, avaliámos o comportamento metabólico das células de Sertoli em situações de privação de insulina. Nestas condições, as células de Sertoli alteram o seu metabolismo glicolítico, diminuíndo a taxa de produção de lactato através da modulação da expressão de proteínas associadas à produção e exportação de lactato, sugerindo que são afectadas na sua actividade metabólica em condições patológicas associadas à desregulação da insulina, como é o caso da DM. No entanto, a DM induz uma desregulação endócrina generalizada. Uma consequência directa da DM na função testicular é a inibição da síntese de testosterona (T). Neste trabalho, demonstramos que os esteróides sexuais, particularmente a testosterona (e o seu metabolito 5α-di-hidrotestosterona) e o 17β-estradiol (E2), modulam o metabolismo glicolítico das células de Sertoli, favorecendo o consumo de glucose, sem contudo promoverem a síntese de lactato. De facto, a produção de lactato, que é o principal substrato para o desenvolvimento das células germinativas, encontrava-se diminuída pela acção androgénica, o que poderá resultar num comprometimento da cooperação metabólica testicular. Quanto mais severo é o estado de progressão da DM, maior é a redução dos níveis da T. Desta forma, estudámos os efeitos da desregulação dos níveis da T induzidos por diferentes estadios da DM, pré-diabetes e diabetes mellitus tipo 2 no metabolismo glicolítico das células de Sertoli. Os resultados mostraram que quanto mais avançado é o estado da doença, mais a via glicolítica está comprometida, verificando-se igualmente uma alteração mais acentuada na maquinaria celular associada à produção de lactato em células em cultura com níveis de T associados à diabetes mellitus tipo 2. Curiosamente, as células de Sertoli em cultura em condições de T similares ao observado no estado de diabetes mellitus tipo 2 mostram que são capazes de adoptar mecanismos que promovem o uso de substratos alternativos, como é o caso do glicogénio. Ao nível do testículo, evidenciou-se que o estado de pré-diabetes induzido pelo consumo de dietas de alta energia também altera o metabolismo glicolítico. Nestas condições, a via glicolítica está favorecida devido ao aumento da expressão e actividade de proteínas essenciais que intervêm nessa via metabólica. Também a expressão de proteínas associadas à produção de lactato está aumentada, o que parece contribuir para o aumento observado no lactato testicular. No entanto, e apesar da adaptação metabólica evidenciada, os parâmetros reprodutivos são seriamente afectados, o que pode resultar do favorecimento de um ambiente testicular oxidativo. De facto, nessas condições observou-se uma diminuição significativa da expressão de proteínas envolvidas tanto na manutenção da biogénese mitocondrial, como na activação do sistema de defesa contra as espécies reactivas de oxigénio. O potencial antioxidante testicular diminuído, assim como, a alteração na respiração mitocondrial testicular contribuíram igualmente para uma deficiente capacidade bioenergética e um aumento do ambiente oxidativo. Já em estadios mais avançados da DM, como é o caso da diabetes mellitus tipo 2, observou-se que o metabolismo glicolítico testicular é seriamente comprometido. A actividade da lactato desidrogenase está severamente diminuída, contribuindo para uma diminuição do conteúdo em lactato neste tecido. Porém, nestas condições destaca-se a adaptação verificada no metabolismo testicular, que promoveu um aumento do conteúdo de glicogénio nos testículos. Estes resultados indicam que a diabetes mellitus tipo 2 induz uma reprogramação metabólica testicular, promovendo vias metabólicas alternativas. No entanto, os parâmetros espermáticos dos indivíduos que sofriam desta condição estavam comprometidos, visto que a motilidade e viabilidade dos espermatozóides estavam acentuadamente diminuídas e o número de espermatozóides com anomalias na morfologia era elevado. Em conclusão, este trabalho demonstra que as doenças metabólicas, particularmente a DM, podem contribuir para uma diminuição do potencial reprodutivo masculino induzindo alterações profundas no metabolismo celular do testículo, e em particular no metabolismo das células de Sertoli. O processo da espermatogénese é complexo e, do ponto de vista fisiológico, o metabolismo glicolítico é essencial para o sucesso deste evento celular. A regulação do metabolismo da glucose nas células de Sertoli é alvo de vários factores, e tanto nos estadios iniciais da DM, como nos estadios mais avançados, sofre alterações, sendo que são mais pronunciadas em estadios avançados da doença. De facto, verificou-se que em estadios iniciais da DM o metabolismo testicular tende a adaptar-se de modo a assegurar a produção de lactato para as células germinativas em desenvolvimento. Todavia com a progressão da doença, a produção desse metabolito energético é seriamente comprometida. De facto, estas alterações metabólicas progressivas estão ainda associadas a uma diminuição dos parâmetros espermáticos, que seguramente serão responsáveis pelo declínio da saúde reprodutiva masculina.
The survival of the human being lies in a healthy fertility, however, in last decades it has been observed a decline in male fertility. This problem has a particular focus in modern societies, but in the near future will be present in developing countries. External factors associated with lifestyle, such as erroneous eating habits, particularly the excessive intake of high energy diets, have contributed to the increase of metabolic diseases, including obesity and diabetes mellitus (DM). Indeed, the combination of factors such as: changes in the composition of foods, increased consumption of high-energy diets, consumption of foods with high levels of sugar and saturated fats, sedentary lifestyle and the lack of physical activity are the main cause for the increase of this pathology. Obesity and DM are public health problems in developed countries and its incidence has been increasing rapidly among men of reproductive age, contributing to the emergence of subfertility and infertility in these individuals. The metabolic and hormonal dysregulation associated with these pathological stages compromises the male reproductive function, since the hypothalamus-pituitary gonadal axis, also known as reproductive axis, is sensitive to the subtle metabolic disturbances. Testicular tissue consists of a heterogeneous population of somatic and germ cells, where germ cells are dependent on the nutritional support provided by Sertoli cells and any metabolic disorder may alter this metabolic cooperation. Metabolism of testicular cells, in particular of Sertoli cells, present some unique features. Sertoli cells are able to metabolize various substrates (e.g.: glucose, fatty acids, ketone bodies), preferentially metabolizing glucose, being the majority of it converted to lactate and not oxidized via Krebs’ cycle. The mechanisms that regulate the metabolism of Sertoli cells are essential for spermatogenesis and this metabolic process is regulated by several factors, among which insulin and sexual steroid hormones play an important role. Metabolic diseases, such as DM, present in its origin insulin resistance and/or absence, as well as an inability of cells to efficiently respond to insulin stimulation. Given the relevance of this hormone on glucose metabolism and the fact that Sertoli cells express the specific receptors for insulin, we evaluated the metabolic behavior of Sertoli cells under insulin deprivation conditions. In these circumstances, Sertoli cells altered their glycolytic metabolism, decreasing the rate of lactate production through the modulation of the expression of proteins associated with the production and export of lactate. This suggests that Sertoli cells are affected in their metabolic activity under specific pathological conditions associated with insulin deregulation, such is the case of DM. DM induces a generalized endocrine disruption. A direct consequence of DM on testicular function is the inhibition of the synthesis of testosterone (T) and the more severe is the state of DM, the greater the reduction in levels of T. In this work, we showed that the sex steroids, particularly testosterone (and its non aromatizable metabolite 5-dihydrotestosterone) and 17β-estradiol, modulate the glycolytic metabolism of Sertoli cells, favoring the increase of glucose consumption, although the production of lactate is not promoted. In fact, lactate production, which is the primary substrate of developing germ cells, is diminished by the androgenic action. We further studied the effects of T deficiency induced by different stages of DM, pre-diabetes and type 2 diabetes mellitus, in the glycolytic metabolism of Sertoli cells. Our results showed that the more advanced is the state of the disease, the more the glycolytic pathway is compromised. Interestingly, Sertoli cells cultured under T conditions similar to those of type 2 diabetes mellitus stage are able to adopt alternative mechanisms that promote the use of alternative substrates, such as glycogen. At testicular level, it was evidenced that the pre-diabetic state induced by high-energy diets consumption also alters the glycolytic metabolism. Under these conditions, the glycolytic pathway is favored, given the increased expression and activity of essential proteins involved in this metabolic pathway. The expression of proteins associated with the production of lactate is also increased, which may have contributed to the increase in the testicular lactate content. However, and despite the metabolic adaptation observed, the reproductive parameters were affected, which may result from the favoring of a high oxidative environment. In fact, in those conditions, we observed a significant decrease in the expression of proteins involved not only in the maintenance of mitochondrial biogenesis, as in the activation of the reactive oxygen species defense system. The decreased testicular antioxidant potential, as well as the altered mitochondrial respiratory function contributed to a deficient bioenergetic capacity and augmented oxidative environment. In more advanced states of disease, as is the case of type 2 diabetes mellitus, testicular glycolytic metabolism was seriously compromised. Lactate dehydrogenase activity was severely diminished contributing to lower testicular content of lactate. Moreover, in those conditions there seems to be an adaptation of the testicular metabolism, reflected in the content of glycogen in the testes, which was increased. These results implied a testicular metabolic reprogramming under type 2 diabetes mellitus conditions, which promoted alternative metabolic pathways. However, the sperm parameters of the individuals with type 2 diabetes mellitus were seriously compromised, since motility and viability were substancially decreased and the number of sperm with abnormal morphology was increased. In conclusion, this study showed that metabolic diseases, particularly DM, contribute to a decrease in male reproductive potential by promoting profound alterations in testicular cellular metabolism, and particularly in the metabolism of Sertoli cells. Spermatogenesis is a complex process and the glycolytic metabolism is pivotal for the success of this cellular event. Glucose metabolism in Sertoli cells is targeted by numerous regulatory factors and both the initial and the advanced stages of DM the metabolism of glucose is altered in these cells. Furthermore, the more pronounced effects were observed in the most advanced stages of DM. In fact, we observed that, in the prodromal stage of DM, testicular metabolism tends to adapt in order to ensure an adequate production of lactate for developing germ cells. However, in more advanced stages of that disease, lactate production is seriously compromised. Moreover, these metabolic changes were associated with a decline in the reproductive parameters, that may lead to infertility, and that surely will be accountable for the decline in male reproductive health.