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Journal articles on the topic 'Placenta; transporter; transportér'

Author: Grafiati

Published: 28 June 2021

Last updated: 29 July 2025

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1

Granitzer, Sebastian, Isabella Ellinger, Rumsha Khan, et al. "In vitro function and in situ localization of Multidrug Resistance-associated Protein (MRP)1 (ABCC1) suggest a protective role against methyl mercury-induced oxidative stress in the human placenta." Archives of Toxicology 94, no. 11 (2020): 3799–817. http://dx.doi.org/10.1007/s00204-020-02900-5.

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Abstract Methyl mercury (MeHg) is an organic highly toxic compound that is transported efficiently via the human placenta. Our previous data suggest that MeHg is taken up into placental cells by amino acid transporters while mercury export from placental cells mainly involves ATP binding cassette (ABC) transporters. We hypothesized that the ABC transporter multidrug resistance-associated protein (MRP)1 (ABCC1) plays an essential role in mercury export from the human placenta. Transwell transport studies with MRP1-overexpressing Madin-Darby Canine Kidney (MDCK)II cells confirmed the function of

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2

Shearman, Lauren P., Alison M. McReynolds, Feng C. Zhou, and Jerrold S. Meyer. "Relationship between [125I]RTI-55-labeled cocaine binding sites and the serotonin transporter in rat placenta." American Journal of Physiology-Cell Physiology 275, no. 6 (1998): C1621—C1629. http://dx.doi.org/10.1152/ajpcell.1998.275.6.c1621.

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We investigated the characteristics of cocainelike binding sites in rat placenta using [125I]RTI-55. [3H]paroxetine binding and immunocytochemical staining for serotonin [5-hydroxytryptamine (5-HT)] and for the 5-HT transporter were also used to obtain evidence for rat placental 5-HT uptake. [125I]RTI-55 saturation analyses with membranes from normal gestational day 20 placentas yielded curvilinear Scatchard plots that were resolved into high- and low-affinity components (mean dissociation constants of 0.29 and 7.9 nM, respectively). Drug competition studies with various monoamine uptake inhib

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3

do Imperio, Guinever Eustaquio, Enrrico Bloise, Mohsen Javam, et al. "Chorioamnionitis Induces a Specific Signature of Placental ABC Transporters Associated with an Increase of miR-331-5p in the Human Preterm Placenta." Cellular Physiology and Biochemistry 45, no. 2 (2018): 591–604. http://dx.doi.org/10.1159/000487100.

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Background/Aims: The ATP-binding cassette (ABC) transporters mediate drug biodisposition and immunological responses in the placental barrier. In vitro infective challenges alter expression of specific placental ABC transporters. We hypothesized that chorioamnionitis induces a distinct pattern of ABC transporter expression. Methods: Gene expression of 50 ABC transporters was assessed using TaqMan® Human ABC Transporter Array, in preterm human placentas without (PTD; n=6) or with histological chorioamnionitis (PTDC; n=6). Validation was performed using qPCR, immunohistochemistry and Western blo

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4

Xu, Jie, Jiao Wang, Yang Cao, et al. "Downregulation of Placental Amino Acid Transporter Expression and mTORC1 Signaling Activity Contributes to Fetal Growth Retardation in Diabetic Rats." International Journal of Molecular Sciences 21, no. 5 (2020): 1849. http://dx.doi.org/10.3390/ijms21051849.

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Alterations in placental transport may contribute to abnormal fetal intrauterine growth in pregnancies complicated by diabetes, but it is not clear whether the placental amino acid transport system is altered in diabetic pregnancies. We therefore studied the changes in the expressions of placental amino acid transporters in a rat model of diabetes induced by streptozotocin, and tested the effects of hyperglycemia on trophoblast amino acid transporter in vitro. Our results showed that the expressions for key isoforms of system L amino acid transporters were significantly reduced in the placenta

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5

Roos, S., Y. Kanai, P. D. Prasad, T. L. Powell, and T. Jansson. "Regulation of placental amino acid transporter activity by mammalian target of rapamycin." American Journal of Physiology-Cell Physiology 296, no. 1 (2009): C142—C150. http://dx.doi.org/10.1152/ajpcell.00330.2008.

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The activity of placental amino acid transporters is decreased in intrauterine growth restriction (IUGR), but the underlying regulatory mechanisms have not been established. Inhibition of the mammalian target of rapamycin (mTOR) signaling pathway has been shown to decrease the activity of the system L amino acid transporter in human placental villous fragments, and placental mTOR activity is decreased in IUGR. In the present study, we used cultured primary trophoblast cells to study mTOR regulation of placental amino acid transporters in more detail and to test the hypothesis that mTOR alters

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6

Cleal, J. K., P. E. Day, C. L. Simner, et al. "Placental amino acid transport may be regulated by maternal vitamin D and vitamin D-binding protein: results from the Southampton Women's Survey." British Journal of Nutrition 113, no. 12 (2015): 1903–10. http://dx.doi.org/10.1017/s0007114515001178.

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Both maternal 25-hydroxyvitamin D (25(OH)D) concentrations during pregnancy and placental amino acid transporter gene expression have been associated with development of the offspring in terms of body composition and bone structure. Several amino acid transporter genes have vitamin D response elements in their promoters suggesting the possible linkage of these two mechanisms. We aimed to establish whether maternal 25(OH)D and vitamin D-binding protein (VDBP) levels relate to expression of placental amino acid transporters. RNA was extracted from 102 placental samples collected in the Southampt

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7

Ericsson, Anette, Bengt Hamark, Nina Jansson, Bengt R. Johansson, Theresa L. Powell, and Thomas Jansson. "Hormonal regulation of glucose and system A amino acid transport in first trimester placental villous fragments." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 288, no. 3 (2005): R656—R662. http://dx.doi.org/10.1152/ajpregu.00407.2004.

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Alterations in placental nutrient transfer have been implicated in fetal growth abnormalities. In pregnancies complicated by diabetes and accelerated fetal growth, upregulations of glucose transporter 1 (GLUT1) and amino acid transporter system A have been shown in the syncytiotrophoblast of term placenta. In contrast, intrauterine growth restriction is associated with a downregulation of placental system A transporters. However, underlying mechanisms of transporter regulation are poorly understood, particularly in early pregnancy. In this study, hormonal regulation of placental glucose and sy

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8

Taggi, Valerio, Mario Riera Romo, Micheline Piquette-Miller, Henriette E. Meyer zu Schwabedissen, and Sibylle Neuhoff. "Transporter Regulation in Critical Protective Barriers: Focus on Brain and Placenta." Pharmaceutics 14, no. 7 (2022): 1376. http://dx.doi.org/10.3390/pharmaceutics14071376.

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Drug transporters play an important role in the maintenance of chemical balance and homeostasis in different tissues. In addition to their physiological functions, they are crucial for the absorption, distribution, and elimination of many clinically important drugs, thereby impacting therapeutic efficacy and toxicity. Increasing evidence has demonstrated that infectious, metabolic, inflammatory, and neurodegenerative diseases alter the expression and function of drug transporters. However, the current knowledge on transporter regulation in critical protective barriers, such as the brain and pl

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Chen, Xin, Zsuzsanna Gáborik, Qingcheng Mao та Jashvant D. Unadkat. "Are Δ9-Tetrahydrocannabinol and Its Major Metabolites Substrates or Inhibitors of Placental or Human Hepatic Drug Solute-Carrier Transporters?" International Journal of Molecular Sciences 25, № 22 (2024): 12036. http://dx.doi.org/10.3390/ijms252212036.

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Δ9-Tetrahydrocannabinol (THC) is the primary psychoactive component of cannabis which is being increasingly consumed by pregnant people. In humans, THC is sequentially metabolized in the liver to its circulating metabolites 11-hydroxy-THC (11-OH-THC, psychoactive) and 11-nor-9-carboxy-THC (THC-COOH, non-psychoactive). Human and macaque data show that fetal exposure to THC is considerably lower than the corresponding maternal exposure. Through perfused human placenta studies, we showed that this is due to the active efflux of THC (fetal-to-maternal) by a placental transporter(s) other than P-gl

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Audette, Melanie C., John R. G. Challis, Rebecca L. Jones, Colin P. Sibley, and Stephen G. Matthews. "Synthetic Glucocorticoid Reduces Human Placental System A Transport in Women Treated With Antenatal Therapy." Journal of Clinical Endocrinology & Metabolism 99, no. 11 (2014): E2226—E2233. http://dx.doi.org/10.1210/jc.2014-2157.

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Context: Synthetic glucocorticoids (sGCs) are routinely given to women with threatened preterm labor and have been linked to fetal growth restriction and developmental programming. Reductions in fetal growth are likely to be mediated by placental dysfunction, including altered nutrient transport. sGCs modify the system A neutral amino acid transporter in vitro, but there are no in vivo comparable data in human placenta. Objective: Because ∼30% of women who receive sGCs carry to term, our objective was to examine the short- and longer-term consequences of antenatal sGCs on placental system A tr

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Han, Lyrialle W., Chunying Gao, Yuchen Zhang, Joanne Wang, and Qingcheng Mao. "Transport of Bupropion and its Metabolites by the Model CHO and HEK293 Cell Lines." Drug Metabolism Letters 13, no. 1 (2019): 25–36. http://dx.doi.org/10.2174/1872312813666181129101507.

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<P>Background: Bupropion (BUP) is widely used as an antidepressant and smoking cessation aid. There are three major pharmacologically active metabolites of BUP, Erythrohydrobupropion (EB), Hydroxybupropion (OHB) and Threohydrobupropion (TB). At present, the mechanisms underlying the overall disposition and systemic clearance of BUP and its metabolites have not been well understood, and the role of transporters has not been studied. </P><P> Objective: The goal of this study was to investigate whether BUP and its active metabolites are substrates of the major hepatic uptake and

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Vinot, C., L. Gavard, J. M. Tréluyer, et al. "Placental Transfer of Maraviroc in anEx VivoHuman Cotyledon Perfusion Model and Influence of ABC Transporter Expression." Antimicrobial Agents and Chemotherapy 57, no. 3 (2013): 1415–20. http://dx.doi.org/10.1128/aac.01821-12.

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ABSTRACTNowadays, antiretroviral therapy is recommended during pregnancy to prevent mother-to-child transmission of HIV. However, for many antiretroviral drugs, including maraviroc, a CCR5 antagonist, very little data exist regarding placental transfer. Besides, various factors may modulate this transfer, including efflux transporters belonging to the ATP-binding cassette (ABC) transporter superfamily. We investigated maraviroc placental transfer and the influence of ABC transporter expression on this transfer using the human cotyledon perfusion model. Term placentas were perfusedex vivofor 90

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Rosario, Fredrick J., Nina Jansson, Yoshikatsu Kanai, Puttur D. Prasad, Theresa L. Powell, and Thomas Jansson. "Maternal Protein Restriction in the Rat Inhibits Placental Insulin, mTOR, and STAT3 Signaling and Down-Regulates Placental Amino Acid Transporters." Endocrinology 152, no. 3 (2011): 1119–29. http://dx.doi.org/10.1210/en.2010-1153.

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The mechanisms underlying reduced fetal growth in response to maternal protein restriction are not well established. Maternal levels of insulin, IGF-I, and leptin are decreased in rats fed a low protein (LP) diet. Because these hormones stimulate placental amino acid transporters in vitro, we hypothesized that maternal protein restriction inhibits placental leptin, insulin/IGF-I, and mammalian target of rapamycin signaling and down-regulates the expression and activity of placental amino acid transporters. Pregnant rats were fed either an isocaloric low protein (LP, 4% protein) or control diet

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Lynch, Cameron, Asghar Ali, Victoria Kennedy, Amelia R. Tanner, Quinton A. Winger, and Russell V. Anthony. "PSII-34 Placental GLUT3 (SLC2A3) RNA interference: Impact on fetal growth at mid-gestation." Journal of Animal Science 98, Supplement_4 (2020): 378. http://dx.doi.org/10.1093/jas/skaa278.665.

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Abstract Glucose is the predominant energy substrate for fetal oxidative processes and growth, and is taken up by the placenta and transported to the fetus by the facilitative transporters GLUT1 (SLC2A1) and GLUT3 (SLC2A3). SLC2A1 is the most abundant placental transporter, and as such is believed to be the primary glucose transporter in human and sheep placenta. However, SLC2A3 exhibits a six-fold greater glucose transport capacity, and in sheep, SLC2A3 is localized to the apical trophoblast membrane, whereas SLC2A1 is predominantly localized to the basolateral membrane, indicating that both

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15

Scott, Hailey, Lilian M. Martinelli, David Grynspan, Enrrico Bloise, and Kristin L. Connor. "Preterm Birth Associates With Increased Placental Expression of MDR Transporters Irrespective of Prepregnancy BMI." Journal of Clinical Endocrinology & Metabolism 107, no. 4 (2021): 1140–58. http://dx.doi.org/10.1210/clinem/dgab813.

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Abstract Context Preterm birth (PTB) and suboptimal prepregnancy body mass index (BMI) operate through inflammatory pathways to impair fetoplacental development. Placental efflux transporters mediate fetal protection and nutrition; however, few studies consider the effect of both PTB and BMI on fetal protection. We hypothesized that PTB would alter the expression of placental multidrug resistance (MDR) transporters and selected proinflammatory cytokines, and that maternal underweight and obesity would further impair placental phenotype. Objective To determine whether placental MDR transporters

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Chang, Yao-Lung, Shuenn-Dyh Chang, An-Shine Chao, Martin Sieber, Chia-Lung Tsai, and Po-Jen Cheng. "Effect of Hypoxia on Glucose Transporter 1 and 3 Gene Expression in Placental Mesenchymal Stem Cells Derived from Growth-Restricted Fetuses." Genes 13, no. 5 (2022): 752. http://dx.doi.org/10.3390/genes13050752.

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(1) Background: Glucose is transferred from maternal blood to the fetus by glucose transporters. What is the effect of hypoxia on the gene expression of placenta glucose transporter 1 (GLUT1) and glucose transporter 3 (GLUT3) in growth-restricted fetus is interesting. (2) Methods: The gene expression of GLUT1 and GLUT3 and the protein expression of HIF-1α were evaluated under nonhypoxic conditions and after 4 and 8 h under hypoxic conditions in placental mesenchymal stem cells derived from monochorionic twin pregnancies with selective intrauterine growth restriction. (3) Results: The gene expr

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Chang, Yao-Lung, Shuenn-Dyh Chang, An-Shine Chao, Martin Sieber, Chia-Lung Tsai, and Po-Jen Cheng. "Effect of Hypoxia on Glucose Transporter 1 and 3 Gene Expression in Placental Mesenchymal Stem Cells Derived from Growth-Restricted Fetuses." Genes 13, no. 5 (2022): 752. http://dx.doi.org/10.3390/genes13050752.

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(1) Background: Glucose is transferred from maternal blood to the fetus by glucose transporters. What is the effect of hypoxia on the gene expression of placenta glucose transporter 1 (GLUT1) and glucose transporter 3 (GLUT3) in growth-restricted fetus is interesting. (2) Methods: The gene expression of GLUT1 and GLUT3 and the protein expression of HIF-1α were evaluated under nonhypoxic conditions and after 4 and 8 h under hypoxic conditions in placental mesenchymal stem cells derived from monochorionic twin pregnancies with selective intrauterine growth restriction. (3) Results: The gene expr

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18

St-Pierre, M. V., T. Stallmach, A. Freimoser Grundschober, et al. "Temporal expression profiles of organic anion transport proteins in placenta and fetal liver of the rat." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 287, no. 6 (2004): R1505—R1516. http://dx.doi.org/10.1152/ajpregu.00279.2003.

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Physiological cholestasis linked to immature hepatobiliary transport systems for organic anions occurs in rat and human neonates. In utero, the placenta facilitates vectorial transfer of certain fetal-derived solutes to the maternal circulation for elimination. We compared the ontogenesis of organic anion transporters in the placenta and the fetal liver of the rat to assess their relative abundance throughout gestation and to determine whether the placenta compensates for the late maturation of transporters in the developing liver. The mRNA of members of the organic anion transporting polypept

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Horackova, Hana, Rona Karahoda, Lukas Cerveny, et al. "Effect of Selected Antidepressants on Placental Homeostasis of Serotonin: Maternal and Fetal Perspectives." Pharmaceutics 13, no. 8 (2021): 1306. http://dx.doi.org/10.3390/pharmaceutics13081306.

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Depression is a prevalent condition affecting up to 20% of pregnant women. Hence, more than 10% are prescribed antidepressant drugs, mainly serotonin reuptake inhibitors (SSRIs) and selective serotonin and noradrenaline reuptake inhibitors (SNRIs). We hypothesize that antidepressants disturb serotonin homeostasis in the fetoplacental unit by inhibiting serotonin transporter (SERT) and organic cation transporter 3 (OCT3) in the maternal- and fetal-facing placental membranes, respectively. Paroxetine, citalopram, fluoxetine, fluvoxamine, sertraline, and venlafaxine were tested in situ (rat term

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Hayward, Christina E., Susan L. Greenwood, Colin P. Sibley, Philip N. Baker, John R. G. Challis, and Rebecca L. Jones. "Effect of maternal age and growth on placental nutrient transport: potential mechanisms for teenagers' predisposition to small-for-gestational-age birth?" American Journal of Physiology-Endocrinology and Metabolism 302, no. 2 (2012): E233—E242. http://dx.doi.org/10.1152/ajpendo.00192.2011.

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Teenagers have an increased risk of delivering small-for-gestational-age (SGA) infants. Young maternal age and continued skeletal growth have been implicated as causal factors. In growing adolescent sheep, impaired placental development and nutrient transfer cause reduced birth weight. In human pregnancies, SGA is associated with reduced placental amino acid transport. Maternal growth has no effect on placental morphology or cell turnover, but growing teenagers have higher birth weight:placental weight ratios than nongrowing teenagers. We hypothesized that placental nutrient transporter activi

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Roos, Sara, Theresa L. Powell, and Thomas Jansson. "Placental mTOR links maternal nutrient availability to fetal growth." Biochemical Society Transactions 37, no. 1 (2009): 295–98. http://dx.doi.org/10.1042/bst0370295.

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The mTOR (mammalian target of rapamycin) signalling pathway functions as a nutrient sensor, both in individual cells and, more globally, in organs such as the fat body in Drosophila and the hypothalamus in the rat. The activity of placental amino acid transporters is decreased in IUGR (intrauterine growth restriction), and recent experimental evidence suggests that these changes contribute directly to the restricted fetal growth. We have shown that mTOR regulates the activity of the placental L-type amino acid transporter system and that placental mTOR activity is decreased in IUGR. The presen

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Stanirowski, Paweł Jan, Dariusz Szukiewicz, Agata Majewska, et al. "Differential Expression of Glucose Transporter Proteins GLUT-1, GLUT-3, GLUT-8 and GLUT-12 in the Placenta of Macrosomic, Small-for-Gestational-Age and Growth-Restricted Foetuses." Journal of Clinical Medicine 10, no. 24 (2021): 5833. http://dx.doi.org/10.3390/jcm10245833.

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Placental transfer of glucose constitutes one of the major determinants of the intrauterine foetal growth. The objective of the present study was to evaluate the expression of glucose transporter proteins GLUT-1, GLUT-3, GLUT-8 and GLUT-12 in the placenta of macrosomic, small-for-gestational-age (SGA) and growth-restricted foetuses (FGR). A total of 70 placental tissue samples were collected from women who delivered macrosomic ≥4000 g (n = 26), SGA (n = 11), growth-restricted (n = 13) and healthy control neonates (n = 20). Computer-assisted quantitative morphometry of stained placental section

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Emoto, Akiko, Fumihiko Ushigome, Noriko Koyabu, et al. "H+-linked transport of salicylic acid, an NSAID, in the human trophoblast cell line BeWo." American Journal of Physiology-Cell Physiology 282, no. 5 (2002): C1064—C1075. http://dx.doi.org/10.1152/ajpcell.00179.2001.

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We investigated the transport of salicylic acid and l-lactic acid across the placenta using the human trophoblast cell line BeWo. We performed uptake experiments and measured the change in intracellular pH (pHi). The uptakes of [14C]salicylic acid andl-[14C]lactic acid were temperature- and extracellular pH-dependent and saturable at higher concentrations. Both uptakes were also reduced by FCCP, nigericin, and NaN3. Various nonsteroidal anti-inflammatory drugs (NSAIDs) strongly inhibited the uptake of l-[14C]lactic acid. Salicylic acid and ibuprofen noncompetitively inhibited the uptake ofl-[1

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Powell, Theresa L., Kenneth Barentsen, Owen Vaughan, et al. "Knockdown of Placental Major Facilitator Superfamily Domain Containing 2a in Pregnant Mice Reduces Fetal Brain Growth and Phospholipid Docosahexaenoic Acid Content." Nutrients 15, no. 23 (2023): 4956. http://dx.doi.org/10.3390/nu15234956.

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Introduction: Docosahexaenoic acid (DHA) is an n-3 long chain polyunsaturated fatty acid critical for fetal brain development that is transported to the fetus from the mother by the placenta. The lysophosphatidylcholine (LPC) transporter, Major Facilitator Superfamily Domain Containing 2a (MFSD2a), is localized in the basal plasma membrane of the syncytiotrophoblast of the human placenta, and MFSD2a expression correlates with umbilical cord blood LPC-DHA levels in human pregnancy. We hypothesized that placenta-specific knockdown of MFSD2a in pregnant mice reduces phospholipid DHA accumulation

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Bzoskie, L., L. Blount, K. Kashiwai, Y. T. Tseng, W. W. Hay, and J. F. Padbury. "Placental norepinephrine clearance: in vivo measurement and physiological role." American Journal of Physiology-Endocrinology and Metabolism 269, no. 1 (1995): E145—E149. http://dx.doi.org/10.1152/ajpendo.1995.269.1.e145.

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The intrauterine clearance rate of catecholamines is higher than in newborn animals or in adults. The separate contributions of the fetus and placenta to this clearance are not known. The placenta is a site of expression of the amine plasma membrane transporters that mediate this process. To determine the physiological role of this placental transporter in vivo, we studied fetal sheep at 123 days with common umbilical vein (UV), fetal arterial (AO), and venous catheters. Tritiated norepinephrine ([3H]NE) was infused to determine the kinetics of placental and fetal NE appearance and clearance r

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Lofthouse, E. M., S. Perazzolo, S. Brooks, et al. "Phenylalanine transfer across the isolated perfused human placenta: an experimental and modeling investigation." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 310, no. 9 (2016): R828—R836. http://dx.doi.org/10.1152/ajpregu.00405.2015.

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Membrane transporters are considered essential for placental amino acid transfer, but the contribution of other factors, such as blood flow and metabolism, is poorly defined. In this study we combine experimental and modeling approaches to understand the determinants of [14C]phenylalanine transfer across the isolated perfused human placenta. Transfer of [14C]phenylalanine across the isolated perfused human placenta was determined at different maternal and fetal flow rates. Maternal flow rate was set at 10, 14, and 18 ml/min for 1 h each. At each maternal flow rate, fetal flow rates were set at

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Vaughan, Owen R., Fredrick Thompson, Ramón A. Lorca, et al. "Effect of high altitude on human placental amino acid transport." Journal of Applied Physiology 128, no. 1 (2020): 127–33. http://dx.doi.org/10.1152/japplphysiol.00691.2019.

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Women residing at high altitudes deliver infants of lower birth weight than at sea level. Birth weight correlates with placental system A-mediated amino acid transport capacity, and severe environmental hypoxia reduces system A activity in isolated trophoblast and the mouse placenta. However, the effect of high altitude on human placental amino acid transport remains unknown. We hypothesized that microvillous membrane (MVM) system A and system L amino acid transporter activity is lower in placentas of women living at high altitude compared with low-altitude controls. Placentas were collected a

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Ford, Dianne. "Intestinal and placental zinc transport pathways." Proceedings of the Nutrition Society 63, no. 1 (2004): 21–29. http://dx.doi.org/10.1079/pns2003320.

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Mammalian members of the cation diffusion facilitator (CDF) and zrt-, irt-like protein (ZIP) families of Zn transporters, initially identified in Saccharomyces cerevisiae and Arabidopsis thalania spp., have been cloned during the last 8 years and have been classified as families SLC30 and SLC39 respectively. The cloning of human Zn transporters ZnT-like transporter 1 (hZTL1)/ZnT5 (SLC30A5) and hZIP4 (SLC39A4) were major advances in the understanding of the molecular mechanisms of dietary Zn absorption. Both transporters are localised at the enterocyte apical membrane and are, therefore, potent

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McColl, Eliza R., Jeffrey T. Henderson, and Micheline Piquette-Miller. "Dysregulation of Amino Acid Transporters in a Rat Model of TLR7-Mediated Maternal Immune Activation." Pharmaceutics 15, no. 7 (2023): 1857. http://dx.doi.org/10.3390/pharmaceutics15071857.

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Maternal immune activation (MIA) during pregnancy is linked to neurodevelopmental disorders in humans. Similarly, the TLR7 agonist imiquimod alters neurodevelopment in rodents. While the mechanisms underlying MIA-mediated neurodevelopmental changes are unknown, they could involve dysregulation of amino acid transporters essential for neurodevelopment. Therefore, we sought to determine the nature of such transporter changes in both imiquimod-treated rats and human placentas during infection. Pregnant rats received imiquimod on gestational day (GD)14. Transporter expression was measured in place

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Selvaratnam, Johanna, Haiyan Guan, James Koropatnick, and Kaiping Yang. "Metallothionein-I- and -II-deficient mice display increased susceptibility to cadmium-induced fetal growth restriction." American Journal of Physiology-Endocrinology and Metabolism 305, no. 6 (2013): E727—E735. http://dx.doi.org/10.1152/ajpendo.00157.2013.

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Maternal cadmium exposure induces fetal growth restriction (FGR), but the underlying mechanisms remain largely unknown. The placenta is the main organ known to protect the fetus from environmental toxins such as cadmium. In this study, we examine the role of the two key placental factors in cadmium-induced FGR. The first is placental enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which is known to protect the fetus from exposure to high cortisol levels and subsequently FGR, and the second the cadmium binding/sequestering proteins metallotheionein (MT)-I and -II. Using the MT-I/II −

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Bloise, Enrrico, Jair R. S. Braga, Cherley B. V. Andrade, et al. "Altered Umbilical Cord Blood Nutrient Levels, Placental Cell Turnover and Transporter Expression in Human Term Pregnancies Conceived by Intracytoplasmic Sperm Injection (ICSI)." Nutrients 13, no. 8 (2021): 2587. http://dx.doi.org/10.3390/nu13082587.

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Assisted reproductive technologies (ART) may increase risk for abnormal placental development, preterm delivery and low birthweight. We investigated placental morphology, transporter expression and paired maternal/umbilical fasting blood nutrient levels in human term pregnancies conceived naturally (n = 10) or by intracytoplasmic sperm injection (ICSI; n = 11). Maternal and umbilical vein blood from singleton term (>37 weeks) C-section pregnancies were assessed for levels of free amino acids, glucose, free fatty acids (FFA), cholesterol, high density lipoprotein (HDL), low density lipoprote

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Zhou, Fanfan, Mei Hong, and Guofeng You. "Regulation of human organic anion transporter 4 by progesterone and protein kinase C in human placental BeWo cells." American Journal of Physiology-Endocrinology and Metabolism 293, no. 1 (2007): E57—E61. http://dx.doi.org/10.1152/ajpendo.00696.2006.

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Human organic anion transporter 4 (hOAT4) belongs to a family of organic anion transporters that play critical roles in the body disposition of clinically important drugs, including anti-human immunodeficiency virus therapeutics, anti-tumor drugs, antibiotics, antihypertensives, and anti-inflammatories. hOAT4 is abundantly expressed in the placenta. In the current study, we examined the regulation of hOAT4 by pregnancy-specific hormones progesterone (P4) and 17β-estradiol (E2) and by protein kinase C (PKC) in human placental BeWo cells. P4 induced a time- and concentration-dependent downregula

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Shahnawaz, Saira, Usman Shah Nawaz, Jonas Zaugg, et al. "Dysregulated Autophagy Leads to Oxidative Stress and Aberrant Expression of ABC Transporters in Women with Early Miscarriage." Antioxidants 10, no. 11 (2021): 1742. http://dx.doi.org/10.3390/antiox10111742.

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Early miscarriage (EMC) is a devastating obstetrical complication. ATP-binding cassette (ABC) transporters mediate cholesterol transfer across the placenta and enhance cell survival by effluxing substrates from target cells in the presence of stressors. Recent evidence reports an intricate interplay between autophagy and ABC transporters. We hypothesized that dysregulated autophagy and oxidative stress (OS) in the placenta leads to abnormal expression of membrane transporters contributing to poor pregnancy survival in EMC. We determined mRNA and protein expression of autophagy genes (Beclin-1/

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Li, Heng, Etsuko Wada, and Keiji Wada. "Maternal Administration of the Herbal Medicine Toki-Shakuyaku-San Promotes Fetal Growth and Placental Gene Expression in Normal Mice." American Journal of Chinese Medicine 41, no. 03 (2013): 515–29. http://dx.doi.org/10.1142/s0192415x13500377.

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Toki-shakuyaku-san (TSS), an herbal formula based on traditional Chinese medicine, is commonly used in obstetrics. To examine the effects of TSS on the normal mouse fetus and placenta, TSS was administered to normal pregnant mice and their placentas and fetuses were studied. First, the effects of maternal TSS treatment on implantation were investigated. Administration of TSS from gestation day 0.5 (G0.5) to G6.5 showed that litter size was not altered at embryonic day 11.5 (E11.5), but the number of resorbed fetuses was slightly decreased. Then, to investigate effects on fetal and placental gr

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Dai, Wanying, and Micheline Piquette-Miller. "Altered Expression of BCRP Impacts Fetal Accumulation of Rosuvastatin in a Rat Model of Preeclampsia." Pharmaceutics 16, no. 7 (2024): 884. http://dx.doi.org/10.3390/pharmaceutics16070884.

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Expression of the breast cancer resistance protein (BCRP/ABCG2) transporter is downregulated in placentas from women with preeclampsia (PE) and in an immunological rat model of PE. While many drugs are substrates of this important efflux transporter, the impact of PE associated BCRP downregulation on maternal and fetal drug exposure has not been investigated. Using the PE rat model, we performed a pharmacokinetic study with rosuvastatin (RSV), a BCRP substrate, to investigate this impact. PE was induced in rats during gestational days (GD) 13 to 16 with daily low-dose endotoxin. On GD18, RSV (

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Ceckova, Martina, Josef Reznicek, Zuzana Ptackova, et al. "Role of ABC and Solute Carrier Transporters in the Placental Transport of Lamivudine." Antimicrobial Agents and Chemotherapy 60, no. 9 (2016): 5563–72. http://dx.doi.org/10.1128/aac.00648-16.

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ABSTRACTLamivudine is one of the antiretroviral drugs of choice for the prevention of mother-to-child transmission (MTCT) in HIV-positive women. In this study, we investigated the relevance of drug efflux transporters P-glycoprotein (P-gp) (MDR1 [ABCB1]), BCRP (ABCG2), MRP2 (ABCC2), and MATE1 (SLC47A1) for the transmembrane transport and transplacental transfer of lamivudine. We employedin vitroaccumulation and transport experiments on MDCK cells overexpressing drug efflux transporters,in situ-perfused rat term placenta, and vesicular uptake in microvillous plasma membrane (MVM) vesicles isola

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Jones, H. N., T. Jansson, and T. L. Powell. "IL-6 stimulates system A amino acid transporter activity in trophoblast cells through STAT3 and increased expression of SNAT2." American Journal of Physiology-Cell Physiology 297, no. 5 (2009): C1228—C1235. http://dx.doi.org/10.1152/ajpcell.00195.2009.

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Changes in placental nutrient transport are closely associated with abnormal fetal growth. However, the molecular mechanisms underlying the regulation of placental amino acid transporters are unknown. We demonstrate that physiological concentrations of the proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α stimulate the activity of amino acid transporter system A, but not system L, in cultured human primary trophoblast cells. Both cytokines increased the gene and protein expression of the Na+-coupled neutral amino acid transporter (SNAT)2 isoform and upregulated SNA

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Kadife, Elif, Alesia Harper, Natasha De Alwis, Keegan Chien, Natalie Hannan, and Fiona C. Brownfoot. "SLC38A4 Amino Acid Transporter Expression Is Significantly Lower in Early Preterm Intrauterine Growth Restriction Complicated Placentas." International Journal of Molecular Sciences 24, no. 1 (2022): 403. http://dx.doi.org/10.3390/ijms24010403.

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Intrauterine growth restriction (IUGR), predominantly caused by placental insufficiency, affects partitioning of nutrients to the fetus. The system A sodium-coupled transporters (SNAT or SLC38), of types A1, A2, and A4, control non-essential amino acid uptake and supply. Here, we aimed to investigate the expression of these transporters across different placental disease cohorts and cells. To determine disease impact, transporter expressions at the gene (qPCR) and protein (western blots) level were assessed in gestationally matched placental tissues. Early (<34 weeks), and late (34–36 weeks

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Riera-Romo, Mario, Eliza R. McColl, and Micheline Piquette-Miller. "Linking TLR-7 Signaling to Downregulation of Placental P-Glycoprotein: Implications for Fetal Drug Exposure." Pharmaceutics 17, no. 6 (2025): 741. https://doi.org/10.3390/pharmaceutics17060741.

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Background/Objectives: Activation of the Toll-like receptor 7 (TLR-7) plays an important role in the pathogenesis of many autoimmune diseases and viral infections. Although we have previously observed inflammation-mediated dysregulation of placental transporters, the role of TLR-7 has not been examined. Using the TLR-7 agonist, imiquimod (IMQ), we evaluated transporter expression in IMQ-treated pregnant rats and ex vivo in cultured rat placental explants. Methods: We administered 5 mg/kg (IP) of IMQ to pregnant Sprague Dawley rats on gestational day (GD) 14. The expression levels of inflammato

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Osses, N., L. Sobrevia, C. Cordova, SM Jarvis, and DL Yudilevich. "Transport and metabolism of adenosine in diabetic human placenta." Reproduction, Fertility and Development 7, no. 6 (1995): 1499. http://dx.doi.org/10.1071/rd9951499.

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Pregnancy complicated by diabetes is a relatively frequent event and may result in fetal embriopathy. However, little is known regarding whether placental transport functions are altered. In this study, we have compared the activity of the nitrobenzylthioinosine (NBMPR)-sensitive adenosine transporter and adenosine metabolism in human placental brush-border- and basal-membrane vesicles from placentas of normal and diabetic pregnancies. Neither [3H]NBMPR binding, a marker of the facilitative-diffusion nucleoside transporter in the human placenta, nor adenosine metabolism exhibited a significant

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Gong, Christine, Lynn N. Bertagnolli, David W. Boulton, and Paola Coppola. "A Literature Review of Changes in Phase II Drug-Metabolizing Enzyme and Drug Transporter Expression during Pregnancy." Pharmaceutics 15, no. 11 (2023): 2624. http://dx.doi.org/10.3390/pharmaceutics15112624.

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The purpose of this literature review is to comprehensively summarize changes in the expression of phase II drug-metabolizing enzymes and drug transporters in both the pregnant woman and the placenta. Using PubMed®, a systematic search was conducted to identify literature relevant to drug metabolism and transport in pregnancy. PubMed was searched with pre-specified terms during the period of 26 May 2023 to 10 July 2023. The final dataset of 142 manuscripts was evaluated for evidence regarding the effect of gestational age and hormonal regulation on the expression of phase II enzymes (n = 16) a

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Matoba, Shogo, Shoko Nakamuta, Kento Miura, et al. "Paternal knockout of Slc38a4/SNAT4 causes placental hypoplasia associated with intrauterine growth restriction in mice." Proceedings of the National Academy of Sciences 116, no. 42 (2019): 21047–53. http://dx.doi.org/10.1073/pnas.1907884116.

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The placenta is critical in mammalian embryonic development because the embryo’s supply of nutrients, including amino acids, depends solely on mother-to-embryo transport through it. However, the molecular mechanisms underlying this amino acid supply are poorly understood. In this study, we focused on system A amino acid transporters Slc38a1/SNAT1, Slc38a2/SNAT2, and Slc38a4/SNAT4, which carry neutral, short-side-chain amino acids, to determine their involvement in placental or embryonic development. A triple-target CRISPR screen identified Slc38a4/SNAT4 as the critical amino acid transporter f

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Aldahmash, Waleed, Abdel Halim Harrath, Khaldoon Aljerian, Yasser Sabr, and Saleh Alwasel. "Expression of Glucose Transporters 1 and 3 in the Placenta of Pregnant Women with Gestational Diabetes Mellitus." Life 13, no. 4 (2023): 993. http://dx.doi.org/10.3390/life13040993.

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Background: The annual prevalence of gestational diabetes mellitus—characterized by an increase in blood glucose in pregnant women—has been increasing worldwide. The goal of this study was to evaluate the expression of glucose transporter 1 (GLUT1) and glucose transporter 3 (GLUT3) in the placenta of women with gestational diabetes mellitus. Methods: Sixty-five placentas from women admitted to the King Saud University Medical City, Riyadh, Saudi Arabia, were analyzed; 34 and 31 placentas were from healthy pregnant women and women with gestational diabetes, respectively. The expressions of GLUT

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Vogtmann, Rebekka, Alina Riedel, Ivanka Sassmannshausen, et al. "Overexpression of Human sFLT1 in the Spongiotrophoblast Is Sufficient to Induce Placental Dysfunction and Fetal Growth Restriction in Transgenic Mice." International Journal of Molecular Sciences 25, no. 4 (2024): 2040. http://dx.doi.org/10.3390/ijms25042040.

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Preeclampsia (PE) is characterized by maternal hypertension and placental dysfunction, often leading to fetal growth restriction (FGR). It is associated with an overexpression of the anti-angiogenic sFLT1 protein, which originates from the placenta and serves as a clinical biomarker to predict PE. To analyze the impact of sFLT1 on placental function and fetal growth, we generated transgenic mice with placenta-specific human sFLT1 (hsFLT1) overexpression. Immunohistochemical, morphometrical, and molecular analyses of the placentas on 14.5 dpc and 18.5 dpc were performed with a focus on angiogen

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Zaugg, Jonas, Jonai Pujol Giménez, Romina Silvia Cabra, Wilhelm Hofstetter, Matthias A. Hediger, and Christiane Albrecht. "New Insights into the Physiology of Iron Transport: An Interdisciplinary Approach." CHIMIA 76, no. 12 (2022): 996. http://dx.doi.org/10.2533/chimia.2022.996.

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The TransCure project entitled 'Iron Transporters DMT1 and FPN1' took an interdisciplinary approach combining structural biology, chemistry and physiology to gain new insights into iron transport. Proteins studied included Divalent Metal Transporter 1 (DMT1, SLC11A2), enabling the import of Fe2+ into the cytoplasm, and the iron efflux transporter Ferroportin (FPN1, SLC40A1). The physiology and pathophysiology, and the mechanisms underlying iron transport in the gut, across the placenta and in bone were investigated. Small molecule high-throughput screening was used to identify improved modulat

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Wibawa, Aria, Noroyono Wibowo, Ina Susianti Timan, Rinawati Rohsiswatmo, and Atikah Sayogo Putri. "Placental nutrient and transport system in fetus with small for gestational age and growth restriction compared to appropriate for gestational age." Medical Journal of Indonesia 33, no. 3 (2024): 173–83. https://doi.org/10.13181/mji.oa.247361.

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BACKGROUND Fetal growth restriction (FGR) has multifactorial etiology, including nutrition. Fetal nutrient status depends not only on an adequate supply of key nutrients but also optimal delivery, served by the placenta as a major metabolic and transport organ. This study aimed to evaluate the status of placental oxygen and nutrient concentration and their transporters between appropriate for gestational age (AGA), small for gestational age (SGA), and FGR. METHODS This cross-sectional study was conducted at Cipto Mangunkusumo Hospital, Jakarta, from July 2018 to December 2020. Patients were di

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Langmann, Thomas, Richard Mauerer, Alexandra Zahn, et al. "Real-Time Reverse Transcription-PCR Expression Profiling of the Complete Human ATP-Binding Cassette Transporter Superfamily in Various Tissues." Clinical Chemistry 49, no. 2 (2003): 230–38. http://dx.doi.org/10.1373/49.2.230.

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Abstract Background: ATP-binding cassette (ABC) transporters are involved in many physiologic processes, such as lipid transport, sterol homeostasis, immune mechanisms, and drug transport, and cause various human inherited diseases. Thus, the analysis of ABC transporter mRNA expression profiles for basic research, especially in the field of lipid metabolism, for clinical diagnosis, and for monitoring of drug effects is of great interest. Methods: We have developed a rapid, accurate, and highly sensitive real-time reverse transcription-PCR (RT-PCR) method for detection and quantification of all

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Johnson, Gregory A., Avery C. Kramer, Chelsie Steinhauser, et al. "410 Steroids Regulate SLC2A1 and SLC2A3 to Deliver Glucose into Trophectoderm for Metabolism via Glycolysis." Journal of Animal Science 98, Supplement_4 (2020): 188–89. http://dx.doi.org/10.1093/jas/skaa278.348.

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Abstract The conceptuses (embryo/fetus and placental membranes) of pigs require energy to support elongation and implantation, and amounts of glucose and fructose increase in the uterine lumen during the peri-implantation period. Conceptuses from Day 16 of pregnancy were incubated with either 14C-glucose or 14C-fructose and amounts of radiolabeled CO2 released from the conceptuses measured to determine rates of oxidation of glucose and fructose. Both glucose and fructose transport into conceptuses, and glucose is preferentially metabolized in the presence of fructose, while fructose is activel

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Jansson, Thomas, Marisol Castillo-Castrejon, Madhulika B. Gupta, Theresa L. Powell, and Fredrick J. Rosario. "Down-regulation of placental Cdc42 and Rac1 links mTORC2 inhibition to decreased trophoblast amino acid transport in human intrauterine growth restriction." Clinical Science 134, no. 1 (2020): 53–70. http://dx.doi.org/10.1042/cs20190794.

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Abstract Intrauterine growth restriction (IUGR) increases the risk for perinatal complications and metabolic and cardiovascular disease later in life. The syncytiotrophoblast (ST) is the transporting epithelium of the human placenta, and decreased expression of amino acid transporter isoforms in the ST plasma membranes is believed to contribute to IUGR. Placental mechanistic target of rapamycin Complex 2 (mTORC2) signaling is inhibited in IUGR and regulates the trafficking of key amino acid transporter (AAT) isoforms to the ST plasma membrane; however, the molecular mechanisms are unknown. Cdc

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Ruis, Matthew T., Kylie D. Rock, Samantha M. Hall, Brian Horman, Heather B. Patisaul, and Heather M. Stapleton. "PBDEs Concentrate in the Fetal Portion of the Placenta: Implications for Thyroid Hormone Dysregulation." Endocrinology 160, no. 11 (2019): 2748–58. http://dx.doi.org/10.1210/en.2019-00463.

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Abstract During pregnancy, the supply of thyroid hormone (TH) to the fetus is critically important for fetal growth, neural development, metabolism, and maintenance of pregnancy. Additionally, in cases where maternal and placental TH regulation is significantly altered, there is an increased risk of several adverse pregnancy outcomes. It is unclear what may be disrupting placental TH regulation; however, studies suggest that environmental contaminants, such as polybrominated diphenyl ethers (PBDEs), could be playing a role. In this study, Wistar rats were gestationally exposed to a mixture of

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