Reduction of In Vivo Placental Amino Acid Transport Precedes the Development of Intrauterine Growth Restriction in the Non-Human Primate

Intrauterine growth restriction (IUGR) is associated with reduced placental amino acid transport (AAT). However, it remains to be established if changes in AAT contribute to restricted fetal growth. We hypothesized that reduced in vivo placental AAT precedes the development of IUGR in baboons with maternal nutrient restriction (MNR). Baboons were fed either a control (ad libitum) or MNR diet (70% of control diet) from gestational day (GD) 30. At GD 140, in vivo transplacental AA transport was measured by infusing nine (13)C- or (2)H-labeled essential amino acids (EAAs) as a bolus into the maternal circulation at cesarean section. A fetal vein-to-maternal artery mole percent excess ratio for each EAA was measured. Microvillous plasma membrane (MVM) system A and system L transport activity were determined. Fetal and placental weights were not significantly different between MNR and control. In vivo, the fetal vein-to-maternal artery mole percent excess ratio was significantly decreased for tryptophan in MNR. MVM system A and system L activity was markedly reduced in MNR. Reduction of in vivo placental amino acid transport precedes fetal growth restriction in the non-human primate, suggesting that reduced placental amino acid transfer may contribute to IUGR.

[1]  Lawrence Busch,et al.  Food Security in the United States , 2021 .

[2]  Shogo Matoba,et al.  Paternal knockout of Slc38a4/SNAT4 causes placental hypoplasia associated with intrauterine growth restriction in mice , 2019, Proceedings of the National Academy of Sciences.

[3]  A. Malhotra,et al.  Neonatal Morbidities of Fetal Growth Restriction: Pathophysiology and Impact , 2019, Front. Endocrinol..

[4]  Gang Liu,et al.  The Tryptophan Pathway Targeting Antioxidant Capacity in the Placenta , 2018, Oxidative medicine and cellular longevity.

[5]  S. Weintraub,et al.  Down-Regulation of Placental Transport of Amino Acids Precedes the Development of Intrauterine Growth Restriction in Maternal Nutrient Restricted Baboons , 2016, Biology of reproduction.

[6]  D. Sharma,et al.  Intrauterine growth restriction – part 1 , 2016, The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians.

[7]  Madhulika B. Gupta,et al.  Increased ubiquitination and reduced plasma membrane trafficking of placental amino acid transporter SNAT-2 in human IUGR , 2015, Clinical science.

[8]  M. Nijland,et al.  Reduced placental amino acid transport in response to maternal nutrient restriction in the baboon. , 2015, American journal of physiology. Regulatory, integrative and comparative physiology.

[9]  Y. Kanai,et al.  Expression and functional characterisation of System L amino acid transporters in the human term placenta , 2015, Reproductive Biology and Endocrinology.

[10]  T. Q. Bartlett,et al.  Increased aggressive and affiliative display behavior in intrauterine growth restricted baboons , 2015, Journal of medical primatology.

[11]  D. Darmaun,et al.  Maternal and fetal tryptophan metabolism in gestating rats: effects of intrauterine growth restriction , 2015, Amino Acids.

[12]  Guoyao Wu,et al.  Down‐regulation of placental mTOR, insulin/IGF‐I signaling, and nutrient transporters in response to maternal nutrient restriction in the baboon , 2014, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[13]  I. Cetin,et al.  SNAT2 expression and regulation in human growth-restricted placentas , 2013, Pediatric Research.

[14]  T. Powell,et al.  Placental transport in response to altered maternal nutrition , 2012, Journal of Developmental Origins of Health and Disease.

[15]  Daiana Vianna,et al.  Leucine is essential for attenuating fetal growth restriction caused by a protein-restricted diet in rats. , 2012, The Journal of nutrition.

[16]  G. Burton,et al.  Dietary composition programmes placental phenotype in mice , 2011, The Journal of physiology.

[17]  G. Burton,et al.  Placental-specific Igf2 deficiency alters developmental adaptations to undernutrition in mice. , 2011, Endocrinology.

[18]  Nicole R. Zürcher,et al.  Prenatal betamethasone exposure has sex specific effects in reversal learning and attention in juvenile baboons. , 2011, American journal of obstetrics and gynecology.

[19]  M. Nijland,et al.  Moderate Global Reduction in Maternal Nutrition Has Differential Stage of Gestation Specific Effects on β1- and β2-Adrenergic Receptors in the Fetal Baboon Liver , 2011, Reproductive Sciences.

[20]  Jesse S. Rodriguez,et al.  CANTAB delayed matching to sample task performance in juvenile baboons , 2011, Journal of Neuroscience Methods.

[21]  Mei J. Zhu,et al.  Upregulation of growth signaling and nutrient transporters in cotyledons of early to mid-gestational nutrient restricted ewes. , 2011, Placenta.

[22]  Y. Kanai,et al.  Maternal Protein Restriction in the Rat Inhibits Placental Insulin, mTOR, and STAT3 Signaling and Down-Regulates Placental Amino Acid Transporters , 2011, Endocrinology.

[23]  Thomas J McDonald,et al.  Vulnerability of the fetal primate brain to moderate reduction in maternal global nutrient availability , 2011, Proceedings of the National Academy of Sciences.

[24]  Nicole R. Zürcher,et al.  Performance of juvenile baboons on neuropsychological tests assessing associative learning, motivation and attention , 2010, Journal of Neuroscience Methods.

[25]  M. Nijland,et al.  Epigenetic modification of fetal baboon hepatic phosphoenolpyruvate carboxykinase following exposure to moderately reduced nutrient availability , 2010, The Journal of physiology.

[26]  G. Burton,et al.  Adaptations in placental phenotype support fetal growth during undernutrition of pregnant mice , 2010, The Journal of physiology.

[27]  R. Devlieger,et al.  Sonographic biometrical normograms and estimation of fetal weight in the baboon (Papio anubis) , 2009, Journal of medical primatology.

[28]  F. Battaglia,et al.  The transplacental transport of essential amino acids in uncomplicated human pregnancies. , 2009, American journal of obstetrics and gynecology.

[29]  M. Yliperttula,et al.  Pharmacokinetic role of L-type amino acid transporters LAT1 and LAT2. , 2008, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[30]  J. Roberts,et al.  Placental system A amino acid transport is reduced in pregnancies with small for gestational age (SGA) infants but not in preeclampsia with SGA infants. , 2008, Placenta.

[31]  Kent L Thornburg,et al.  Effect of in Utero and Early-life Conditions on Adult Health and Disease Epidemiol Ogic a Nd Clinic a L Observations , 2022 .

[32]  T. Q. Bartlett,et al.  Metabolic adjustments to moderate maternal nutrient restriction , 2007, British Journal of Nutrition.

[33]  T. Powell,et al.  Mammalian target of rapamycin in the human placenta regulates leucine transport and is down‐regulated in restricted fetal growth , 2007, The Journal of physiology.

[34]  M. Nijland,et al.  Non‐human primate fetal kidney transcriptome analysis indicates mammalian target of rapamycin (mTOR) is a central nutrient‐responsive pathway , 2007, The Journal of physiology.

[35]  V. Ganapathy,et al.  Down‐regulation of placental transport of amino acids precedes the development of intrauterine growth restriction in rats fed a low protein diet , 2006, The Journal of physiology.

[36]  M. Nijland,et al.  Gene expression profile differences in left and right liver lobes from mid‐gestation fetal baboons: a cautionary tale , 2006, The Journal of physiology.

[37]  M. Nijland,et al.  Effect of 30 per cent maternal nutrient restriction from 0.16 to 0.5 gestation on fetal baboon kidney gene expression , 2006, The Journal of physiology.

[38]  Thomas Jansson,et al.  Placental Phenotypes of Intrauterine Growth , 2005, Pediatric Research.

[39]  D. Brodsky,et al.  Current Concepts in Intrauterine Growth Restriction , 2004, Journal of intensive care medicine.

[40]  F. Verrey System L: heteromeric exchangers of large, neutral amino acids involved in directional transport , 2003, Pflügers Archiv.

[41]  T. Powell,et al.  Alterations in the activity of placental amino acid transporters in pregnancies complicated by diabetes. , 2002, Diabetes.

[42]  T. Powell,et al.  Glucose transport and system A activity in syncytiotrophoblast microvillous and basal plasma membranes in intrauterine growth restriction. , 2002, Placenta.

[43]  C. Boyd,et al.  Characterisation of L‐tryptophan transporters in human placenta: a comparison of brush border and basal membrane vesicles , 2001, The Journal of physiology.

[44]  T. Powell,et al.  Placental Transport of Leucine and Lysine Is Reduced in Intrauterine Growth Restriction1 , 1998, Pediatric Research.

[45]  C. Sibley,et al.  Association between the Activity of the System A Amino Acid Transporter in the Microvillous Plasma Membrane of the Human Placenta and Severity of Fetal Compromise in Intrauterine Growth Restriction , 1997, Pediatric Research.

[46]  C. Sibley,et al.  Amino Acid (System A) Transporter Activity in Microvillous Membrane Vesicles from the Placentas of Appropriate and Small for Gestational Age Babies , 1993, Pediatric Research.

[47]  J. Dobbing,et al.  Fetal nutrition and cardiovascular disease in adult life , 1993, The Lancet.

[48]  C Osmond,et al.  Fetal and infant growth and impaired glucose tolerance at age 64. , 1991, BMJ.

[49]  D. Varma,et al.  Effects of protein-calorie malnutrition on transplacental kinetics of aminoisobutyric acid in rats. , 1991, Placenta.

[50]  N. Illsley,et al.  Simultaneous preparation of paired, syncytial, microvillous and basal membranes from human placenta. , 1990, Biochimica et biophysica acta.

[51]  V. Ganapathy,et al.  Characterization of tryptophan transport in human placental brush-border membrane vesicles. , 1986, The Biochemical journal.

[52]  P. Rosso Maternal-fetal exchange during protein malnutrition in the rat. Placental transfer of glucose and a nonmetabolizable glucose analog. , 1977, The Journal of nutrition.

[53]  P. Rosso Maternal-fetal exchange during protein malnutrition in the rat. Placental transfer of alpha-amino isobutyric acid. , 1977, The Journal of nutrition.

[54]  P. Rosso Maternal malnutrition and placental transfer of alpha-aminoisobutyric acid in the rat. , 1975, Science.

[55]  K. A. Vatz,et al.  The use of N-methylation to direct route of mediated transport of amino acids. , 1965, The Journal of biological chemistry.