PMID- 26246504 OWN - NLM STAT- MEDLINE DCOM- 20160104 LR - 20210514 IS - 1522-1490 (Electronic) IS - 0363-6119 (Print) IS - 0363-6119 (Linking) VI - 309 IP - 7 DP - 2015 Oct TI - Reduced placental amino acid transport in response to maternal nutrient restriction in the baboon. PG - R740-6 LID - 10.1152/ajpregu.00161.2015 [doi] AB - Intrauterine growth restriction increases the risk of perinatal complications and predisposes the infant to diabetes and cardiovascular disease in later life. Mechanisms by which maternal nutrient restriction (MNR) reduces fetal growth are poorly understood. We hypothesized that MNR decreases placental amino acid (AA) transporter activity, leading to reduced transplacental transfer of AAs. Pregnant baboons were fed either a control (ad libitum, n = 7), or MNR diet (70% of control diet, n = 7) from gestational day (GD) 30. At GD 165 (0.9 gestation), placentas (n = 7 in each group) were collected, and microvillous plasma membrane vesicles (MVM) isolated. MVM system A and system L AA transport was determined in vitro using radiolabeled substrates and rapid filtration techniques. In vivo transplacental AA transport was assessed by infusing nine (13)C- or (2)H-labeled essential AA as a bolus into the maternal circulation (n = 5 control, n = 4 MNR) at cesarean section. A fetal vein-to-maternal artery mole percent excess ratio for each essential AA was calculated. Fetal and placental weights were significantly reduced in the MNR group compared with controls (P < 0.01). The activity of system A and system L was markedly reduced by 73 and 84%, respectively, in MVM isolated from baboon placentas at GD 165 following MNR (P < 0.01). In vivo, the fetal vein-to-maternal artery mole percent excess ratio was significantly reduced for leucine, isoleucine, methionine, phenylalanine, threonine, and tryptophan in MNR baboons (P < 0.05). This is the first study to investigate placental AA transport in a nonhuman primate model of MNR. We demonstrate that the downregulation of system A and system L activity in syncytiotrophoblast MVM in MNR leads to decreased transplacental AA transport and, consequently, reduced circulating fetal AA concentrations, a potential mechanism linking maternal undernutrition to reduced fetal growth. CI - Copyright (c) 2015 the American Physiological Society. FAU - Pantham, Priyadarshini AU - Pantham P AD - Perinatal Research Center, Department of Pediatrics, Section of Neonatology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado; Department of Obstetrics and Gynecology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado priyadarshini.pantham@ucdenver.edu. FAU - Rosario, Fredrick J AU - Rosario FJ AD - Center for Pregnancy and Newborn Research, Department of Obstetrics and Gynecology, University of Texas Health Science Center, San Antonio, Texas; and Department of Obstetrics and Gynecology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado. FAU - Nijland, Mark AU - Nijland M AD - Center for Pregnancy and Newborn Research, Department of Obstetrics and Gynecology, University of Texas Health Science Center, San Antonio, Texas; and. FAU - Cheung, Alex AU - Cheung A AD - Perinatal Research Center, Department of Pediatrics, Section of Neonatology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado; FAU - Nathanielsz, Peter W AU - Nathanielsz PW AD - Center for Pregnancy and Newborn Research, Department of Obstetrics and Gynecology, University of Texas Health Science Center, San Antonio, Texas; and. FAU - Powell, Theresa L AU - Powell TL AD - Perinatal Research Center, Department of Pediatrics, Section of Neonatology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado; Department of Obstetrics and Gynecology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado. FAU - Galan, Henry L AU - Galan HL AD - Department of Obstetrics and Gynecology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado. FAU - Li, Cun AU - Li C AD - Center for Pregnancy and Newborn Research, Department of Obstetrics and Gynecology, University of Texas Health Science Center, San Antonio, Texas; and. FAU - Jansson, Thomas AU - Jansson T AD - Department of Obstetrics and Gynecology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado. LA - eng GR - P01 HD021350/HD/NICHD NIH HHS/United States GR - P01-HD-21350/HD/NICHD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20150805 PL - United States TA - Am J Physiol Regul Integr Comp Physiol JT - American journal of physiology. Regulatory, integrative and comparative physiology JID - 100901230 RN - 0 (Amino Acids) RN - 0 (Excitatory Amino Acids) SB - IM MH - Amino Acids/*metabolism MH - Animals MH - Biological Transport, Active/physiology MH - *Caloric Restriction MH - Excitatory Amino Acids/metabolism MH - Female MH - Fetal Growth Retardation/physiopathology MH - Fetal Weight MH - Maternal-Fetal Exchange MH - Organ Size MH - Papio/*metabolism MH - Placenta/*metabolism MH - Pregnancy MH - Transport Vesicles MH - Trophoblasts/metabolism PMC - PMC4666932 OTO - NOTNLM OT - fetal growth restriction OT - maternal-fetal exchange OT - nonhuman primate EDAT- 2015/08/08 06:00 MHDA- 2016/01/05 06:00 PMCR- 2016/10/01 CRDT- 2015/08/07 06:00 PHST- 2015/04/20 00:00 [received] PHST- 2015/07/30 00:00 [accepted] PHST- 2015/08/07 06:00 [entrez] PHST- 2015/08/08 06:00 [pubmed] PHST- 2016/01/05 06:00 [medline] PHST- 2016/10/01 00:00 [pmc-release] AID - ajpregu.00161.2015 [pii] AID - R-00161-2015 [pii] AID - 10.1152/ajpregu.00161.2015 [doi] PST - ppublish SO - Am J Physiol Regul Integr Comp Physiol. 2015 Oct;309(7):R740-6. doi: 10.1152/ajpregu.00161.2015. Epub 2015 Aug 5.