title: Reduced placental amino acid transport in response to maternal nutrient restriction in the baboon.
abstract: 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.
authors.affiliation: 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.
authors.forename: Priyadarshini
authors.initials: P
authors.lastname: Pantham
authors.affiliation: 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.
authors.forename: Fredrick J
authors.initials: FJ
authors.lastname: Rosario
authors.affiliation: Center for Pregnancy and Newborn Research, Department of Obstetrics and Gynecology, University of Texas Health Science Center, San Antonio, Texas; and.
authors.forename: Mark
authors.initials: M
authors.lastname: Nijland
authors.affiliation: Perinatal Research Center, Department of Pediatrics, Section of Neonatology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado;
authors.forename: Alex
authors.initials: A
authors.lastname: Cheung
authors.affiliation: Center for Pregnancy and Newborn Research, Department of Obstetrics and Gynecology, University of Texas Health Science Center, San Antonio, Texas; and.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Nathanielsz
authors.affiliation: 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.
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Powell
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Henry L
authors.initials: HL
authors.lastname: Galan
authors.affiliation: Center for Pregnancy and Newborn Research, Department of Obstetrics and Gynecology, University of Texas Health Science Center, San Antonio, Texas; and.
authors.forename: Cun
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Thomas
authors.initials: T
authors.lastname: Jansson
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D031204:Caloric Restriction; D018846:Excitatory Amino Acids / Q000378:metabolism; D005260:Female; D005317:Fetal Growth Retardation / Q000503:physiopathology; D020567:Fetal Weight; D008431:Maternal-Fetal Exchange; D009929:Organ Size; D010215:Papio / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D022161:Transport Vesicles; D014327:Trophoblasts / Q000378:metabolism
chemical_list: D000596:Amino Acids; D018846:Excitatory Amino Acids
keywords: fetal growth restriction; maternal-fetal exchange; nonhuman primate