title: Fetoplacental transport and utilization of amino acids in IUGR--a review.
abstract: Amino acids have multiple functions in fetoplacental development. The supply of amino acids to the fetus involves active transport across and metabolism within the trophoblast. Transport occurs through various amino acid transport systems located on both the maternal and fetal facing membranes, many of which have now been documented to be present in rat, sheep and human placentas. The capacity of the placenta to supply amino acids to the fetus develops during pregnancy through alterations in such factors as surface area and specific time-dependent transport system expression. In intrauterine growth restriction (IUGR), placental surface area and amino acid uptakes are decreased in human and experimental animal models. In an ovine model of IUGR, produced by hyperthermia-induced placental insufficiency (PI-IUGR), umbilical oxygen and essential amino acid uptake rates are significantly reduced in the most severe cases in concert with decreased fetal growth. These changes indicate that severe IUGR is likely associated with a shift in amino acid transport capacity and metabolic pathways within the fetoplacental unit. After transport across the trophoblast in normal conditions, amino acids are actively incorporated into tissue proteins or oxidized. In the sheep IUGR fetus, however, which is hypoxic, hypoglycemic and hypoinsulinemic, there appear to be net effluxes of amino acids from the liver and skeletal muscle, suggesting changes in amino acid metabolism. Potential changes may be occurring in the insulin/IGF-I signaling pathway that includes decreased production and/or activation of specific signaling proteins leading to a reduced protein synthesis in fetal tissues. Such observations in the placental insufficiency model of IUGR indicate that the combination of decreased fetoplacental amino acid uptake and disrupted insulin/IGF signaling in liver and muscle account for decreased fetal growth in IUGR.
authors.affiliation: Perinatal Research Center, Department of Pediatrics, Division of Perinatal Medicine, University of Colorado Health Sciences Center, F441, Aurora, CO 80045, USA. tim.regnault@uchsc.edu
authors.forename: T R H
authors.initials: TR
authors.lastname: Regnault
authors.forename: J E
authors.initials: JE
authors.lastname: Friedman
authors.forename: R B
authors.initials: RB
authors.lastname: Wilkening
authors.forename: R V
authors.initials: RV
authors.lastname: Anthony
authors.forename: W W
authors.initials: WW
authors.lastname: Hay
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active; D004195:Disease Models, Animal; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism*; D005333:Fetus / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008099:Liver / Q000196:embryology / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000196:embryology / Q000378:metabolism; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D015398:Signal Transduction
chemical_list: D000596:Amino Acids; D007328:Insulin; D007334:Insulin-Like Growth Factor I