title: Down-regulation of placental mTOR, insulin/IGF-I signaling, and nutrient transporters in response to maternal nutrient restriction in the baboon.
abstract: The mechanisms by which maternal nutrient restriction (MNR) causes reduced fetal growth are poorly understood. We hypothesized that MNR inhibits placental mechanistic target of rapamycin (mTOR) and insulin/IGF-I signaling, down-regulates placental nutrient transporters, and decreases fetal amino acid levels. Pregnant baboons were fed control (ad libitum, n=11) or an MNR diet (70% of controls, n=11) from gestational day (GD) 30. Placenta and umbilical blood were collected at GD 165. Western blot was used to determine the phosphorylation of proteins in the mTOR, insulin/IGF-I, ERK1/2, and GSK-3 signaling pathways in placental homogenates and expression of glucose transporter 1 (GLUT-1), taurine transporter (TAUT), sodium-dependent neutral amino acid transporter (SNAT), and large neutral amino acid transporter (LAT) isoforms in syncytiotrophoblast microvillous membranes (MVMs). MNR reduced fetal weights by 13%, lowered fetal plasma concentrations of essential amino acids, and decreased the phosphorylation of placental S6K, S6 ribosomal protein, 4E-BP1, IRS-1, Akt, ERK-1/2, and GSK-3. MVM protein expression of GLUT-1, TAUT, SNAT-2 and LAT-1/2 was reduced in MNR. This is the first study in primates exploring placental responses to maternal undernutrition. Inhibition of placental mTOR and insulin/IGF-I signaling resulting in down-regulation of placental nutrient transporters may link maternal undernutrition to restricted fetal growth.
authors: 2Center for Pregnancy and Newborn Research, Department of Obstetrics and Gynecology, University of Texas Health Science Center San Antonio, Mail Code 7836, 7703 Floyd Curl Dr., San Antonio, TX 78229-3900, USA. josephf@uthscsa.edu.
authors: Jovita V
authors: JV
authors: Kavitha
authors: Fredrick J
authors: FJ
authors: Rosario
authors: Mark J
authors: MJ
authors: Nijland
authors: Thomas J
authors: TJ
authors: McDonald
authors: Guoyao
authors: G
authors: Wu
authors: Yoshikatsu
authors: Y
authors: Kanai
authors: Theresa L
authors: TL
authors: Powell
authors: Peter W
authors: PW
authors: Nathanielsz
authors: Thomas
authors: T
authors: Jansson
mesh_terms: D000818:Animals; D015536:Down-Regulation; D005260:Female; D007328:Insulin / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D010215:Papio; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000502:physiology*
chemical_list: D007328:Insulin; D007334:Insulin-Like Growth Factor I; D058570:TOR Serine-Threonine Kinases
keywords: fetal growth restriction; nonhuman primate; trophoblast