PMID- 21812961 OWN - NLM STAT- MEDLINE DCOM- 20111122 LR - 20211020 IS - 1477-7827 (Electronic) IS - 1477-7827 (Linking) VI - 9 DP - 2011 Aug 3 TI - Prenatal testosterone-induced fetal growth restriction is associated with down-regulation of rat placental amino acid transport. PG - 110 LID - 10.1186/1477-7827-9-110 [doi] AB - BACKGROUND: Exposure of pregnant mothers to elevated concentrations of circulating testosterone levels is associated with fetal growth restriction and delivery of small-for-gestational-age babies. We examined whether maternal testosterone crosses the placenta to directly suppress fetal growth or if it modifies placental function to reduce the capacity for transport of nutrients to the fetus. METHODS: Pregnant rats were exposed to testosterone propionate (TP; 0.5 mg/kg) by daily subcutaneous injection from gestational days (GD) 15-19. Maternal and fetal testosterone levels, placental nutrient transport activity and expression of transporters and birth weight of pups and their anogenital distances were determined. RESULTS: This dose of TP doubled maternal testosterone levels but had no effect on fetal testosterone levels. Maternal daily weight gain was significantly lower only on GD 19 in TP treated dams compared to controls. Placental weight and birth weight of pups were significantly reduced, but the anogenital distance of pups were unaffected by TP treatment. Maternal plasma amino acids concentrations were altered following testosterone exposure, with decreases in glutamine, glycine, tyrosine, serine, proline, and hydroxyproline and increases in asparagine, isoleucine, leucine, lysine, histidine and arginine. In the TP dams, placental system A amino acid transport activity was significantly reduced while placental glucose transport capacity was unaffected. Decreased expression of mRNA and protein levels of slc38a2/Snat2, an amino acid transporter, suggests that reduced transporter proteins may be responsible for the decrease in amino acid transport activity. CONCLUSIONS: Taken together, these data suggest that increased maternal testosterone concentrations do not cross the placenta to directly suppress fetal growth but affects amino acid nutrient delivery to the fetus by downregulating specific amino acid transporter activity. FAU - Sathishkumar, Kunju AU - Sathishkumar K AD - Department of Obstetrics and Gynecology, The University of Texas Medical Branch Galveston, Texas, USA. kusathis@utmb.edu FAU - Elkins, Rebekah AU - Elkins R FAU - Chinnathambi, Vijayakumar AU - Chinnathambi V FAU - Gao, Haijun AU - Gao H FAU - Hankins, Gary D V AU - Hankins GD FAU - Yallampalli, Chandra AU - Yallampalli C LA - eng GR - R03 HD069750/HD/NICHD NIH HHS/United States GR - HD069750/HD/NICHD NIH HHS/United States GR - HL72650/HL/NHLBI NIH HHS/United States GR - R01 HL119869/HL/NHLBI NIH HHS/United States GR - HL58144/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20110803 PL - England TA - Reprod Biol Endocrinol JT - Reproductive biology and endocrinology : RB&E JID - 101153627 RN - 0 (Amino Acid Transport System A) RN - 0 (Amino Acid Transport Systems) RN - 0 (Amino Acids) RN - 0 (Slc38a2 protein, rat) RN - 3XMK78S47O (Testosterone) SB - IM MH - Amino Acid Transport System A/biosynthesis MH - Amino Acid Transport Systems/*genetics MH - Amino Acids/blood/metabolism MH - Animals MH - Birth Weight/drug effects MH - Down-Regulation MH - Female MH - Fetal Growth Retardation/chemically induced/*physiopathology MH - Placenta/drug effects/physiopathology MH - Pregnancy MH - Rats MH - Rats, Sprague-Dawley MH - Testosterone/blood/*pharmacology PMC - PMC3162507 EDAT- 2011/08/05 06:00 MHDA- 2011/12/13 00:00 PMCR- 2011/08/03 CRDT- 2011/08/05 06:00 PHST- 2011/04/13 00:00 [received] PHST- 2011/08/03 00:00 [accepted] PHST- 2011/08/05 06:00 [entrez] PHST- 2011/08/05 06:00 [pubmed] PHST- 2011/12/13 00:00 [medline] PHST- 2011/08/03 00:00 [pmc-release] AID - 1477-7827-9-110 [pii] AID - 10.1186/1477-7827-9-110 [doi] PST - epublish SO - Reprod Biol Endocrinol. 2011 Aug 3;9:110. doi: 10.1186/1477-7827-9-110.