title: Prenatal testosterone-induced fetal growth restriction is associated with down-regulation of rat placental amino acid transport.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, The University of Texas Medical Branch Galveston, Texas, USA. kusathis@utmb.edu
authors.forename: Kunju
authors.initials: K
authors.lastname: Sathishkumar
authors.forename: Rebekah
authors.initials: R
authors.lastname: Elkins
authors.forename: Vijayakumar
authors.initials: V
authors.lastname: Chinnathambi
authors.forename: Haijun
authors.initials: H
authors.lastname: Gao
authors.forename: Gary D V
authors.initials: GD
authors.lastname: Hankins
authors.forename: Chandra
authors.initials: C
authors.lastname: Yallampalli
mesh_terms: D026924:Amino Acid Transport System A / Q000096:biosynthesis; D026905:Amino Acid Transport Systems / Q000235:genetics*; D000596:Amino Acids / Q000097:blood / Q000378:metabolism; D000818:Animals; D001724:Birth Weight / Q000187:drug effects; D015536:Down-Regulation; D005260:Female; D005317:Fetal Growth Retardation / Q000139:chemically induced / Q000503:physiopathology*; D010920:Placenta / Q000187:drug effects / Q000503:physiopathology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000097:blood / Q000494:pharmacology*
chemical_list: D026924:Amino Acid Transport System A; D026905:Amino Acid Transport Systems; D000596:Amino Acids; C412568:Slc38a2 protein, rat; D013739:Testosterone