Prenatal testosterone-induced fetal growth restriction is associated with down-regulation of rat placental amino acid transport

Kunju Sathishkumar, Rebekah Elkins, Vijayakumar Chinnathambi, Haijun Gao, Gary Hankins, Chandra Yallampalli

Research output: Contribution to journalArticle

54 Citations (Scopus)

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.

Original languageEnglish
Article number110
JournalReproductive Biology and Endocrinology
Volume9
DOIs
StatePublished - Aug 3 2011

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Fetal Development
Testosterone
Down-Regulation
Amino Acids
Mothers
Amino Acid Transport Systems
Birth Weight
Food
Placenta
Fetus
Testosterone Propionate
Isoleucine
Asparagine
Hydroxyproline
Subcutaneous Injections
Glutamine
Histidine
Proline
Leucine
Glycine

ASJC Scopus subject areas

  • Developmental Biology
  • Endocrinology
  • Reproductive Medicine
  • Medicine(all)

Cite this

Prenatal testosterone-induced fetal growth restriction is associated with down-regulation of rat placental amino acid transport. / Sathishkumar, Kunju; Elkins, Rebekah; Chinnathambi, Vijayakumar; Gao, Haijun; Hankins, Gary; Yallampalli, Chandra.

In: Reproductive Biology and Endocrinology, Vol. 9, 110, 03.08.2011.

Research output: Contribution to journalArticle

Sathishkumar, Kunju ; Elkins, Rebekah ; Chinnathambi, Vijayakumar ; Gao, Haijun ; Hankins, Gary ; Yallampalli, Chandra. / Prenatal testosterone-induced fetal growth restriction is associated with down-regulation of rat placental amino acid transport. In: Reproductive Biology and Endocrinology. 2011 ; Vol. 9.
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