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

Reproductive Biology and Endocrinology

Research

Haijun Gao¹  Vijayakumar Chinnathambi¹  Gary DV Hankins¹  Rebekah Elkins¹  Chandra Yallampalli¹  Kunju Sathishkumar¹ 

[1] Department of Obstetrics and Gynecology, The University of Texas Medical Branch Galveston, Texas, USA;

关键词: Testosterone;    Testosterone Level;    Fetal Growth;    Fetal Growth Restriction;    Testosterone Propionate;   

DOI  :  10.1186/1477-7827-9-110

 received in 2011-04-13, accepted in 2011-08-03,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundExposure 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.MethodsPregnant 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.ResultsThis 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.ConclusionsTaken 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.

【 授权许可】

CC BY   
© Sathishkumar et al; licensee BioMed Central Ltd. 2011