Prenatal testosterone-induced fetal growth restriction is associated with down-regulation of rat placental amino acid transport
Year: 2011
Type: article
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: Kunju Sathishkumar, Rebekah Elkins, Vijayakumar Chinnathambi, Haijun Gao, Gary DV Hankins, Chandra Yallampalli
Institution: The University of Texas Medical Branch at Galveston
Language: English
Subfield: Obstetrics and Gynecology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,690
Awards: G2494798318, G2663282175, Sex-specific fetal programming of adult vascular dysfunction and hypertension, Sex Steroid Hormones and Calcitonin Gene-Related Peptide, Maternal Androgen Excess: Vascular and Placental Function and Fetal Consequences, Low birth weight, uterine infection, and nitric oxide, G969960702
OpenAlex ID: W2162300184