title: Antenatal dexamethasone treatment in midgestation reduces system A-mediated transport in the late-gestation murine placenta.
abstract: Clinically, approximately 30% of women who receive synthetic glucocorticoids (sGC) for risk of preterm labor carry to term. In vitro studies have shown that sGC acutely regulate the placental system A amino acid transporter, but there are no comparable data in vivo. Hence, the objective of our study was to examine the acute [embryonic day (E)15.5] and longer-term (E17.5 and E18.5) consequences of midgestation antenatal sGC [dexamethasone (DEX); 0.1 mg/kg on E13.5 and E14.5] on placental system A-mediated transfer in the mouse (measured in vivo as maternal-fetal unidirectional (14)C-methylaminoisobutyric acid transfer per gram of placenta). System A transfer and Slc38a mRNA expression significantly increased from E12.5 to E18.5 (P < 0.05), corresponding to increased fetal growth. DEX treatment had no acute effect at E15.5 or longer-term effect at E17.5 but significantly decreased system A-mediated transfer before term (E18.5; P < 0.05) in placentae of male and female fetuses. There was no effect of DEX on Slc38a gene expression. Administration of DEX in this regime had no effect on birth weight. We conclude that sGC treatment in midgestation leads to a substantial decrease in placental system A-mediated transport in late gestation, suggesting that prenatal sGC therapy may lead to a reduction in availability of neutral amino acids to the fetus if gestation persists to term.
authors: Department of Physiology, University of Toronto, 1 Kings College Circle, Medical Sciences Building Room 3360, Toronto, Ontario, Canada M5S 1A8. m.audette@utoronto.ca
authors: Melanie C
authors: MC
authors: Audette
authors: John R G
authors: JR
authors: Challis
authors: Rebecca L
authors: RL
authors: Jones
authors: Colin P
authors: CP
authors: Sibley
authors: Stephen G
authors: SG
authors: Matthews
mesh_terms: D026924:Amino Acid Transport System A / Q000378:metabolism*; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005938:Glucocorticoids / Q000494:pharmacology*; D008297:Male; D008431:Maternal-Fetal Exchange; D051379:Mice; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy
chemical_list: D026924:Amino Acid Transport System A; D005938:Glucocorticoids; D003907:Dexamethasone