Effects of prenatal hypoxia on placental glucocorticoid barrier: Mechanistic insight from experiments in rats

Prenatal hypoxia is the most common stress in mid-late gestation that usually arise from maternal, placental and/or fetal factors. As a multifunctional organ enabling optimal fetal growth, placenta must adapt to diverse environmental stressors. Excessive glucocorticoids exposure is known to have adverse effects on fetal growth. The fetus is shielded by a placental glucocorticoid barrier by 11 beta-hydroxysteroid dehydrogenase 2 (11 beta-HSD2). However, the effects and underlying mechanisms of intrauterine hypoxia on placental glucocorticoid barrier are largely unknown. This study was the first to determine the effects and its mechanisms. Pregnant rats were exposed to hypoxia (10.5% O2) from gestational day (GD)10-20. At GD20, expression of 11-beta HSD2 were determined in placenta, and corticosterone levels were measured in maternal and fetal plasma. Prenatal hypoxia disrupted the placental glucocorticoid barrier by suppressing 11-beta HSD2 expression. Meanwhile, the decreased 11-beta HSD2 was correlated with an increased DNA methylation within its gene promoter. Together, these results indicated that prenatal hypoxia impair placental glucocorticoid barrier, was strongly associated with reprogrammed 11-beta HSD2 expression via a DNA methylation-mediated epigenetic mechanism.