Developmental exposure to an environmentally relevant dose of Bisphenol S impairs postnatal growth and disrupts placental transcriptional profile in female rat

Because of its possible adverse effects on human health and its ubiquitous nature, Bisphenol A (BPA) is gradually being replaced by presumably safer alternatives like Bisphenol S (BPS). However, data regarding the effects of developmental exposure to BPS on pregnancy and fetal outcomes are very scarce. Here we show that perinatal exposure to BPS at a very low dose significantly impairs postnatal growth and affects the placental transcriptome in rats. Oral exposure one week before mating and during gestation and lactation to a very low dose of BPS (25 ng/kg/day) is associated with impaired postnatal growth without significant difference in fetal weight on gestational day 18 in females. In contrast, in males, exposure to BPS 25 decreased fetal weight on gestational day 18 but growth restriction did not persist into adulthood. In female, exposure to this very low dose of BPS decreased the placental mRNA expression of fucosyltransferase2 (Fut2), pregnancy-specific glycoprotein 22 (Psg22), Wnt family member 7b (Wnt7b) which are involved in early placental development. Placental DNA methylation of steroid receptor coactivator 2 (src2), a key mediator of steroid induced decidualization, was significantly reduced, while placental src2 mRNA expression was unaffected. These results suggest that early exposure to a very low dose of BPS has long term consequences on growth trajectory and is associated with placental dysregulation.