Comparing effects and action mechanisms of BPA and BPS on HTR-8/SVneo placental cells†

Abstract

Bisphenol A (BPA) is one of the most investigated compound as a suspected endocrine disrupting chemical. It has been found at nM concentrations in the maternal serum, cord serum, and amniotic fluid and also permeates placental tissues. Attempts are being made to replace BPA with the analog Bisphenol S (BPS). Also BPS was found in maternal and umbilical cord serum, and urine samples from a large population of pregnant women. A few studies investigated BPA impact on the placentation process, and even less are available for BPS. This work aimed to elucidate and compare the effects of BPA and BPS on physiological functions of HTR-8/SVneo cells, derived from extravillous trophoblast of first-trimester pregnancy. Proliferation and migration ability of trophoblast cells were assessed in vitro after exposure to BPA or BPS (10-13-10-3 M). Further, induction of the inflammatory response by the bisphenols was studied. To provide insight into the molecular pathways implicated in the responses, experiments were carried out in the presence or absence of tamoxifen as estrogen receptors (ERs) blocker, and U0126 as ERK1/2 phosphorylation inhibitor. Data indicate that BPA significantly affects both proliferation and migration of HTR-8/SVneo cells, through ER and ERK1/2 mediated processes. Differently, BPS only acts on proliferation, again through ER and ERK1/2 mediated processes. BPS, but not BPA, induces secretion of interleukins 6 and 8. Such effect is inhibited by blocking ERK1/2 phosphorylation. To the best of our knowledge, these are the first data showing that BPS affects trophoblast functions through ER/MAPK modulation.

Keywords: BPA; BPS; Endocrine disruptors; HTR-8/SVneo cells; Human trophoblast; MAPK.