Environmentally relevant low-dose bisphenol A enhances invasion of human extravillous trophoblasts with associated increases in MMP activity.

Bisphenol A (BPA), a widespread environmental endocrine-disrupting chemical, has been implicated in adverse effects on placental development and pregnancy outcomes. However, the impact of environmentally relevant low-dose BPA on human trophoblast function remains unclear. Here, we examined the effects of BPA on distinct trophoblast functions using multiple human trophoblast models. BeWo cells, a choriocarcinoma-derived model of syncytiotrophoblast (ST) differentiation, were used to assess the effects of BPA on ST formation, which was not significantly altered. In addition, the effects of BPA on trophoblast lineage differentiation toward either ST or extravillous trophoblast (EVT) were evaluated using a cytotrophoblast-derived in vitro differentiation model, with no significant impact observed. In contrast, HTR-8/SVneo cells, an immortalized first-trimester extravillous trophoblast (EVT) cell line commonly employed to study trophoblast migration and invasion, exhibited significantly enhanced motility upon exposure to 1 nM BPA, as demonstrated by wound healing and transwell assays. Gelatin zymography revealed a slight increase of matrix metalloproteinases (MMP-2 and MMP-9) activity, suggesting a potential mechanism for increased invasiveness. These findings provide evidence that environmentally relevant low-dose BPA can promote EVT migration and invasion, accompanied by a modest increase in MMP activity, highlighting a potential pathway by which environmental BPA exposure may influence placental function and pregnancy outcomes.