Using experimental models to assess effects of Bisphenol A (BPA) and phthalates on the placenta: Challenges and perspectives

The placenta is critical for all aspects of fetal development. Bisphenol A (BPA) and phthalates are endocrine disruptors with ubiquitous exposure in pregnant women—their effects on the placenta is an area of growing research interest. Therefore, our objectives were to (1) summarize research related to the effects BPA or phthalates on placental outcomes in animal and cell models, and (2) evaluate the challenges for using such models to study the impacts of these chemicals on placental endpoints. Overall, studies in cells and animal models suggest that BPA and phthalates impact placental hormones, some epigenetic endpoints, increase inflammation and oxidative stress, and decrease cell viability and nutrient transfer. However, few animal or cell studies have assessed these outcomes at concentrations relevant to humans. Furthermore, it is unclear whether effects of BPA/phthalates on the placenta in animal models mediate fetal outcomes, as most studies have dosed after the earliest stages of placental and fetal development. It is also unclear whether effects of these chemicals are sex-specific, as few studies have considered placental sex. Finally, while there is substantial evidence for effects of mono-(2-ethylhexyl) phthalate (the major metabolite of di-(2-ethylhexyl) phthalate), on placental endpoints in cells, little is currently known about effects of other phthalates to which pregnant women are exposed. Moving forward, these limitations will need to be addressed to help us understand the precise mechanisms of action of these chemicals within the placenta, and how these reported perturbations impact fetal health.