Abstract

Bisphenol compounds are recognized as persistent environmental pollutants and are strongly linked to various adverse pregnancy outcomes. Despite research progress on the reproductive toxicity of BPA on the ovaries and oocytes, the impact of BPA-related compounds on placental development remains unclear. In our study, BPA/BPS exposure induced structural abnormalities and dysfunction in nutrient transport within the placenta of pregnant mice, significantly inhibiting on the proliferation and migration of porcine trophoblast cells (PTR2), and increased apoptosis. Besides, BPA exposure resulted in upregulation of E-cadherin protein expression and the downregulation of fibronectin, vimentin, and ZEB2 protein expression. Additionally, BPA/BPS exposure also impaired angiogenesis of porcine vascular endothelial cells (PVEC). Mechanistically, BPA/BPS activated the endoplasmic reticulum stress (ERS) signaling pathway by enhancing p-eIF2α protein expression, which subsequently interfered with the epithelial-mesenchymal transition (EMT) process. Importantly, 4-phenylbutyric acid (4-PBA) and Salubrinal reversed these adverse effects, promoting EMT process and angiogenesis. Collectively, our study elucidates a novel ERS-EMT signaling axis as a potential mechanism underlying bisphenol-induced placental dysfunction.