Integrated Proteomic and Phosphoproteomic Profiling Reveals Mechanisms of Bisphenol A Induced Placental Toxicity.

The global industrialization and rapid urbanization have elevated the risk of toxic pollutant exposure, which affects human health, especially during pregnancy. Pregnant mothers are daily exposed to bisphenol A (BPA), a common plastic leachate and a prominent toxic pollutant present in our environment. BPA acts as an endocrine-disrupting chemical (EDC) by altering feto-placental homeostasis. This persistent and potent exposure to BPA during gestation can trigger placental damage, affecting trophoblast cell function and survival. BPA even disrupts specific signaling cascades by altering post-translational protein phosphorylation. However, this BPA-mediated dysregulation of signaling nodes in the early trimester placenta remains unexplored. Therefore, this study investigates the global proteome changes in post-BPA-exposed extravillous trophoblast (EVT) cells, which revealed a BPA-mediated dynamic regulation of phospho-proteome signatures and their associated kinases. Further inspection shows that the altered phosphorylation of c-JUN (S63) and GSK3α (Y279) is associated with BPA toxicity in EVTs and the placenta. This altered phosphorylation affects cellular signaling downstream, imparting damage upon the growing feto-placental unit. This highlights an altered phosphorylation-mediated mechanism of BPA toxicity in the placenta, which can cause the onset of adverse pregnancy outcomes. Data are available via ProteomeXchange with the identifiers PXD074780 and PXD080006.