Appiah, E.; Salamah, J.; Cheeran, E.; Lee, B.-K.

Bisphenol S (BPS) is currently used in the manufacturing of several household equipment such as water pipes and food containers. Hence, its entrance into the human body is almost inevitable. The presence of BPS in body fluids has been reported. However, its potential toxicity, especially on human placenta development and pregnancy progression, has not been explored. In this study, we assessed the impacts of BPS on self-renewal and differentiation potentials of trophoblast stem cells (TSCs) by exposing them to three different BPS concentrations during both self-renewal and differentiation of TSCs into syncytiotrophoblast (ST), extravillous trophoblast (EVT), and trophoblast organoids. Interestingly, BPS treatment did not affect the proliferation, cell cycle, and stemness of the TSCs but it led to induction of apoptosis in each trophoblast lineage. BPS altered the expression of several fusion-related genes. However, this alteration did not translate into significant morphological defects in the STs and organoids. Moreover, BPS did not impair the differentiation of TSCs into EVTs. These findings suggest that the presence of BPS at the feto-maternal interface may exaggerate trophoblast apoptosis and moderately inhibit the trophoblast fusion pathway to affect placenta development and pregnancy. Our study offers valuable insights into the toxicity of BPS on human placenta development, emphasizing the need for further research on the relationship between maternal serum levels of BPS and pregnancy complications.