Evaluation of the effects of low nanomolar bisphenol A-like compounds’ levels on early human embryonic development and lipid metabolism with human embryonic stem cell in vitro differentiation models

The widely used chemical bisphenol A (BPA) has been associated with several health effects. In recent years, many derivatives were developed to replace BPA without thorough toxicological evaluation. Here, we employed a human embryoid body (EB)-based in vitro global differentiation and hepatic specification models, followed by RNA-seq analyses, to comprehensively study the potential developmental toxicity of six BPA replacements (BPS, BPF, BPZ, BPB, BPE, and BPAF), as compared to BPA. We found that bisphenols may disrupt lineage commitment and lipid metabolism during early embryonic development. These effects mostly manifested via the dysregulation of HOX and APO family genes. Moreover, among the seven bisphenols analyzed, BPE, due to lower potential developmental toxicity, stood out as a relatively safe substitute of BPA in many applications, especially for infant/baby products.