Differential susceptibility of Leydig and Sertoli cells to bisphenol A

Bisphenol A (BPA) is an endocrine-disrupting chemical that is increasingly becoming a vital factor in public health due to its ubiquity and toxicity. BPA is associated with male infertility via the disrupted function of Leydig and Sertoli cells. Despite extensive research, the current understanding of the specific pathological concentrations and the mechanisms following BPA exposure still remain questionable. Therefore, we investigated the susceptibilities and underlying mechanisms in Leydig and Sertoli cells following treatment with various BPA doses (0.0001–100 µM in a 10-fold serial dilution). Our results showed that the lowest BPA levels (10⁻⁴ μM) decreased mitochondrial membrane potential and ATP levels. In contrast, ROS levels were increased at high BPA levels regardless of exposure time (24 or 48 h) in both cell types. Mitochondrial-mediated apoptosis was identified along with increased ROS levels and abnormal mitochondrial dynamics, but both cell types showed different susceptibility to BPA toxicity. Subsequently, BPA had detrimental impacts on the mRNA expression levels of steroidogenic enzymes and testosterone synthesis in Leydig cells and reduced anchoring junction proteins in Sertoli cells. Consequently, our results demonstrated that both cells were affected via estrogen receptor alpha. However, protein kinase A was oppositely expressed following BPA exposure in each cell type. Therefore, it is plausible to suggest that each cell has distinct sensitivities and mechanisms in response to BPA.