Prenatal BPA exposure disrupts androgen synthesis in testicular Leydig cells via epigenetic modifications of steroidogenic factor 1.

Prenatal exposure to bisphenol A (BPA) adversely affects testicular development and interferes with androgen synthesis in male offspring. This study explored the epigenetic mechanisms underlying BPA-induced testicular dysfunction using TM3 Leydig cells and offspring exposed to BPA during gestation. High-dose BPA treatment led to decreased testicular weight, disorganization of seminiferous tubules, and reduced testosterone production. Transcriptomic profiling demonstrated downregulation of Steroidogenic Factor 1 (Sf1) and suppression of critical steroidogenic pathways. These molecular alterations were accompanied by hypermethylation of the Sf1 promoter, indicating transcriptional silencing through DNA methylation. Consistent epigenetic and transcriptional changes were also detected in the testes of BPA-exposed offspring. In summary, these findings identify epigenetic regulation of Sf1 as a central mechanism through which prenatal BPA exposure impairs androgen biosynthesis, offering new insight into the molecular basis of environmental endocrine disruption.