Bisphenols (BPs), are extensively utilized in various manufacturing industries, leading to increased human exposure and detection in diverse environments, posing potential risks to reproductive health. This study endeavors to investigate whether seven BP compounds result in male spermatogenesis disorder (SD) and explore the underlying molecular mechanisms involved. Network toxicology was integrated with molecular docking technology and bioinformatics data to systematically elucidate the roles, underlying targets and pathological mechanisms of each BP compound in the SD process. Network toxicology analysis revealed that all seven BPs induced SD through similar mechanisms. The protein-protein interaction (PPI) network identified key targets implicated in SD induced by each BP, while enrichment analysis highlighted that BPs primarily affected SD through hormone-dependent pathways, cell proliferation, apoptosis, and prostate cancer pathways. Molecular docking further confirmed the pivotal role of these targets in BPs-induced SD. Additionally, analysis of Gene Expression Omnibus (GEO) data demonstrated significant differential expression of these genes in the SD patients compared to normal controls. These results underscored the crucial effects of genes such as BCL2, PARP1, AKT1, EGFR, ESR1, ESR2, HIF1A, HSP90AA1 and GSK3B in the development of SD. Collectively, these findings indicated that BPs exposure could contribute to the onset of SD as an environmental trigger, while offering theoretical insights into the molecular mechanisms associated with BPs-elicited SD.
Tian et al. (Tue,) studied this question.