[Mechanisms of bisphenol P and bisphenol Z in male spermatogenesis dysfunction: A network toxicology, molecular docking and bioinformatics study].

Abstract

ObjectiveTo investigate the effects and molecular mechanisms of bisphenol P (BPP) and bisphenol Z (BPZ) on male spermatogenic disorder (SD).MethodsCommon targets of BPP/BPZ and SD were screened by network toxicology. Bioinformatics methods were applied to construct protein-protein interaction (PPI) networks and perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Molecular docking was used to evaluate the binding affinity of BPP and BPZ to core targets, as well as GEO database analysis was conducted to validate the expression of key genes in SD patients.ResultsThrough network toxicological analysis in this study, it was found that BPP and BPZ have 58 and 48 co-action targets with SD respectively. The MCODE algorithm revealed core functional modules associated with tumor progression, hormone signaling, and steroid metabolism. GO and KEGG enrichment analyses indicated that these targets were mainly involved in biological processes such as protein phosphorylation, hormone response, steroid synthesis, and regulation of the cell cycle and apoptosis, and were mostly located in the cytoplasm and nucleus. Molecular docking demonstrated strong binding affinity of BPP and BPZ to key targets such as BCL2, ESR1, and PARP1. Furthermore, GEO data analysis showed significant alterations in the expression of several core genes in SD patients.ConclusionBPP and BPZ may contribute to SD by interfering with hormone-related signaling pathways, as well as dysregulating cell cycle progression and apoptotic processes.

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