Exposure to Bisphenol B and S Increases the Risk of Male Reproductive Dysfunction in Middle Age

Area of Science:

• Endocrinology
• Toxicology
• Molecular Biology

Background:

• Bisphenol A (BPA) analogs like bisphenol B (BPB) and bisphenol S (BPS) are linked to male reproductive dysfunction (MRD).
• The role of BPA analogs in MRD among middle-aged men remains unclear.
• Representative MRD conditions include cryptorchidism, erectile dysfunction, premature ejaculation, and testicular tumors.

Purpose of the Study:

• To investigate the molecular mechanisms by which BPB and BPS induce MRD in middle-aged males.
• To identify core molecular targets and pathways affected by bisphenol exposure.
• To provide data for the safety assessment of BPB and BPS.

Main Methods:

• Bioinformatic analysis using GeneCards, STRING, and Cytoscape to identify hub genes (TP53, AKT1, MYC).
• Enrichment analysis to determine disrupted pathways (steroidogenesis).
• UPLC-MS/MS to quantify BPB and BPS accumulation in testes.
• In vivo exposure studies to assess effects on testosterone levels and gene expression.
• Molecular docking to predict interactions with cytochrome P450 enzymes.

Main Results:

• TP53, AKT1, and MYC were identified as core targets associated with MRD.
• Bisphenols (BPs) were found to disrupt steroidogenesis.
• BPB and BPS accumulate in testicular tissue.
• Exposure to BPB or BPS decreased testosterone levels and hub gene expression.
• Molecular docking confirmed BPB and BPS bind to cytochrome P450 enzymes, potentially inhibiting sex hormone synthesis.

Conclusions:

• BPB and BPS induce MRD in middle-aged males by disrupting steroidogenesis and accumulating in the testes.
• The identified molecular targets and pathways provide a mechanistic understanding of bisphenol-induced reproductive toxicity.
• These findings are crucial for evaluating the reproductive health risks associated with BPB and BPS exposure.