Multidimensional mechanistic analysis elucidates spermatogenesis disruption induced by bisphenol S

Area of Science:

• Reproductive Toxicology
• Environmental Health
• Computational Biology

Background:

• Bisphenol S (BPS) is a widespread substitute for Bisphenol A, raising concerns about global environmental exposure.
• The impact of BPS on spermatogenesis disruption (SD) and its underlying molecular mechanisms remain incompletely understood.

Purpose of the Study:

• To comprehensively elucidate the molecular mechanisms by which BPS induces spermatogenesis disruption.
• To identify potential diagnostic biomarkers and therapeutic targets for BPS-induced reproductive toxicity.

Main Methods:

• Employed a multidimensional computational strategy integrating network toxicology, bioinformatics, machine learning, single-cell analysis, and biomolecular modeling.
• Utilized 113 machine learning algorithm combinations for systematic screening.
• Analyzed testicular tissue-specific co-expression networks and single-cell data.

Main Results:

• BPS disrupts spermatogenesis by interfering with signaling pathways (cAMP, MAPK, VEGF, PI3K-Akt), forming a synergistic toxic network.
• CTSK, GSTZ1, and PDE4D were identified as core diagnostic biomarkers for SD and potential BPS hub targets.
• Hub genes are specifically expressed in testicular reproductive cell types and show strong binding affinity with BPS.

Conclusions:

• This study provides critical insights into the reproductive toxicity risk of BPS, elucidating its impact on spermatogenesis.
• Identified novel biomarkers (CTSK, GSTZ1, PDE4D) and potential intervention targets for BPS-induced reproductive harm.
• Advances the understanding of BPS reproductive toxicology through multidimensional mechanistic analysis.