Integrative multi-omics analysis reveals FAAH and LIPE as candidate targets in OBS-induced spermatogenic and fertility impairment

Background Sodium p-perfluorous nonenoxybenzene sulfonate (OBS) is an emerging polyfluoroalkyl ether sulfonate with environmental persistence and potential biological toxicity. However, its effects on male reproductive health and associated molecular alterations remain poorly understood.Methods Network toxicology, transcriptomic and single-cell transcriptomic analyses, data-independent acquisition-based proteomics, molecular docking, and mouse experiments were integrated to investigate OBS-associated spermatogenic toxicity.Results FAAH and LIPE were prioritized as candidate targets potentially associated with OBS-induced spermatogenic impairment. In human non-obstructive azoospermia datasets, FAAH and LIPE were downregulated and showed discriminatory ability between affected and control samples. Molecular docking predicted potentially favorable interaction conformations between OBS and the two proteins. In mice, exposure to 0.5 or 2.5 mg/kg OBS was associated with disrupted seminiferous tubule architecture, impaired sperm quality, reduced testicular FAAH and LIPE expression, and fewer offspring after mating.Conclusion OBS exposure was associated with impaired spermatogenesis and reduced male reproductive performance in mice. FAAH and LIPE may be involved in OBS-associated testicular injury, although their functional roles and direct interactions with OBS require further experimental validation. These findings provide additional evidence of the male reproductive toxicity of OBS and highlight the need for continued evaluation of emerging PFAS alternatives.