Exploring potential toxicological pathways of triclosan in human ovarian dysfunction via integrated network toxicology and experimental validation

Triclosan (TCS), a compound ubiquitous in personal care products, is now a prevalent environmental contaminant across various ecosystems and has been detected in human tissue samples. Despite its prevalence and strong association with female infertility, the mechanisms by which TCS induces ovarian toxicity have not been thoroughly studied. This study employed an integrated approach combining network toxicology, molecular docking, transcriptomics, and cell experiments to systematically investigate the molecular mechanisms linking TCS to two core ovarian dysfunction diseases: polycystic ovary syndrome (PCOS) and premature ovarian insufficiency (POI). The physicochemical properties and multi-organ toxicity of TCS were predicted using ADMETlab 3.0 and SwissADME. Following the retrieval of TCS, PCOS, and POI-associated targets from public databases, a PPI network was built to pinpoint central hubs. Subsequently, GO and KEGG enrichment analyses were conducted to delineate implicated biological pathways. Molecular docking was conducted to evaluate the binding affinity of TCS to core proteins. Transcriptomic analysis was performed on the ovarian granulosa cell line KGN exposed to 10 μM TCS, a concentration close to human exposure levels. Cell biology experiments were further employed to validate the findings. The network toxicology results indicated that TCS induces ovarian toxicity primarily by promoting apoptosis and triggering inflammatory responses. Key targets identified included AKT1, EGFR, TNF, IL6, and CASP3, which exhibited strong binding affinities, suggesting direct interactions. Transcriptomic analyses further confirmed disruptions in cytokine receptor binding and apoptosis pathways. Cell experiments confirmed that TCS exposure significantly promotes apoptosis and increases the production of inflammatory cytokines in two types of ovarian granulosa cell lines, SVOG and KGN. Overall, this study provides a conceptual framework for TCS-induced ovarian dysfunction and offers new insights for future research on the mechanisms underlying the ovarian toxicity of TCS.