Abstract
Triclosan (TCS) has garnered significant attention due to its widespread use and associated endocrine-disrupting effects. However, its impact on the neuroendocrine system and underlying mechanisms remain poorly understood. Here, we established correlations between TCS exposure and serum sex hormone levels in participants of the National Health and Nutrition Examination Survey (NHANES). Additionally, we investigated TCS's influence on the neuroendocrine system using adult zebrafish exposed to environmentally relevant concentrations of TCS (0.361-48.2 μg/L) for 21 days. Assessment of reproductive and neurotoxicity included histopathological examination and behavioral tests. Transcriptomics, proteomics analyses, and biochemical detection were employed to elucidate mechanisms underlying TCS-induced neuroendocrine disruption. Significant correlations were found between TCS exposure and estradiol, testosterone, and sex hormone-binding globulin levels in NHANES participants. In addition, TCS exposure inhibited ovary development and spermatogenesis in zebrafish. Transcriptomics and proteomics analysis revealed gender-specific key signaling and metabolism-related pathways implicated in TCS-induced reproductive toxicity. Moreover, TCS exposure induced nervous system impairment, as evidenced by histological changes and altered motor behavior, possibly associated with oxidative damage. Correlation analysis further highlighted the potential connection between endocrine system disruption and nervous system impairment following TCS exposure. Overall, this study provided evidence supporting TCS-induced endocrine disruption and offered insights into its underlying mechanisms.