Vitargent (China)

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.

Phthalates are commonly used in plastic products in daily life. The endocrine-disrupting effects of phthalates have been widely reported. Accumulating evidence from human cohorts and lab animals indicate exposure to phthalates might impair neurodevelopment. However, the direct causal relationship and mechanism between phthalates with neurodevelopment and neurotoxicity have not been firmly established. We found that phthalates (i.e. DBP, DINP, BBP) disrupted the expression of estrogen receptors (esr1, esr2a, esr2b), and impaired neurogenesis in the brain of zebrafish during embryonic development. Moreover, the abnormal expression of estrogen receptors, especially esr2a, was partly rescued in zebrafish which exposed to phthalates, with the estrogen receptor antagonist tamoxifen. Hence, impaired neurogenesis of zebrafish exposed to phthalates was partly reversed by tamoxifen treatment. Moreover, our results show that induced pluripotent stem cells (iPSC)-derived human neurons exposed to phthalates triggered double-strand DNA breaks in vitro. Overall, this study demonstrates that exposure to phthalates affects neurodevelopment in zebrafish embryos and induces neurotoxicity in human neurons partly through disrupting the expression of estrogen receptors.