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Exposure to oxygenated polycyclic aromatic hydrocarbons and endocrine dysfunction: Multi-level study based on hormone receptor responses

Ying Ren,Yue Wang,Yang Wang,Xia Ning,Guangke Li,Nan Sang

Oxygenated polycyclic aromatic hydrocarbons (OPAHs) are a class of emerging environmental contaminants that exhibit high toxicity compared to parent PAHs. In addition to carcinogenic, teratogenic and mutagenic effects, recent studies show their potential to cause endocrine disruption, but the reports are controversial. In this study, we employed hormone receptors (ERα/AR/GRα/TRβ)-mediated dual luciferase reporter gene assay and molecular docking, and found that five typical OPAHs exhibited agonistic activity towards hormone receptors, and hydrogen bonding and hydrophobic interactions are the primary binding forces involved in OPAHs-receptor interactions. Then, we developed a weighted scoring system coupled with computerized screening and clarified that 1,2-benzanthraquinone (BAQ) had the strongest hormonal effects, while anthraquinone (AQ) exhibited the weakest effects. Using the in vivo exposure-response model, we clarified that BAQ induced hormone receptor-coupled developmental toxicity in zebrafish larvae, evidenced by increased expression of androgen receptors and key genes involved in hormone synthesis, pericardial edema, and reduced body length. Importantly, we successfully constructed androgen response element-enhanced green fluorescent protein (ARE-EGFP) transient transfection zebrafish embryos, and confirmed the androgenic potency of BAQ, but not AQ. These findings highlight the endocrine-disrupting effects in the risk management of OPAHs.