Disruption of zebrafish sex differentiation by emerging contaminants hexafluoropropylene oxides at environmental concentrations via antagonizing androgen receptor pathways

• DOI: 10.1016/j.envint.2024.108868
• Publication Date: 2024-07-02T22:25:57Z
• Authors: Tingyu Lu; Wei Zheng; Fanglin Hu; Xicha Lin; Ran Tao; Minjie Li; Liang-Hong Guo
• Keywords: Perfluorooctanoic acid; Docking (animal); Sexual Differentiation

As alternatives of perfluorooctanoic acid (PFOA), hexafluoropropylene oxide dimeric (HFPO-DA) and trimeric (HFPO-TA) have been detected increasingly in environmental media even humans. They shown to exhibit reproductive toxicity model species, but their effects on human remain unclear due the knowledge gap mode action. Herein, (anti-)androgenic two HFPOs PFOA were investigated underlying toxicological mechanism was explored by combining zebrafish test, cell assay molecular docking simulation. Exposure juvenile chemicals during sex differentiation promoted feminization, with HFPO-TA acting at an concentration 1 μg/L. The inhibited proliferation prostate cells transcriptional activity androgen receptors (AR), displaying strongest potency. Molecular revealed that bind AR a conformation similar known antagonist. Combined vivo, vitro silico results demonstrated disrupted likely antagonizing AR-mediated pathways, provided more evidence is not safe alternative PFOA.