有机磷酸酯（OPEs）作为一类与生殖疾病相关的新兴污染物，流行病学调查和动物实验都显示OPEs能够引起精子毒性。但目前对于OPEs诱发精子毒性的机制研究还非常缺乏。本项目拟选取OPEs类污染物为目标化合物，以体内与精子发生和精子能动性密切相关的脂肪酸酰胺水解酶（FAAH）为研究靶点，拟在分子、细胞及动物水平考察OPEs对FAAH活性（包括酶催化活性、酶蛋白调控基因表达和催化底物大麻素含量）的毒性作用，揭示其毒性作用规律。从酶活性、细胞凋亡和生物效应等多个角度全面研究OPEs对精子发生的干扰效应，进而明确FAAH在OPEs诱发精子毒性中的作用及机制。对不同结构OPEs与FAAH结合进行分子模拟，阐明OPEs干扰FAAH酶活的结构基础。该项目可揭示OPEs诱发精子毒性的新型分子机制，为全面评价OPEs的健康风险提供科学线索和依据。

Organophosphate esters (OPEs), as a new class of emerging organic pollutants, have been confirmed to be associated with reproductive disease. Epidemiologic studies and animal experiments have showed that the OPEs could lead to spermatotoxicity. However, the mechanism of OPEs’ spermatotoxicity is still unknown. The fatty acid amide hydrolase (FAAH) plays curcial roles in spermatogenesis and sperm motility. In the present study, we will investigate the interference effect of OPEs on the FAAH catalytic activity, gene expression regulated by enzyme protein and the content of catalytic substrate anandamide at molecular, cellular and animal levels, revealing the laws of its toxic effect on FAAH. The disruption effect and mechanism of OPEs on spermatogenesis via FAAH mediated will be systematically studied through the enzymatic activity, cell apoptosis and physiological functions. In order to identify the molecular basis and structural determinants, the OPEs-FAAH binding model will be studied by computational docking method. This proposal will make clear the function of FAAH in the OPEs induced spermatogenesis disruption, and will provide experimental evidence and theoretical basis for environmental risk assessment of OPEs.