P62/SQSTM1介导自噬-染色质泛素化缺陷在老化态纳米ZnO致雌性生殖细胞遗传毒性中的调控机制

纳米氧化锌因其独特理化性质在实现大规模生产与应用的同时，将不可避免地进入并聚集于水环境，且随时间推移发生系列物化特性转化行为（老化），使其诱发的健康损害结局显著有别于“原始态”。而这种转化行为引发雌性生殖细胞遗传毒性效应及相关机制研究仍旧较为匮乏。基于前期研究的基础，本项目综合考虑纳米氧化锌在水环境中的时空转变过程，对比原始态纳米氧化锌，探究老化态材料对自噬缺陷标志蛋白P62/SQSTM1结构与功能的影响，阐明纳米氧化锌水体老化过程中与关键蛋白P62/SQSTM1的相互作用在细胞自噬-染色质泛素化缺陷-DNA损伤与修复调控网络中的关键作用机制，以期为精准化干预水环境中ZnO NPs诱导的雌性生殖器官病变以及不孕症提供理论依据。

Zinc oxide nanoparticles (ZnO NPs) as typical metal oxide nanoparticles are being produced abundantly and applied increasingly in various fields. In the environment, the unique properties of ZnO NPs make them incline to undergo physicochemical transformation over time (aging), driving ZnO NPs away from their pristine state, which in turn modify their environmental health and safety. However, the underlying mechanisms involved in the genotoxicity of female germ line induced by ZnO NPs during aging process are still unknown. Based on the previous studies, the main objectives of current project were to investigate the adverse effects of autophagy deficiency biomarker-P62/SQSTM1 after treatment with ZnO NPs in aquatic environments during aging process, and then gain more insight into the underlying mechanism involved in the key role of p62/SQSTM1 on autophagy-chromatin ubiquitination-DNA damage. This project will provide a basis for the safe application of ZnO NPs and prevention related disease.