内质网应激在TDCIPP致土著鲫鱼胚胎发育毒性中的作用及调控机制

磷酸三（1，3-二氯异丙基）酯（TDCIPP）是一种新型环境污染物，研究表明它能够引起多种毒性，其中胚胎发育毒性是典型的毒性效应之一。最近，我们发现内质网应激（ERS）是TDCIPP多种毒性效应的上游机制，且也参与了胚胎发育毒性。然而我们对ERS在TDCIPP诱导的胚胎发育毒性中的功能角色和调控机制还知之甚少。本项目以土著鲫鱼为模型，开展环境相关剂量TDCIPP的长期暴露实验，暴露结束后人工授精方法收集胚胎，运用共聚焦显微成像、透射电镜成像、显微注射和蛋白质组学等分子生物学技术研究ERS介导的TDCIPP胚胎发育毒性和分子机制。在前期研究的基础上，我们将重点关注细胞层面上的外包抑制效应、ERS激活和ERS下游4种致毒信号通路（氧化损伤，发炎反应，细胞凋亡和蛋白质翻译抑制）的生物学反应。本项目将从新的视角阐明TDCIPP胚胎发育毒性的分子机制，为TDCIPP的风险评价和风险管理提供数据支撑。

Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is an emerging environmental pollutant, and accumulated evidences have demonstrated that TDCIPP can cause multi-toxic effects, and the embryonic developmental toxicity is typical one. Recently, we have found that endoplasmic reticulum stress (ERS) is involved in upstream mechanisms of TDCIPP-induced toxicities, and is also responsible for embryonic developmental toxicity. However, the role and regulation of ERS in TDCIPP-induced embryonic developmental toxicity remains unexplored. In this project, using aboiiginal crucian carp (Carassius carassius) as an animal model, a long-term exposure experiment with environmentally relevant concentrations of TDCIPP will be performed. After exposure, fish embryos will be collected by artificial insemination method. We will examine ERS mediated embryonic developmental toxicity of TDCIPP and explore related molecular mechanisms by using confocal microscopy imaging, transmission electron microscope imaging, microinjection, proteomics, and other molecular biological technologies. Based on our previous studies, we will focus on cell-level inhibition effect on epiboly, ERS activation and biological response of four toxicity-related signal pathways in ERS downstream. Our results will elucidate the molecular mechanisms of embryonic developmental toxicity of TDCIPP in a new prospective, and provide statistical supporting for risk assessment and management of TDCIPP.