典型POPs污染区对鸟类的胚胎毒性及基于AhR活性筛选关键致毒物质

There is globally widespread concern that many persistent organic pollutants in environmental have pose potential health risk to wildlife. Birds are widespread and provide important function in ecosystem. However, little is known about the toxicity and ecological risk of avian species when exposed to mixture of organic pollutants, lack of knowledge especially molecular mechanism of toxicity. Although previous studies have reported that organic pollutants in the electronic recycling waste (e-waste) site might play an important factor in decline of bird populations, does the combined pollution of organics could lead to embryo toxicity of birds from this area? How about the embryo toxicity effect of birds? Is AhR activation important to the embryo toxicity? All of those need further research. Therefore, we plan study the embryo toxicity effect to birds from e-waste area by injecting organic extracts of eggs from local birds; to elucidate the influence of AhR activation to molecular mechanism in embryo toxicity when exposure to combined organics pollution; to screen and identify key toxic chemicals by integrating in vitro toxicity test method (LRGI-AhR) and effect-directed analysis (EDA). This project will help us assess the embryo toxicity correctly, improve the understanding to avian AhR-AOP, and provide science support for government make management policies.

环境中持久性有机污染物（POPs）在野生动物的累积及其危害已引起关注，鸟类具有重要的生态功能，但现有报道缺乏POPs对鸟类的毒性和生态危害的研究。研究发现电子垃圾拆解区的POPs与当地的鸟类种群数量减少相关，POPs复合污染是否会导致鸟类的胚胎毒性？基于AhR介导的有害结局路径（AOP）为研究新型污染物的作用模式及毒性预测提供了指导性框架，评估AhR激活在POPs复合污染中的致毒作用可以完善AhR-AOP；POPs复合污染中是否存在新型致毒污染物都亟需进一步研究。本项目拟萃取该典型污染区鸟蛋的POPs，进行体内（胚胎注射）测试和体外（LRGI - AhR）测试评估环境POPs的混合暴露对鸟类的胚胎毒性及生态风险，并研究AhR激活对毒性效应的影响；利用LRGI-AhR和基于效应的污染物识别（EDA）筛选关键致毒组分。本项目的完成可以为正确评价其生态风险和制定相关管理政策提供重要依据。

持久性有机污染物（POPs）在野生动物的累积及其危害引起广泛关注，已有研究发现典型POPs污染区（电子垃圾拆解区）有机污染暴露与当地鸟类种群数量减少相关，复合暴露是否会导致当地鸟类的胚胎毒性？其毒性效应与致毒机制均需进一步研究。. 针对真实环境的有机污染物混合暴露，本研究选择典型电子垃圾拆解区（清远和贵屿）的野生鸟类为研究对象，（1）利用荧光报告基因法（大鼠H4IIE-luc法和鸡AhR1-LRG法）评价鸟类生物萃取物的AhR活性，综合化学分析评估其胚胎毒性相关的生态风险；（2）选取高AhR活性样品，通过胚胎暴露实验研究其胚胎毒性；（3）通过转录组研究其潜在致毒分子机制。主要研究结果如下：. （1）AhR受体报告基因法和化学分析均发现两地鸟类生物萃取物具有潜在生态风险。两地样品均具有AhR活性，鸡AhR1-LRG法测得生物毒性当量范围为9.30E+06-5.57E+08 pg TCDD/g 脂重；肝脏中检测到高PCBs（240.5 ng/g湿重-2105 ng/g湿重）和PBDEs浓度（557.7 ng/g湿重-4870 ng/g湿重）。化学分析法评估的风险远低于鸡AhR1-LRG法，表明鸟体内可能存在其他未知污染物。. （2）高AhR活性的生物萃取物对鸟类胚胎有显著的胚胎毒性，能导致显著的胚胎致死效应，抑制雏鸡的生长，造成肝脏、骨骼等器官发育异常。胚胎半致死效应浓度和与AhR活性间存在正相关性，表明基于鸡AhR1-LRG测试可用于评估环境复合污染物对鸟类的胚胎毒性。. （3）转录组分析发现生物萃取液可显著激活雏鸡胚胎AhR信号通路，诱导CYP1A2、GSTA2、UGT1A1等基因表达，主要通过影响AhR调控的类固醇激素合成、PPAR信号通路和细胞色素P450调控的外源物质代谢通路对鸟类胚胎产生毒性。. 研究结果为真实环境中POPs混合暴露对野生鸟类的生态毒性评价提供了理论依据与技术支撑。