DEHP暴露对雄性斑马鱼生殖及子代发育影响的DNA甲基化机制研究

邻苯二甲酸二乙基己酯（di-(2-ethylhexyl)-phthalate, DEHP）作为增塑剂广泛用于食品包装、医疗用品、汽车产品及儿童玩具等的制造，在环境中普遍存在。目前在各种环境介质、野生动物体内以及人体各种组织中均检测出它的存在。已有的研究表明DEHP对雄性动物具有生殖毒性，但是对子代发育的影响及其分子机理，目前尚不明确。鉴于上述原因，在本项目中，我们将以雄性斑马鱼为模型开展DEHP环境相关浓度的长期暴露，综合运用环境毒理学和分子生物学技术，从基因、蛋白、激素和组织病理学水平，研究DEHP对雄性斑马鱼的生殖毒性及对子代发育影响。检测性腺组织和子代DNA甲基化水平，分析关键基因启动子区域CpG岛甲基化修饰情况，揭示其毒性作用分子机理。本研究的开展将会拓展人们对DEHP毒性机制的认识，为其它有机污染物的毒性机理评价提供新的思路。

Di-(2-ethylhexyl)-phthalate (DEHP) is extensively used as plasticizer in consumer products, such as food packaging, medical devices, car products and children's toys. It has been detected in a variety of environmental media as well as wild animals and human tissues. Previous studies indicated that DEHP affected reproductive system on male animals, but the effect on offspring development and the molecular mechanism underlying this process have not yet been clarified. Therefore, in this proposal, we will study the effects of long-time DEHP exposure on male zebrafish production with environmentally relevant concentrations, and the following impacts on offspring development. With the environmental toxicology and molecular biology techniques, we will comprehensively evaluate the results on gene expression, hormone concentration and histopathology. In order to get a better understanding of the mechanism, we will analyze the changes of DNA methylation on testis and offspring, then the status of methylation on CpG islands in several key genes will also be detected. This study will give us a new insight on DEHP-mediated toxicity mechanism and provide novel ideas on studying toxicity of other organic pollutants.