尿道下裂是小儿最常见的泌尿生殖道先天畸形之一，发病率逐年上升。课题组前期研究发现环境内分泌干扰物DEHP（一种增塑剂）可导致动物尿道下裂，而维生素E能够有效拮抗尿道下裂发生，其机制尚不清楚。本项目拟在前期系列研究基础上，针对处于发育关键期的胎鼠尿道板上皮细胞，从尿道发育动力学角度（细胞凋亡、细胞迁移、上皮-间质转化）以及基因、蛋白表达等多方面，深入探讨尿道发育形成过程及其基因调控机制；进一步采用比较基因组与蛋白组学、表观遗传学、毒理学等方法探索尿道下裂动物模型其尿道板上皮细胞形态、功能等异常与相关基因、蛋白的关系，揭示尿道下裂发生机制；最终旨在探究维生素E预防尿道下裂发生机制，完善其安全性评估。本研究必将为临床预防生殖畸形的发生提供科学的实验依据。

Hypospadias is one of the most common congenital genitourinary malformation of children, its incidence is increasing year by year. In our previous work, we found that DEHP (a sort of plasticiser) which acts as an environmental endocrine disruptor can induce animal hypospadias, and vitamin E can effectively resist the toxicity. However, the mechanism is not clear. Based on our previous research work, we planning to investigate the mechanism of urethral formation and its genetic regulation. Focusing on the epithelium of fetal urethral plate in key developmental period, the research work of this project includs developmental dynamics of urethra (cellular apoptosis,migration and epithelial mesenchymal transformation) and the genetic and protein expressions. By using comparative genomics and proteomic, epigenetics and toxicology et al methods, the cellular morphology, function of urethral plate of hypospadic animal model and the relationship with particular genes and proteins will be explored. The ultimate aim is verifying the mechanism of preventive and side effects of vitamin E on hypospadic rat. We are certain that this work will provide experimental evidence for clinical prevetion of genitourinary malformation.