邻苯二甲酸酯侧链长度与雄性生殖毒性的相关性及分子机制研究

邻苯二甲酸酯类化合物（PAEs）已成为一种环境中广泛存在的具有内分泌干扰作用的有机污染物，人群的普遍暴露及其健康效应，包括对男性生殖健康的影响，已越来越被公众和学术界关注。基于不同类型PAEs的侧链结构多样性、代谢的差异以及对男性生殖健康的不同影响，我们提出PAEs的侧链长短与毒性相关的假说：PAEs侧链长度是其通过氧化应激和干扰内固醇类性激素分泌影响雄性生殖健康的关键因素。本项目拟利用小鼠睾丸间质细胞模型，采用不同侧链长度的PAEs进行暴露，通过分析PAEs代谢、氧化应激、表观遗传修饰、 类固醇性激素分泌，研究不同类型PAEs的毒性差异，认知PAEs结构形态与其毒性的相关性，为阐明PAEs的男性生殖毒理提供参考，为安全合理利用PAEs提供科学依据。

Phthalate esters (PAEs) are widely distributed environmental pollutants. They have been identified as endocrine-disrupting chemicals. Human exposure to PAEs has been linked to the adverse effects of reproduction,child development and metabolic disturbance. Their impairment of male reporduction have been concerned as a public health problem. Because of the fact that PAEs is a family chemicals with the same phthalic acid but the different carbon side-chains,PAEs show much diversity in their metabolic processes(e.g.,hydrolysis and oxidation)in human body.Their male reproductive toxicity are also discrepant. We hypothesize that PAEs side chains are associated with their specific toxicity, and the lengthes of the side chains may play the key roles in oxidative stress, sexual steroid hormone disruption, and sexual organ development. In this study, we intend to explore the toxicology differences of the different PAEs by using Leydig cell model. The detoxification from oxidation stress, DNA methylation for genetic regulation and sterogenesis will be investigated. The study will help us understand PAEs' structure-activity relationship, improve our knowledge of their reproductive toxicology and provide reliable scientific reference on the safe and rational use of PAEs in our daily life.