环境激素暴露是男性生殖健康受损的重要因素。典型环境激素p,p’-DDE是有机氯农药DDT在环境和生物体内最持久、浓度最高的代谢产物，具有跨代雄性生殖毒性，分子机制不明确。本研究通过横向（对照、p,p’-DDE组和叶酸干预组）和纵向（F1代、F2代和F3代）比较，采用MeDIP-Seq、MeDIP-qPCR、亚硫酸氢钠测序、全基因组表达芯片等方法，分析F0代孕鼠p,p’-DDE暴露致雄性F1-F3代成熟精子、支持细胞基因组印记缺陷、表达改变及甲基供体叶酸的干预效应，分析甲基化修饰与基因表达改变、生殖细胞与体细胞印记改变之间的关系，探讨基因组印记在p,p’-DDE致跨代雄性生殖毒性中可能机制。本研究从表观遗传学层面阐明p,p’-DDE暴露出生子代风险增加的原因及可能阻断途径，为有机氯污染物致雄性生殖毒性防治开拓思路，并为其他环境激素的表观遗传效应及复杂疾病的宫内源性研究提供新的理论依据。

Environmental hormones exposures are important factors with adverse effects on male reproductive function. p,p’-Dichlorodiphenoxydichloroethylene (p,p’-DDE) is the primary metabolite of organochlorine pesticide DDT with strong persistence. It is also a kind of typical environmental hormones found in environment and organism. p,p’-DDE could induce transgenerational male reproductive toxicity. However, the exact mechanism is still unclear. This study will analyze the possible mechanism of genomic imprinting in the transgenerational male reproductive toxicity. With the method of methylated DNA immunoprecipitation sequencing, methylated DNA immunoprecipitation qualitative PCR, bisulfite sequencing PCR and genome-wide microarray analyses, we will explore the effect of p,p’-DDE on the epigenetic transgenerational inheritance of altered transcriptome and epigenome of Sertoli cell and sperm and the possible interventional effect of folic acid. After horizontal and vertical comparison, we will analyze the relationship between methylated modification and gene expression, and explore the effect of altered germline imprinting on the somatic cells. From the perspective of epigenetics, this study will demonstrate the possible mechanism underlying male reproductive impairment induced by p,p’-DDE exposure and the possible interventional method. This study will provide new theory basis for the altered epigenetic effect induced by other environmental chemicals and the intrauterine source of chronic diseases.