人类和动物的生活环境，尤其水源和食品，受到了环境类雌激素等内分泌干扰物的广泛污染，严重损害了人类和动物的生殖力，诱发不孕不育。邻苯二甲酸二(2-乙基）己酯（DEHP）是水源中广泛存在的雌激素类似物。本项目组前期研究发现，DEHP暴露经妊娠母体危害胎儿卵母细胞早期发生和减数分裂启动，但其机制尚不明确。本项目以前期的DEHP毒害胎儿卵原细胞减数分裂启动的单细胞转录组研究结果为基础，借助ATAC-seq技术从染色质动态结构变化角度揭示DEHP暴露诱发卵母细胞发育毒性的机制，并结合组蛋白ChIP-seq分析阐明DEHP暴露经“组蛋白修饰改变—染色质开放—转录表达开启”关系网络对卵原细胞减数分裂启动产生毒害作用的发生途径，系统阐述DEHP暴露毒害雌性生殖力的表观遗传机制。该研究将为解决环境类雌激素诱发雌性生殖力下降这一难题提供了坚实的理论基础，为维持雌性生育力提供有益的理论借鉴。

The environment for human and animals, especially water and food, has been extensively contaminated by endocrine disruptor chemicals such as environmental estrogens, which seriously harm the reproductive capacity and cause reproductive disorders. Di (2-ethylhexyl) phthalate (DEHP), one kind of environmental estrogens, is found in drinking water widely to damage human and animal reproductive capability. Our previously results have demonstrated maternal DEHP exposure disrupting fetal oogenesis and meiotic initiation. However, the underlying mechanisms are poorly understood. In this investigation, based on our previous single cell RNA-seq data of DEHP exposure impairing fetal oogonia meiotic initiation, we will explore the underlying mechanisms of maternal DEHP exposure on fetal oogenesis from the perspective of dynamic structural changes of chromatin using the ATAC-seq technology. In addition, combined with histone ChIP-seq analysis, this project will investigate the mechanisms of DEHP disrupting fetal oogenesis through “histone modification change-chromatin opening-transcription expression” pathways. Furthermore, the epigenetic mechanisms of DEHP exposure on female reproductive capability will be elucidated systematically. The findings of this proposed project will provide a solid theoretical basis for solving the problem of environmental estrogens caused female reproductive disorders, and a beneficial and theoretical guide to improve human and animal reproductive performance.