酚类环境雌激素在子宫肌瘤发生发展中的作用和分子机制研究

酚类环境雌激素的环境污染日趋严重，小样本流行病学调研显示其与子宫肌瘤的发病密切相关，但其在子宫肌瘤发生发展中的确切功能和分子机制目前仍不清楚。本研究在前期环境危险因素调查及易感生物标志研究的基础上，以大样本人群为研究对象，结合内暴露和外暴露深入调查分析酚类环境雌激素与子宫肌瘤发病风险的相关性；同时开展酚类环境雌激素相关合成及代谢酶基因多态性研究，从而明确酚类环境雌激素在子宫肌瘤发生发展中的作用和分子机制；构建原代子宫肌瘤细胞模型，研究酚类环境雌激素在子宫肌瘤发生发展中的功能，并结合RNA-seq和ChIP-seq技术，在全基因组水平检测酚类环境雌激素在子宫肌瘤细胞中引起的基因表达和组蛋白修饰的改变，绘制酚类环境雌激素诱发子宫肌瘤细胞遗传及表观遗传变异图谱，分析关键信号通路的影响，筛选敏感的生物标志和药物靶点，为指导环境干预和子宫肌瘤的防治提供理论依据。

The pollution of phenolic environmental estrogens is increasingly serious. Small sample epidemiological surveys have revealed their relationship with uterine fibroids. Yet the exact function and molecular mechanism in the development of uterine fibroids remain unclear. On the basis of previous investigation of environmental risk factors and susceptibility biomarker research, this study, focusing on large sample population as the research object and combining internal and external exposure, aims at looking into and analyzing the correlation between phenolic environmental estrogens and uterine fibroids risks. Meanwhile, a polymorphic study on the enzymes involved in the synthesis and metabolism of phenolic environmental estrogens is carried out in order to define the effect and molecular mechanisms of environmental estrogens. Furthermore, by reaching on the effect of phenolic environmental estrogens in the development of uterine fibroids via established uterine fibroid cells model, with the help of RNA-seq and ChIP-seq technologies, the alterations of gene expression pattern and histone modification in uterine fibroid cells caused by phenolic environmental estrogens are detected; The map of uterine fibroid cell genetic and epigenetic variation induced by phenolic environmental estrogen is created in order to analyze the effect of.critical signaling pathways, which helps to screen sensitive biomarkers and medication targets so as to provide theoretical bases for the environmental intervention as well as the prevention of uterine fibroids occurrence.