流行病学调查发现环境污染物多氯联苯(polychlorinated biphenyls，PCBs)已经威胁到了人类的生殖和繁衍，我们和他人的研究均证实PCBs对亲代小鼠可产生明显的生殖毒性，并且可导致生殖毒性的跨代传递，最近我们研究还发现PCBs可导致子代小鼠卵母细胞印迹基因Snrpn DMR甲基化水平的改变。目前尚不了解PCBs造成生殖毒性跨代传递的表观遗传学机制。本研究以PCBs的典型代表物PCB118作为染毒物质，制备三类染毒模型，获得F1到F3代小鼠。选取与PCBs生殖毒性具有相关性的5个印迹基因，利用分子生物学技术,重点研究PCB118对小鼠生殖细胞中这5个印迹基因的表达和DMR甲基化水平的影响及其机制，初步探索PCBs生殖毒性的跨代传递与生殖细胞中印迹基因DNA甲基化之间的相关性，为由环境污染物引起的不孕不育和出生缺陷的预防和治疗奠定基础。

Epidemiological investigation showed that PCBs (polychlorinated biphenyls), one species of environmental pollutants, had been a threat to human reproduction. Studies on animals had proved that PCBs not only have a significant reproductive toxicity on parental mice, but also can be inherited trans-generationally. Furthermore, our recent study proved that DMR methylation patterns of imprinted genes Snrpn in oocytes of offspring mice had been altered by PCBs exposure. However, it is still unclear about the epigenetic mechanism underlying trans-generational inheritance of reproductive toxicity caused by PCBs exposure. PCB118, a typical PCB, is used in this study to build three PCB exposure models which are in the period of mouse pre-gestation, gestation and lactation respectively, and then get F1, F2 and F3 offspring mice. Five imprinted genes Peg3, Snrpn, H19, Igf2 and Igf2r, which are related to reproductive toxicity in germ cells, were chosen, and molecular biological technique was utilized to analyse their methylated states of differentially methylated regions (DMRs) in mouse gametes (F0 to F3) and the expression of relevant proteins in order to understand the molecular mechanisms. This study aims to illustrate the correlation between the effects of trans-generational inheritance of reproductive toxicity and DNA methylation of imprinted gene in gametes, and to provide molecular understanding for prevention and treatment of infertility and birth defects caused by environmental pollutants.