早期自然流产是妊娠严重并发症，给妇女的身心带来了巨大负面影响，甚至面临生育困难。表观遗传在着床前后的早期胚胎发育中发挥着重要的调控作用。我们的前期研究发现：印记基因H19甲基化异常可能导致人种植前胚胎质量低下，PEG1、H19、LIT1等印记基因甲基化程度改变、甲基化转移酶3A基因启动子区单核苷酸多态性（SNP）可能与早期自然流产的发生相关。本项目拟采用分子生物学技术从不同时期、不同类型停止发育的人类早孕绒毛组织的甲基化与去甲基化动态变化的角度，研究5-甲基胞嘧啶(5-mC)与5-羟甲基胞嘧啶(5-hmC)在人类绒毛组织中全基因组的变化模式，研究其含量与主动去甲基化酶TET1，TET2，TET3的RNA表达变化的相关性，最后验证绒毛组织中确有TET蛋白的存在。探索去甲基化异常在早期自然流产中的作用和机制，为自然流产的病因和防治提供表观遗传学依据。

Early pregnncy loss (EPL) is a major complication of early pregnancy and has serious impacts on women with an increased possibility of second infertility. The global DNA epigenetic profile of the genome is dynamically reprogrammed during embryogenesis and the early development of the fetus. In previous observations, we reported abnormal methylation of H19 DMR was related to poor quality of embryos and the Methylation pattern of imprinted genes may contribute to EPL, such as PEG1,H19 and LIT1. The DNMT3A polymorphism is a novel functional single nucleotide polymorphism(SNP )and contributes to its genetic susceptibility to pregnancy loss. In the current study ,we will investigate dynamic of5-methylcytosine（5-mc）and 5-hydroxymethylcytosine (5-hmc)in human chorionic villi from first trimester pregnancy. RNA levels of Ten-eleventranslocation (TET) protein will be tested, and TET protein also will be verified the presence in human chorionic villi. The findings of the current study would provide new insights into the effect and mechanism of demethylation on EPL. The epigenetic etiology would be explored for prevention and treatment in future.