DNA甲基化是基因表达最常见的表观遗传调控方式，在胚胎围植入期子宫内膜的发育和分化中可能扮演重要角色。我们近期研究显示：DNA甲基转移酶（Dnmt）在胚胎植入过程中呈现规律性表达；Dnmt抑制剂或甲基供体叶酸的缺乏都可诱导Dnmt表达异常而致胚胎植入障碍。但Dnmt通过调控哪些胚胎植入关键基因的甲基化水平和表达而影响胚胎植入，目前仍不清楚。因此，本研究拟利用loxP-PRcre系统构建Dnmt1、Dnmt3a和Dnmt3b条件性敲除小鼠模型，采用RRBS和DGE联合分析方法，探索Dnmt单敲或双敲除后对胚胎植入关键基因的甲基化影响。并在此基础上，进一步分析这些胚胎植入关键基因DNA甲基化改变对其下游基因表达的调控作用以及对子宫内膜容受性建立、内膜细胞的增殖与分化以及血管形成的影响，从而阐明Dnmt在胚胎围植入期的甲基化调控作用及其机制，为寻求新的生殖调控手段及不孕症的诊治提供新的思路。

DNA methylation is the most common epigenetic regulation of gene expression, may play an important role in the endometrium development and differentiation during peri implantation. Our recent study shows: DNA methyltransferase (Dnmt) show the regular expression in the endometrium dring implantation. Dnmt inhibitor or the lack of methylation donator such as folic acid can induce the anomal expression of Dnmt and embryo implantation disorder. However, it still remains to be unknown of the target genes by which Dnmt controls their level of methylation and expression thus affecting embryo implantation. This study intends to builds Dnmt1, Dnmt3a and Dnmt3b conditional knockout mice model using loxP-PRcre system. Using RRBS and DGE conjoint analysis,exploring the effect of single or double knockout of Dnmts on key gene methylation for embryo implantation. And on this basis,further analyzing its regulation on the downstream genes relating to the endometrial receptivity establishment, endometrial proliferation and differentiation as well as the vascular formation. By this study, we may well find the role and regulating mechanism of Dnmt in implantation and provide a new way for the reproductive control as well as diagnosis and treatment of infertility.