胚胎植入是决定妊娠是否成功的关键环节。雌孕激素在该过程中发挥关键作用，雌孕激素作用于子宫内膜多种细胞，通过其核受体和局部产生的其他因子组成复杂网络共同调控胚胎植入的发生。但该网络在转录、转录后和翻译等水平的稳态调控还不清晰。RNA的m6A甲基化修饰是近年来发现的可在多个水平影响基因表达的新型核酸修饰，其在围植入期子宫内膜中的功能还未知，本研究提出关键科学问题“Mettl14介导的RNA m6A修饰在调控胚胎植入和蜕膜发育过程中的功能机制是什么？”，拟利用在体子宫细胞特异敲除动物模型，结合临床样本和体外内膜细胞培养、生化分子等技术手段，系统研究：1）m6A以及参与m6A修饰和识别的各类分子在围植入期子宫内膜中的动态表达模式；2）m6A甲基转移酶Mettl14在子宫内膜容受性建立过程中的功能；3）Mettl14对蜕膜发育的调控作用；4）Mettl14在围植入期子宫功能发挥中的作用机制。

Embryo implantation and decidualization are critical for the success of pregnancy, which are precisely regulated by ovarian estrogen and progesterone, as well as locally produced signaling molecules at the maternal-fetal interface. Through some molecule have been proven to be important for these process, how the various signaling molecules are regulated at the transcriptional, post-transcriptional and translational level remain still elusive. m6A RNA methylation was a recently discovered RNA modification and regulate gene expression at various level, which are likely to be potential vital players during early pregnancy. To address how these RNA modification event participants in the early pregnancy, multiple genetic mouse models, combined with the human endometrial sample, in vitro cultured endometrial cells, and biochemical approached to investigate: 1) the spatiotemporal expression pattern of m6A and related modification enzymes, readers, in the periimplantation uterus; 2)the physiological role of Mettl14 mediated m6A methylation during uterine receptivity establishment; 3) the involvement of Mettl14 for uterine stroma decidualization; 4) the molecular mechanism for Mettl14’s function during the periimplantation stage.Based on these researches, we believed that it will provide a more comprehensive description for embryo implantation at the epi-transcriptional level, and give some clues to better understanding the recurrent implantation failure and spontaneous abortion in humans.