mmu-miR-100家族通过调控mTOR等增殖相关基因对小鼠子宫内膜基质细胞增殖及胚胎着床的影响

胚胎着床是哺乳动物生殖的重要过程，其机制涉及胚胎与母体之间复杂而精细的多因素协同作用，但具体机制尚不明确。在胚胎着床过程中，子宫内膜细胞有控性增殖及分化是决定妊娠成功与否的关键之一；而miRNAs在细胞增殖、分化调控中起着重要作用。本课题组前期研究发现，在小鼠胚胎着床窗口期前后子宫内膜中一些miRNAs明显差异表达，以mmu-miR-100家族尤为明显。经靶基因预测及基因功能分类，发现miR-100家族指向的靶基因mTOR ,FGFR3等多与细胞增殖及分化调控相关。为此，本课题拟用妊娠小鼠模型、siRNA技术、基因转染等方法结合体内外实验，对miR-100家族及其增殖、分化相关的多个靶基因mTOR ,FGFR3等在小鼠子宫内膜中的生物学功能及在胚胎着床过程中的作用机制进行研究；为研究子宫内膜细胞增殖、分化异常所致不孕、流产等疾病打下理论基础，并为基于miRNAs的助孕治疗手段提供新的思路。

Embryo implantation ,an important process of human and mammalian reproduction, involved in the interaction between maternal endometrium and embryo through the multiple molecules and signalling cascades. While the mechanism is still unclear.The current study shows that during the process of embryo implantation, the fine regulation of cell proliferation in maternal endometrial is one of the key factors for the successful pregnancy. while miRNAs play an important role in regulation of cell proliferation . Through the studies of the pregnant mouse model, our research found that the expression of miRNAs is significant different in endometrial before and after ‘implantation window’,especially the mmu-miR-100 , an important role in the regulation of cell proliferation . So we would like to use pregnant mouse model, siRNA technology, gene transfection , genes reporter etal ,combine with the in vivo and in vitro experiment, to analysis the biological function , molecule mechanism,and effect to implantation of mmu-miR-100 and multiple target genes related to proliferation in endometrium on early pregnancy mouse model. Through the research we can establish the experimental basis for studying the failure of infertility, miscarriage and endometriosis disease ,which leading by the regulation of endometrial cell proliferation contriled by miRNAs ,seak for new means basis to miRNAs to control reproductive.