胚泡着床和胎盘形成是妊娠建立和维持的关键环节，并与滋养细胞的增殖和侵袭功能密切相关。前期研究表明，MNSFβ蛋白功能的缺失会导致小鼠胚胎着床异常而引发早期流产，唯其作用机制尚不明。已有报道，p53和p27参与调控滋养细胞的增殖和侵袭活性，而p27/CCND2/CDK4途径参与调控肿瘤细胞的增殖和侵袭；我们发现，MNSFβ功能缺失会导致孕早期小鼠母胎界面p53、p27、CCND2和CDK4等基因表达水平的异常变化，并推测MNSFβ可能通过p53/p27/CCND2/CDK4途径调控滋养细胞的增殖和/或侵袭活性。为此，本项目拟利用HTR8/SVneo细胞模型，观察MNSFβ表达水平的变化对人滋养细胞增殖和侵袭能力，以及p53/p27/CCND2/CDK4途径中各分子表达水平的影响；同时，建立胎盘特异性MNSFβ基因剔除小鼠模型，在体研究分析MNSFβ缺失对胚胎着床和胎盘形成的影响及其分子机制。

Embryo implantation and placentation, two critical events during the establishment and maintenance of pregnancy, are dependent on the appropriate proliferation and invasion of trophoblast cells. Our previous works demonstrated that the dysfunction of MNSFβ could disrupt the implantation process and lead to the early pregnancy loss in mice, but the underlying mechanisms are still unclear. It has been reported that, p53 and p27 participate in regulation of proliferation and invasion of trophoblast cells, and the p27/CCND2/CDK4 pathway is involved in the proliferation and invasion of tumor cells. We also observed that, the alteration in MNSFβ expression level at the maternal-fetal interface was associated with the expression pattern alteration of p53、p27、CCND2 and CDK4. Thus, we hypothesized that, MNSFβ might regulate the proliferation and invasion of trophoblast cells via p53/p27/CCND2/CDK4 pathway. The present study will carry out to investigate the effects of up- or down-regulated intercellular MNSFβ expression on the proliferation and invasion of HTR8/SVneo cells in vitro; and to establish the placenta-specific MNSFβ gene knockout mouse model to explore the roles of MNSFβ played in the processes of implantation and placentation in mice in vivo.