ALK5在胚胎着床中的作用及调控子宫内膜基质细胞蜕膜化的机制研究

ALK5 (Activin receptor-like kinase 5) is a main subtype receptor of TGF-β1. It is shown that ALK5 was highly expressed during the period of embryo implantation both in mice and human endometrial tissue. Moreover, ALK5 is increasing with the process of decidualization in stroma cells in vitro study. It is also shown that decidualization cannot be preceded, and p21 is also dramatically down expressed, after the use of ALK5 siRNA. Thus we put forward a hypothesis that ALK5 may be involved in the regulation of embryo implantation via regulating decidualization. In this study, we intent to observe the expression of ALK5 during the Implantation Window Stage in both human and mouse endometrial tissue, and to observe the effect of ALK5 on implantation sites by down-regulating the expression of ALK5 via in vivo transfection of plasmid. Meanwhile, we also intend to explore the relationship between ALK5 and Smad pathway by using siRNA transfection technology.

活化素受体样激酶5（Activin receptor-like kinase 5，ALK5），是TGF-β I型受体的一个主要亚型受体，在小鼠和人体子宫内膜组织研究发现，ALK5在着床期的表达明显高于非着床期；我们前期的体外研究发现，ALK5随着蜕膜化的进行逐渐升高，且给予siRNA干扰后蜕膜化不能进行。另外，ALK5在子宫内膜基质细胞中以siRNA转染后，和蜕膜化密切相关的周期素依赖的蛋白激酶抑制物p21（Smad信号通路的下游基因）也受到影响，我们推测ALK5可能通过Smad4对蜕膜化进行调控。因此，我们拟着重观察ALK5在人子宫内膜及小鼠着床期子宫内膜的表达特点，同时通过体内质粒转染改变小鼠子宫内膜ALK5的表达，观察其对小鼠着床位点的影响。另一方面我们以siRNA干扰技术对子宫内膜基质细胞进行体外处理，来探讨ALK5是否通过Smad通路调控蜕膜化，进而对胚胎着床发挥影响。

活化素受体样激酶5（Activin receptor-like kinase 5，ALK5），是TGF-β I型受体的一个主要亚型受体。我们的工作发现，ALK5及p21在人月经周期不同时段（增生早期、增生晚期、分泌早期、分泌中期、分泌晚期）子宫内膜的表达规律：发现ALK5以及P21均在分泌晚期高表达。同时小鼠假孕模型的建立，ALK5在假孕小鼠和正常妊娠小鼠D5的子宫中的表达，发现ALK5在假孕小鼠中的表达明显降低，并且siRNA干扰ALK5后，小鼠着床位点减少。结果提示ALK5在小鼠和人胚胎着床中发挥重要作用。