子宫内膜容受性欠缺是造成胚胎着床失败的主要原因，我们前期的研究发现α-actinin，一种肌动蛋白交联蛋白，在子宫内膜存在周期性变化，种植窗期时其表达显著下降，这种变化很可能与子宫内膜容受态的建立相关。然而还未明确α-actinin在子宫内膜的精细时空表达规律，以及其在子宫内膜容受态建立中的确切作用和调控机制。本课题拟首先通过免疫组化的方法明确α-actinin及其磷酸化活化状态在整个月经周期的表达模式;随后分析调控α-actinin基因表达的转录因子;再通过细胞株体外实验，明确α-actinin的过表达或siRNA干扰是否直接改变了子宫上皮细胞肌动蛋白纤维的聚合进而影响了细胞的粘附功能，同时，直接观察其过表达或siRNA干扰对滋养细胞与内膜上皮细胞结合能力的影响；最后，通过动物在体实验，观察子宫α-actinin条件敲除小鼠生育力的变化，验证α-actinin在子宫内膜容受态建立中的作用

It is thought that most of implantation failures result from abnormal uterine receptivity. Our previous study found that α-actinin，an actin filament crosslinking protein，exhibited cyclic changes in endometrium and downregulated during “implantation window”，such changes may have relationship with endometrium receptivity. However, the exact expression pattern and molecular mechanism remains poorly understood. Based on these important findings, our project will keep to carry out the following work: Analysis expression pattern of α-actinin and phosphor-α-actinin during a intact cycle ;Analysis of upstream regulator of α-actinin genes using co-transfection and luciferase reporter assays；Analysis the function of α-actinin in endometrial cells using gene over-expression and interference; Prove the function of α-actinin in vivo by conditional knockout. Demonstration of these issues will clarify the role of α-actinin in adjustment of endometrium receptivity and provide new theoretical basis and intervention targets to improve endometrium receptivity in clinic.