中文摘要
STRA6是维生素A摄取和代谢的关键受体。迄今为止,STRA6在胚胎着床过程中的作用还不清楚。我们的初步结果表明,与非着床位点相比,Stra6 mRNA 在小鼠妊娠第4.5天子宫着床位点显著上调,Stra6 mRNA主要表达在围绕胚胎的初级蜕膜区。Stra6子宫基质细胞基因敲除小鼠不能或者延迟着床。本课题利用多种体内、体外动物模型研究STRA6在小鼠子宫中的表达和调节规律,构建STRA6基因子宫基质细胞特异性敲除小鼠研究STRA6在早期妊娠尤其是着床和蜕膜化过程中的作用。同时利用体内和体外模型,以及先进的分子生物学技术基因芯片和免疫共沉淀(Co-IP)等方法进行其相互反应基因和蛋白,以及上、下游信号通路的研究,另外我们将阐明对小鼠着床过程中维生素A摄取和代谢的影响。本研究将为阐明STRA6维持子宫正常生理功能的分子机理提供重要依据,为胚胎着床研究和临床不孕不育治疗提供理论基础。
英文摘要
STRA6 (gene stimulated by retinoic acid 6) is a multitransmembrane domain protein, as a key membrane receptor in the process of Vitamin A uptake. To date, the function of Stra6 in the uterus during implantation are still unknown. Stra6 mRNA is significantly upregulated on implantation site in day 4.5 mouse uterus and the Stra6 mRNA mainly express on the primer decidualization in day 4.5 uterus by in situ hybridization. Moreover, the conditional uterine stromal cell STRA6 gene deletion mouse can not implantation or delayed implantation.It is suggested that Stra6 should have the important function during implantation.The aim of this project is to examine the uterine expression and regulation of Stra6 during pregnancy in mice and its regulation using the animal model in vivo and in vitro. Meanwhile, we will study the function of STRA6 during mouse different pregnancy stages for example, implantation and decidualization using the conditional uterine stromal cell STRA6 gene deletion mouse. Moreover, We will identify molecules and proteins that can directly interact with STRA6 and downstream signaling pathways affected by STRA6 deletion in mouse uterus using the Co-IP and Microarry assay and we will also learn the effect on transport of Vitamin A.Our study will not only provide valuable information for understanding the molecular mechanism of STRA6 in keeping normal function of uterus, but also provide new idea for embryo implantation research and clinical infertility treatment.
