Mir-135可通过调控HOXA10基因促进子宫内膜容受性的建立？

The implantation process is complex, requiring reciprocal interactions between implantation-competent blastocysts and the receptive uterus. Because microRNAs (miRNAs) have major roles in regulating gene expression, we speculated that they participate in directing the highly regulated spatiotemporally expressed genetic network during implantation. In our previously study, Microarray profiling identified hat miR-135b was are spatiotemporally expressed in the endometrium during the window of implantation. Using Taget Scan software, showed miR-135 were predicted to regulate HOXA10. HOXA10 regulates endometrial receptivity. We hypothesized a role for microRNA in the regulation of HOXA10. The aim of the study is to measurement of the miR135 expression; to analysis the regulation of the HOXA10 in vitro; To examine the influence of ovarian steroids , their respective antagonists and embryo on the expression of miR135 in coculture system in vitro. Though the study, we hypothesized that miR135 tagets the HOXA10 gene and regulates its function by expression of HOXA10 mRNA and protein. Thus, elucidating thephysiological roles of uterine miRNAs will help us better understand the genetic control of implantation, the gateway to a successful pregnancy. Accordingly, miRNAs are potential therapeutic targets for treating the infertility.

子宫内膜容受性的建立是胚胎成功着床的第一步，关键基因HOXA10作为子宫内膜容受性的标志物，发挥了重要作用，但仍需进一步研究。课题组预实验显示，与着床前期相比，子宫内膜着床窗口期mir-135表达下调，应用Taget Scan软件进行靶基因分析和信息对比，高度提示HOXA10是miR-135的靶基因。本课题在预实验的基础上，检测miR-135在人类子宫内膜着床窗口期的表达和对靶基因HOXA10的调控效应；建立子宫内膜-滋养细胞体外共培养体系，研究过表达和抑制表达miR-135对胚胎粘附及对HOXA10的影响；进一步探讨卵巢甾体激素及其拮抗剂、胚胎对miR-135的调节作用，旨在证实miR-135可以通过调控HOXA10促进子宫内膜容受性的建立。本研究将深化胚胎着床和子宫内膜容受性建立的基础研究；并可能为不孕症的临床诊治提供新的靶点。

关键基因的激活在子宫内膜容受性的建立过程中发挥重要作用。课题组预实验在人子宫内膜着床期miR-135存在差异表达。本课题以miR-135为切入点，研究其是否通过调控子宫内膜容受性关键基因HOXA10促进了子宫内膜容受性的建立。课题结果显示miR-135过表达可抑制靶基因HOXA10的表达，而mi-R135的沉默表达可上调子宫内膜HOXA10的表达，同时进一步研究还发现，mi-R135的沉默表达在上调子宫内膜HOXA10的同时，HOXA10 的下游基因的表达增强，这些都提示了子宫内膜着床期子宫的容受性的建立。体外共培养实验结果提示过表达或抑制表达miR-135对可调节胚胎的黏附。该实验结果明确miR-135在子宫内膜容受性建立中发挥重要作用，为揭示胚胎着床机理并针对性地调节相关的miRNAs表达，从而促进子宫内膜容受性的建立来治疗不孕或发展新的抗生育技术奠定基础。