The endometrium is a highly complex tissue that is vulnerable to subtle gene expression changes and is the first point of contact for an implanting blastocyst. Successful blastocyst implantation can only occur when the endometrium is receptive during a short window with each menstrual cycle. microRNAs are small, non-coding RNAs that negatively regulate their gene targets. miR-29c has previously been identified to be differentially regulated across the fertile menstrual cycle, however it has not been investigated in association with infertility. We hypothesised that miR-29c dysregulation in the infertile endometrium would negatively influence endometrial adhesion and blastocyst implantation outcomes during the mid-secretory, receptive phase. miR-29c expression was elevated in early and mid-secretory phase infertile endometrium and localised to the epithelial compartments of endometrial tissue. Overexpression of miR-29c in vitro impaired endometrial epithelial adhesion, and reduced collagen type IV alpha 1 (COL4A1) mRNA expression. COL4A1 was immunolocalised to the luminal and glandular epithelial basement membranes in early and mid-secretory phase fertile and infertile endometrium for the first time. Knockdown of COL4A1 impaired endometrial epithelial adhesion suggesting a role in endometrial receptivity and implantation. Our data suggests miR-29c overexpression with infertility may impair the adhesive capacity of the endometrium, potentially contributing to implantation failure and infertility.

子宫内膜是高度复杂的组织，容易受到微妙的基因表达变化的影响，并且是植入胚泡的第一个接触点。仅在每个月经周期的短暂窗口内子宫内膜易于接受时，才能成功植入胚泡。microRNA是小的非编码RNA，会对它们的基因靶标产生负调控。以前已确定miR-29c在可育的月经周期中受到不同的调节，但是尚未与不孕症进行研究。我们假设不孕子宫内膜中的miR-29c失调会在分泌中期，接受阶段对子宫内膜黏附和囊胚着床结果产生负面影响。在分泌期和中期分泌性不孕子宫内膜中，miR-29c表达升高，并位于子宫内膜组织的上皮区室。miR-29c的过表达体外损伤子宫内膜上皮粘附，并降低IV型胶原蛋白α1（COL4A1）mRNA表达。首次将COL4A1免疫定位在分泌早期和中期分泌的可育和不育子宫内膜的腔和腺上皮基底膜上。击倒COL4A1损害子宫内膜上皮粘附，提示其在子宫内膜接受性和植入中的作用。我们的数据表明，miR-29c过度表达并伴有不育可能会损害子宫内膜的黏附能力，从而可能导致植入失败和不育。