miR-29c overexpression and COL4A1 downregulation in infertile human endometrium reduces endometrial epithelial cell adhesive capacity in vitro implying roles in receptivity
miR-29c overexpression and COL4A1 downregulation in infertile human endometrium reduces endometrial epithelial cell adhesive capacity in vitro implying roles in receptivity
复制标题
DOI：
10.1038/s41598-019-45155-6
复制
发表时间：
2019-06-14
影响因子：
4.6
通讯作者：
Dimitriadis, Evdokia
中科院分区：
文献类型：
--
作者：
Griffiths, Meaghan;Van Sinderen, Michelle;Dimitriadis, Evdokia
子宫内膜是一种高度复杂的组织，容易受到微妙的基因表达变化的影响，并且是植入囊胚的第一个接触点。只有当子宫内膜在每个月经周期的短暂窗口内具有容受性时，囊胚才能成功植入。 microRNA 是小型非编码 RNA，可负向调节其靶基因。此前已发现 miR-29c 在整个生育周期中受到差异性调节，但尚未研究其与不孕症的关系。我们假设不孕子宫内膜中的 miR-29c 失调会对分泌中期、接受期的子宫内膜粘附和囊胚植入结果产生负面影响。 miR-29c 表达在早期和中期分泌期不孕子宫内膜中升高，并定位于子宫内膜组织的上皮区室。体外 miR-29c 的过度表达会损害子宫内膜上皮粘附，并减少 IV 型胶原 α 1 (COL4A1) mRNA 表达。 COL4A1 首次在早期和中期分泌期的可育和不育子宫内膜中免疫定位于管腔和腺上皮基底膜。 COL4A1 的敲低会损害子宫内膜上皮粘附，表明其在子宫内膜容受性和着床中发挥作用。我们的数据表明，不孕症中 miR-29c 过度表达可能会损害子宫内膜的粘附能力，可能导致植入失败和不孕症。
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.