Differential expression of microRNA in eutopic endometrium tissue during implantation window for patients with endometriosis related infertility / 中华妇产科杂志

ABSTRACT

Objective To predict the genes that affect endometrial receptivity through the differential expression of microRNA (miRNA) in eutopic endometrial tissues during implantation window in patients with endometriosis infertility. Methods Among infertile patients that received treatments at the Center for Reproductive Medicine,Peking University Third Hospital between May and December 2013, patients with endometriosis infertility were selected as endometriosis group (among the selected 17 cases, there were 6 cases with follicular phase endometrium and 11 cases with implantation window phase endometrium), and patients with tubal factor infertility were selected as control group (among the selected 19 cases, there were 7 cases with follicular phase endometrium and 12 cases with implantation window phase endometrium). (1)Implantation window phase endometrium was selected from 3 cases in each group. Using miRNA and mRNA joint gene sequencing and database for forecast results, as well as using the negative regulatory relationship between miRNA and mRNA, the intersection of target gene that negatively correlates with miRNA expression were obtained. The co-expression network of miRNA-mRNA wae constructed. Combined with the genes associated with endometrial receptivity found through bioinformatics method, the miRNA with core regulatory functionwas found. (2) Expand sample size to 14 cases for endometriosis group and 16 cases for control group.Reverse transcription (RT)-PCR technique was utilized to detect the expression of miR-142-5p, miR-146a-5p and miR-543 in endometrial tissues, and verify miRNA microarray results. Results (1) miRNA and mRNA microarray screening results showed that, among the endometrial tissues of patients with endometriosis infertility and with implantation window phase, 6 differentially expressed miRNA were indentified, among which miR-142-5p, miR-146a-5p, miR-1281, miR-940, miR-4634 showed significantly enhanced expression and miR-543 showed significantly inhibited expression. Sixty-three differentially expressed mRNA were indentified, among which 58 mRNA such as CADM1, IL-10RA, ITGAL and LPAR5 had significantly enhanced expression. Five mRNA such as HLA-DRB1,3,4,5 and SOHLH2 showed significantly inhibited expression. Thirty-six taget genes were found in consideration of negatively correlated miRNA expression with the genes, miRNA-mRNA co-expression network were constructed. The miR-543 was found at the core of the network. Targetscan and other database predicted that miR-142-5p, miR-146a-5p and miR-543 could act on various types of endometrial receptivity molecular corresponding marker genes such as HOX10, ITGAV, ITGB3, OPN, LIF, ESR, PGR, CDH1 and MMP. (2) RT-PCR test showed that the average levels of expression of miR-142-5p and miR-146a-5p in implantation window phase endometrium in endometriosis group were 8.3 ± 10.6 and 1.9 ± 0.8 respectively;the average levels of that in control group were 1.1±0.6 and 0.9±0.4, respectively. The difference was statistically significant (P=0.027, P=0.015), and was consistent with results from miRNA microarray test. The expression of miR-543 in tissues of follicular phase endometrium in endometriosis group (2.3±1.0) was significantly higher than that in control group (1.0 ± 0.4), and the difference was statistically significant (P=0.008). However, when comparing the expression of miR-543 implantation window phase endometrium in endometriosis group (1.2±0.6) with that in control group (1.5 ± 1.0), the difference was not statistical significant (P=0.890). Conclusions There are multiple differential expressions of miRNA in the implantation window phase endometrium tissues of endometriosis infertility patients, among which miR-142-5p and miR-146a-5p show significantly enhanced expression and may affect embryo implantation by acting on a variety of endometrial receptivity marker molecules. The expression of miR-543 in implantation window phase endometrium of endometriosis infertility patients is lower than that in the follicular phase, forewarned changes in the pattern of cyclic variation of miR-543, and may be the reason for affecting endometrial receptivity.