MicroRNA22-5p targets ten-eleven translocation and regulates estrogen receptor 2 expression in infertile women with minimal/mild endometriosis during implantation window

Abstract

Based on microRNA (miR) microarray analysis, we previously found that miR22-5p expression is decreased in the mid-luteal endometrium of women with minimal/mild endometriosis. Bioinformatics analysis predicted that miR22-5p targets ten-eleven translocation (TET2) 3 0-untranslated region. This study aimed to determine the regulation and roles of miR22-5p in the pathogenesis of minimal/mild endometriosis-associated infertility. MiR22-5p and TET2 expression in the mid-luteal endometrium from women with or without minimal/mild endometriosis was analyzed. After transfection with miR22-5p mimics or inhibitor, TET2 expression was analyzed by quantitative reverse transcription (RT-q) PCR, western blotting and immunohistochemistry. 5-Hydroxymethylcytosine was determined by immunofluorescence and dot blotting. Expression and promoter methylation of estrogen receptor 2 (ESR2) was measured by RT-qPCR and western blotting, and by bisulfite sequencing, respectively. We first established that miR22-5p expression decreased and TET2 expression increased in minimal/mild endometriosis during implantation window. TET2 was found to be a direct target of miR22-5p. MiR22-5p regulated the expression of ESR2, but did not directly affect methylation of its promoter region (-197/+359). Our results suggest that an imbalance in miR22-5p expression in the midluteal endometrium may be involved in minimal/mild endometriosis-associated infertility.

Role of endometrial microRNAs in repeated implantation failure (mini-review)

“…However, one study reported that endometrial cancer cells transfected with a miR-107 mimic had lower estrogen receptor expression . In addition, miR-22-5p transfection in endometrial stromal cells of female endometriosis in the culture medium altered the estrogen receptor expression (Xiao et al, 2020). Moreover, miR-194-3p transfection in cultured endometrial stromal cells resulted in a significant reduction in progesterone receptor protein levels (PR-A and PR-B) (Pei et al, 2018).…”

“…Transfection of miR-22 in cultured stromal cells isolated from the endometrium of female endometriosis leads to changes in estrogen receptor (ER) expression. MiR-22 suppresses the estrogen signaling pathway by targeting estrogen receptor 1 (ESR1), which is essential for the formation of the male glands (Xiao et al, 2020;Li et al, 2021;Shekibi et al, 2022).…”

Epigenetic Factors in Eutopic Endometrium in Women with Endometriosis and Infertility

“…Relatively little is known about the control of TET genes’ transcription. Recent studies have shown a relationship between decreased levels of miRNA22-5p and increased expression of the TET2 gene in the endometrium during the implantation window in patients with endometriosis [ 110 ]. All the regions of the TET promoter include CpG islands that can be potentially suppressed by DNA methylation.…”

Role of miRNAs in Normal Endometrium and in Endometrial Disorders: Comprehensive Review

“…Inversely, transfection of the same cell line with an miR-107 inhibitor resulted in an increased expression of ERα at both levels [34]. Xiao et al recently showed the impact of miR-22-5p on ERβ in endometrial stromal cells isolated from the eutopic endometrium of women with mild/severe endometriosis [35]. The transfection of these cells in an in vitro culture resulted in modifications of ERβ expression [35].…”

“…Xiao et al recently showed the impact of miR-22-5p on ERβ in endometrial stromal cells isolated from the eutopic endometrium of women with mild/severe endometriosis [35]. The transfection of these cells in an in vitro culture resulted in modifications of ERβ expression [35].…”