miR-194-3p Represses the Progesterone Receptor and Decidualization in Eutopic Endometrium From Women With Endometriosis

Abstract

Progesterone resistance in the eutopic endometrium (EuE) is suggested to be a critical factor for decreased endometrial receptivity and implantation failure in reproductive-aged women with endometriosis. Altered expression of miRNAs has been reported to play an important role in the pathophysiology of endometriosis-associated infertility. However, the underlying mechanisms of aberrant progesterone receptor (PR) and deficient decidualization regulated by miRNAs in endometriosis have not been thoroughly elucidated. The goal of this study was to explore the regulation and roles of miR-194-3p in aberrant PR expression and impaired decidualization in endometrial stromal cells (ESCs) from the EuE of women with mild or minimal endometriosis. Using a series of studies, we observed decreased PR mRNA expression and an increasing PR-A/PR-B mRNA ratio trend in the midsecretory phase of the EuE of women with minimal or mild endometriosis (n = 19) compared with controls (n = 14); the increased expression of miR-194-3p in the endometriosis group was consistent with previous microarray analysis. We also found that PR protein levels were inhibited by the transfection of ESCs with an miR-194-3p mimic and upregulated by miR-194-3p inhibition. As predicted by the bioinformatic analysis, the 3'-untranslated region luciferase assay indicated the direct regulation of PR expression by miR-194-3p. Furthermore, miR-194-3p overexpression inhibited the in vitro decidualization of ESCs via both cellular morphological changes and prolactin levels. Therefore, our study demonstrated that miR-194-3p contributes to progesterone resistance in endometriosis, which hinders fertility by repressing the levels of PR and decidualization in the EuE. Thus, miR-194-3p regulation is a future therapeutic strategy for endometriosis.

Circular RNA sequencing reveals the molecular mechanism of the effects of acupuncture and moxibustion on endometrial receptivity in patients undergoing infertility treatment

“…Estrogen and progestogen are both aromatic compounds, and the degradation of the aromatic compound pathway (PATH:01220) was significantly enriched. Analogously, protein processing in the endoplasmic reticulum pathway (PATH:04141) was also significantly enriched, and the progestogen receptor has been reported to influence the ER (20). Moreover mTOR was reported to play a part in the tumorigenesis and development of endometrial carcinoma (21), and notably, the mTOR signaling pathway (PATH:04150) was revealed to be significantly enriched.…”

Transcriptome meta-analysis reveals differences of immune profile between eutopic endometrium from stage I-II and III-IV endometriosis independently of hormonal milieu

“…Given that several pathways involving mTOR are compromised in the endometria of women with endometriosis, it is possible to hypothesize that in the normal endometrium the differentiation is more frequent and a naturally occurring process, which would justify the difference in the quantity of myocytes. Second, considering that myoblast differentiation also depends on progesterone 117 and that there is greater resistance to the action of progesterone in the endometrium of women with endometriosis 17 that is cause either by negative modulation induced by inflammation 118 or by repression promoted by miRNAs 119 , we can also hypothesize that this process is preserved in the healthy endometrium and not in the diseased one, which would also justify the difference.…”

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

“…Specifically, miR-196a upregulated MEK/ERK signaling and mediated repressed PGR expression and decidualization of endometrial stromal cells (ESCs) from eutopic endometrium with endometriosis [15]. Likewise, upregulation of miR-194-3p in eutopic endometrium inhibited PGR expression and ESC decidualization in endometriosis, which hinders fertility by repressing the levels of PGR and decidualization in the eutopic endometrium [16]. We have also shown that miR23a and miRNA23b are downregulated in endometriosis and they upregulate several unidentified genes required for Steroidogenic factor 1 (SF-1) expression in ESCs [17].…”