miR-297 inhibits expression of progesterone receptor and decidualization in eutopic endometria of endometriosis

Aim: Progesterone resistance is an epigenetic factor that reduces endometrial receptivity and causes implantation failure in women with endometriosis. In addition, dysregulated miRNAs contribute to the underlying pathogenic mechanisms of endometriosis. This study aimed to determine the effect of miR-297 on the progesterone receptor (PR) expression and on insufficient decidualization of endometrial stromal cells (ESCs) within the eutopic endometria of infertile women with minimal or mild endometriosis.

Methods: ESCs were isolated from infertile endometriosis and normal patients and were transfected with miR-297 mimic or miR-297 inhibitor or respective control. qRT-PCR and western blot were conducted to quantify the expression of miR-297 and PR. The effect of miR-297 on ESCs decidualization was investigated by induced decidualization in vitro.

Results: We observed an increase in miR-297 expression and a decrease in the expression of PR in the ESCs from endometriosis patients. Moreover, the expression of PR, most notably PRB, was found to be downregulated following transfection with miR-297 mimic and upregulated following treatment with miR-297 inhibitor. In addition, overexpressed miR-297 inhibited the decidualization of ESCs in vitro. We further determined that miR-297 exerts direct regulatory effects on PR expression.

Conclusions: We demonstrated that miR-297 interferes with fertility by repressing the expression of PR and preventing efficient decidualization in eutopic endometria. Further, miR-297 directly contributes to progesterone resistance in minimal or mild cases of endometriosis. Thus, regulation of miR-297 may prove to be a promising therapeutic strategy for endometriosis.