miR-183-5p regulates uterine receptivity and enhances embryo implantation

Abstract

Receptive endometrium is a prerequisite for successful embryo implantation, and it follows that poor endometrial receptivity is a leading cause of implantation failure. miRNAs play important roles as epigenetic regulators of endometrial receptivity and embryo implantation through post-transcriptional modifications. However, the mechanisms of action of many miRNAs are poorly understood. In this study, we investigated the role of the miR-183 family, comprising three miRNAs (miR-183-5p, miR-182-5p, and miR-96-5p) in endometrial receptivity and embryo implantation. The miR-183 family shows estrogen-dependent upregulation in endometrial Ishikawa (IK) cells. The miR-183 family also has a positive role in migration and proliferation of IK cells. Furthermore, JAr spheroid attachment experiments show that attachment rates were significantly decreased after treatment of IK cells with inhibitors for miR-183-5p and miR-182-5p and increased after treatment with miR-183-5p-mimic and miR-96-5p-mimic, respectively. The downstream analysis shows that catenin alpha 2 (CTNNA2) is a potential target gene for miR-183-5p, and this was confirmed in luciferase reporter assays. An in vivo mouse pregnancy model shows that inhibition of miR-183-5p significantly decreases embryo implantation rates and increases CTNNA2 expression. Downregulation of CTNNA2 in endometrial cells by miR-183-5p may be significant in mediating estrogenic effects on endometrial receptivity. In conclusion, miR-183-5p and the CTNNA2 gene may be potential biomarkers for endometrial receptivity and may be useful diagnostic and therapeutic targets for successful embryo implantation.

Differentially Expressed miRNAs in Mouse Uterus during Embryo Implantation

“…In this regards you may please reply of the reviewer comments mail. implantation by targeting CTNNA2 (Akbar et al 2019). MiR-183-5p was shown to be significantly differentially expressed both in their study and ours.…”

Report of Exosomes Isolated from a Human Uterine Leiomyoma Cell Line and Their Impact on Endometrial Vascular Endothelial Cells

“…Uterine leiomyomas affect reproductive outcomes, and we observed that miR-223-3p, miR-199b-5p, mir-1244, and miR-183-5p were upregulated in this study, suggesting a potential contribution to the pathology of leiomyomas. Previous studies demonstrated that miR-223-3p played a role in endometrial receptivity by regulating leukemia inhibitory factor (LIF), miR-199b-5p was present in the follicular fluid of women with PCOS and correlated with AMH levels, miR-1244 was upregulated in the follicular fluid of infertile women leading to downstream events that affect fertilization, and miR-183-5p was involved in the regulation of uterine receptivity, enhancement of embryo implantation, and invasion and migration of trophoblast cells [ 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ].…”

Circ0001470 Acts as a miR-140-3p Sponge to Facilitate the Progression of Embryonic Development through Regulating PTGFR Expression

“…During embryo implantation, the endometrium undergoes morphological and physiological changes, including cell proliferation and cell apoptosis [ 30 , 31 ]. The progression of the cell cycle commonly affects cell proliferation, and the breakdown of the cell cycle is regarded as a prevalent factor behind the repression of cell proliferation [ 32 ].…”