The Study Of The Effects Of MicroRNA-183 Family On The Uterine Receptivity And Embryo Implantation

Background:Receptive endometrium is a prerequisite for successful embryo implantation,and it follows that poor endometrial receptivity is a dominating cause of implantation failures.MicroRNAs(miRNAs/miRs)play important roles as epigenetic regulators in endometrial receptivity and embryo implantation through post-transcriptional modifications.However,the mechanisms underlying the actions of many miRNAs are not well-understood.In this study,we investigated the role of the miR-183 family,comprising three miRs(miR-183-5p,miR-182-5p,and, miR-96-5p),in endometrial receptivity,and,embryo implantation Methods:We used human endometrial cell line(Ishikawa cell,IK)for in-vitro assays to analyze the effects of miR-183 family on functional properties of endometrial cells In-vitro JAr spheroid attachment model was used to observe effects on embryo implantation.Target gene prediction of miR-183 family was done using target gene predicting softwares and luciferase reporter assay was used for target validation In-vivo mouse pregnancy model was used to affirm the role of miR-183-5p on embryo implantation.We also collected endometrial samples from women who underwent in vitro implantation and embryo transfer.Results:We found that the miR-183 family was estrogen-dependently up-regulated in endometrial IK cells.The miR-183 family had a positive role in proliferation and migration of IK cells.Furthermore,JAr spheroid attachment experiments showed 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 showed 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 showed that inhibition of miR-183-5p significantly decreased embryo implantation rates and increased CTNNA2 expression.In the clinic,we found that the expression levels of endometrial miR-183-5p in the failed pregnancy group were significantly lower than that in the successful pregnancy group.Meanwhile,the expression levels of CTNNA2 in the failed pregnancy group were significantly higher than that in the successful pregnancy group.Down-regulation of CTNNA2 in endometrial cells by miR-183-5p may be significant in mediating estrogenic effects on endometrial receptivity.Conclusion:miR-183-5p and the CTNNA2 gene may be potential biomarkers for the endometrial receptivity,and,may be useful diagnostic and therapeutic targets for successful embryo implantation.