Study On The Function Of Hmga2 In The Endometrial Receptivity

Endometrial receptivity refers to the ability of the endometrium to be receptive to embryonic implantation.It is challenging to identify candidate genes of endometrial receptivity to unveil the underlying mechanism of embryo implantation,to improve pregnancy rate and to increase litter size.The prerequisites to form receptive state of endometrium are proliferation and differentiation of endometrial stromal cells.Hmga2 plays a critical role in the regulation of gene expression,cell proliferation and differentiation.However,its function and molecular mechanisms in endometrial receptivity remain elusive.Patients with polycystic ovary syndrome(PCOS)are prone to have low pregnancy rate and high fetal mortality due to the reduction in endometrial receptivity.In this study,the expression,function and molecular mechanisms of Hmga2 during endometrial receptivity and embryo implantation have been studied in vitro and in vivo.Firstly,we have studied the regulation of expression with HESCs in vitro.The results showed that after induced decidualization,the expression of Hmgga2 in HESCs and cell proliferation were increased significantly.Besides,the mRNA expression of molecular markers of decidualization increased significantly,including Igfbpl and Prl,and their expression decreased significantly after down-regulating Hmga2.Secondly,higher expression of Hmga2 was observed in implantation site during pregnancy.In mice uterus,the delayed implantation and activation experiments confirmed that the expression of Hmga2 in embryo activation group was significantly higher compared with delayed implantation group.In addition,after induced decidualization,we found that Hmga2 expression of uterus in induced decidualization group was significantly higher than control group,Moreover,Hmga2 was involved in the proliferation and differentiation of mouse uterine stromal cells.In ovariectomized mice progesterone and estrogen injected subcutaneously increased the Hmga2 expression in uterus,we made the PCOS mouse model with dihydrotestosterone(DHT),confirmed by hyperandrogenemia,polycystic ovarian and insulin resistance.In the PCOS model,the expression of Hmga2 of parametrium was significantly lower than control group.Finally,The pig endometrial samples were collected at different implantation stages.Results showed that Hmga2 expressed mainly in the functional area of the endometriumand like mice the expression of the embryo attachment sites was much higher.The expression of Hmga2 peaked on the 18th day after pig breeding,and its expression decreased gradually on the 24th day after pregnancy.Taken together,the present study showed that Hmga2 in endometrial stromal cells involved in the process of decidualization and may affect endometrial receptivity.Moreover,In mice the expression of Hmga2 changed regularly in early pregnancy,and was influenced by estrogen,progesterone and activated blastocyst.High androgen can cause reproductive endocrine disorders,down-regulate the expression of Hmga2,and reduce endometrial receptivity,which leads to low pregnancy rate and high abortion rate in early pregnancy.In pigs the expression of Hmga2 increased initially and then decreased in the embryo attachment stage.We propose that Hmga2 is a key gene to regulate endometrial receptivity and embryo implantation.This study potentially opens up new vistas of the Hmga2 in endometrial receptivity,embryo implantation and to help improve pregnancy rate and raising pig benefits.