Study The Mechanism For Human Chorionic Gonadotropin Potentially Affects Endometrial Receptivity By Promoting HOXA10

Object:The aim of this study was to assess mechanism for human chorionic gonadotropin potentially affects endometrial receptivity by promoting homeobox A10(HOXA10).Methods:The expressions of HOXA10 and DNA methyltransferases 1(Dnmt1)in human recurrent implantation failure endometrium were further analyzed by Western blot.The expression and location of HOXA10 in endometrium were detected by immunohistochemical staining.The expressions of HOXA10 and DNA methyltransferases 1(Dnmt1)in human endometrial stromal cells(hESCs)after treatment with human chorionic gonadotropin were further analyzed by Western blot or qRT-PCR.Moreover,the in vitro embryo implantation model was used to prove the hCG-mediated function of enhanced HOXA10 on decidualization in hESCs.In addition,the expressions of HOXA10 and Dnmtl in recurrent implantation failure endometrium were analyzed by Western blot after intrauterine injection treatment with human chorionic gonadotropin before embryo transfer.Results:Dnmtl expression was increased in endometrial tissues from the RIF patients(n=11)compared with those from the fertile controls(n=11)and the opposite results were observed for HOXA10 in these tissues(P=0.0432,P=0.0453).HOXA10 localized in human epithelium and stromal cells.Addition of 0.2IU/mL human chorionic gonadotropin to hESCs induced the increase of HOXA10 and decrease of DNA methyltransferases 1(Dnmtl)at 48h(both P<0.01 versus control).HOXA10 mRNA levels were significantly increased 2.70 times by human chorionic gonadotropin 0.21U/mL treatment for 48h(P<0.01).Dnmtl mRNA levels were decreased 0.69 times after treating with human chorionic gonadotropin 0.2IU/mL for 48h.Human endometrial stromal cells were treated with human chorionic gonadotropin 0.2IU/mL up to 48h showed a good decidual response,mainly haracterized by increased BLS expansion.The expression of HOXA10 was increased in endometrial tissues from the RIF patients(n=5)after intrauterine injection treatment with human chorionic gonadotropin compared with theselves before(P=0.0005)and the opposite results were observed for Dnmtl in these tissues(P=0.0053).Conclusion:Our results suggest that the expression of HOXA10 in human recurrent implantation failure endometrium were lower and Dnmtl had a higher expression.Human chorionic gonadotropin activates the expression of HOXA10 and down-regulate Dnmtl expression in human endometrial stromal cells(hESCs).The expression of HOXA10 was increased in endometrial tissues from the RIF patients after treatment with intrauterine injection human chorionic gonadotropin compared with theselves before and the opposite results were observed for Dnmtl in these tissues.Human chorionic gonadotropin may activate the expression of HOXA10 by down-regulating Dnmtl.These finding may subsequently provide the theoretical basis for improving the success rate of embryo implantation and the novel potential therapeutic regimens for recurrent implantation failure patients with poor decidualization.