调经促孕方对胚胎着床障碍性不孕症小鼠子宫内膜容受性及AREG/EGFR/HIF-1α信号通路的影响OACSTPCD

Objective To observe the effects of Tiaojing Cuyun Prescription on endometrial receptivity and AREG/EGFR/HIF-1α signaling pathway of embryo implantation dysfunction(EID)infertility mice;To explore its mechanism on improving endometrial receptivity.Methods On the first day of pregnancy,80 Kunming mice were randomly divided into control group,model group,progesterone group and Tiaojing Cuyun Prescription group,with 20 mice in each group.Progesterone group and Tiaojing Cuyun Prescription group were given corresponding drugs by gavage.On the fourth day of pregnancy,mifepristone solution was subcutaneously injected(2.3 mg/kg)to establish the EID infertility model except the normal group,while the normal group was subcutaneously injected with equal volume of propylene glycol.On the fifth day of pregnancy,10 mice were randomly selected from each group,and the endometrium morphology were observed by HE and Masson staining,the pinopodes were observed by scanning electron microscope,the content of AREG in endometrial tissue was detected by ELISA,and the expressions of EGFR,p-EGFR and HIF-1α were detected by Western blot and immunofluorescence,the rest of the mice were gavaged until the eighth day of pregnancy,and the average number of embryo implantation points was recorded.Results Compared with the normal group,the average number of embryo implantation points of model group significantly decreased(P<0.01),and the glandular development in the endometrium was poor,collagen fibers increased,and blood vessels and pinopodes decreased,the AREG content in endometrial tissue was significantly decreased(P<0.01),and the expressions of p-EGFR and HIF-1α protein were significantly decreased(P<0.05).Compared with the model group,the average number of embryo implantation points in Tiaojing Cuyun Prescription group significantly increased(P<0.05),the proliferation of collagen fibers in the endometrium was reduced,and the number of glands,blood vessels and pinopodes in stroma significantly increased,the development of pinopodes were full and uniform,the AREG content in endometrial tissue significantly increased(P<0.01),and the expressions of p-EGFR and HIF-1α protein significantly increased(P<0.05,P<0.01).The immunofluorescence results were consistent with Western blot.Conclusion Tiaojing Cuyun Prescription can promote the development of endometrial glands and blood vessels,enrich the number of pinopodes,improve the endometrial receptivity of EID infertility mice,facilitates embryo adhesion and implantation,and thus increase the pregnancy rate.Its mechanism may be related to activating AREG/EGFR/HIF-1α signaling pathway,improving endometrial perfusion,and restoring the relatively hypoxic environment of the endometrium.