The Effect Of Estrogen And Progestion On The Expression Of Matrix Metalloproteinase2, Tissue Inhibitor Of Metalloproteinase2 And Vascular Endothelial Growth Factor In Nude Mouse Endometriosis Model

Objective: To observe the effect of estrogen and progestin on the morphology andbiological behavior of human endometrium transplanted into nude mice, and the effects ofmatrix metalloproteinase2(MMP-2), tissue inhibitor of Metalloproteinase2(TIMP-2) andvascular endothelial growth factor(VEGF) in endometriosis.Method: 60 nu/nu mice were injected with the late secretory endometrial chippingand then were randomly devided into 4 groups: one group were injected with estrogen,one group with progestin, one group witn estrogen and progestin, and the control groupwith sodium chloride. The mice were killed on d18 and the grafts were obtained. Theexpressions of MMP-2,TIMP-2 and VEGF in the grafts and normal endometrium weredetected by immunohistochemistry method.Result : Typical endometrial glands and stroma were observed in all groups, andamong which the implantation rates were not significant. The administration of progestinsupplementation in vivo was associated with multiple peritoneal implantation sites andwith significantly larger implants. Proliferation of endometrial gland cells occurred in thetransplanted endometrium of estrogen-treated mice, and progestin could causesecretory-phase changes; the late secretory endometrial chipping showed proliferativeafter transplanted into nude mice without administration of sexual homone. The endometriotic lesions show an increased expression of MMP-2 and VEGF and andecreased expression of TIMP-2. Estrogen or progestin could increase the ratio ofMMP-2/TIMP-2 and the expression of VEGF and progestin couldn't antagonize the effectof estrogen on the expression of MMP-2 and VEGF.Conclusion: The nude mouse is an appropriate model to study the response ofearly-phage ectopic endometrium to sex steroid. The response appears to be atypical whencompared to normal endometrium. The ectopic endometrium have enhanced ability ofinvasion and angiogenesis. Progestrin can't inhibit the expression of MMP-2 and theeffect of estrogen on ectopic endometrium, which is called progestrin resistance.