Experimental study of antiangiogenesis therapy for endometriosis

Objective To investigate the effects of antiangiogenesis therapy on the growth and angiogenesis of established endometriosis lesions in the severe combined immunodeficiency disease(SCID)mouse model.Methods Endometrial tissue was obtained from women who underwent laparoscopy for endometriosis in the Department of Obstetrics and Gynecology,General Hospital of PLA from Jan to Apr in 2006.Eutopic endometrium was transplanted to the SCID mice,and the mice were randomized into treatment groups and control group.Two weeks after implantation of endometrium fragment,angiostatic agents were injected into the peritoneal cavity with in the treatment groups:recombinant human endostatin YH-16[(2mg/(kg·d)],thalidomide [50mg/(kg·d)],integrin аvβ3 monoclonal antibody LM609(250μg,twice/w),and vascular endothelial growth factor(VEGF)monoclonal antibody [3mg/(kg·d)].The control group was given equivalent volume sterile PBS(200μL/d).The volumes of endometriotic lesions in SCID mice were measured every three days,and all the treatment lasted 14 days.We used immunohistochemistry to determine microvessel density(MVD)so as to value the treating effect.ResultsThe SCID mouse model of endometriosis with subcutaneous inoculation can provide high survival rate of implantation,convenient observation,more visual information on the growth and response of these implants to environmental manipulation.Angiostatic angents inhibited the growth of endometriotic lesions in mice.The differences were statistically significant for the quality and volume of endometriotic lesion after treatment in YH-16 or LM609 or VEGF monoclonal antibody compared with the control group(P0.05).Microscopic examination showed the bulk of the endometrial tissue decreased and glands depauperated.The glandular epithelium had partially degenerated,and necrotic debris was presented in the endometrial stroma.MVD was decreased significantly in the groups using angiostatic angents compared with the control group(P0.05).ConclusionThe inhibitors of angiogenesis effectively interfere with the maintenance and growth of endometriosis by inhibiting angiogenesis.This suggests that the use of angiostatic agents may be promising as a therapy for endometriosis.