Study The Roles Of Pericyte In The Angiogenesis Of Endometriosis

Objective:The aim of this study is to evaluate the expression of microvessel density(MVD) and pericytes number(PN) in eutopic, ectopic, normal endometrium and lesions of nude mice,and calculate the average ratio of pericyte to microvessels(PN/MVD).and make further discussion about the association between pericyte cell and angiogenesis in the endometriosis(EMs).Methods:In this study, we got20ectopic endometrium,40eutopic endometrium(20during proliferation phase,20during secretory phase) of patient with EMs and40normal endometrium (20during proliferation phase,20during secretory phase) of women without EMs.We made the nude mouse model of EMs based on the xenotransplantation of endometrial human tissue into immunodeficient mice by inoculation into the BALB/C mice peritoneal cavity. All nude mice were divided into A,B,C,D group randomly.4group mice were put to death on the7th,14th,21th,28th day after xenotransplantation, and histological structure changes of different lesions were observed grossly and micrioscopicly.Immunohistochemical staining was used to detect the expression of MVD and PN in eutopic, ectopic, normal endometrium and lesions of nude mice. As well as the average ratio of pericyte to endothelial cells in microvessels were measured.All the date were compared between these groups.Results:(1) The sussessful rate of Xenotransplantation of human endometrium into immunodeficient mice model was100%.(2) The expression of MVD in ectopic endometrium was higher than it in eutopic or control endometrium(P<0.05), while there was no statistical differences between eutopic and control endometrium, The MVD in secretory phase endometrium was higher than it in proliferative phase endometrium(P<0.05),no matter in eutopic or normal endometrium.(3) The PN in ectopic endometrium was lower than it in eutopic or control endometrium(P<0.05), still there was no significant differences between eutopic and control group, PN in secretory phase endometrium was lower than it in proliferative phase endometrium(P<0.05),no matter in eutopic or normal group.(4) The PN/MVD follow the same trend as the PN in ectopic,eutopic and normal endometrium.But the difference is that PN/MVD in eutopic endometrium was lower than it in control group(P<0.05).(5) Grossly, the lesions in A group nude mice were clear blister like, Angiogenesis was observed around lesions under microscope, MVD=35.70±3.16; The lesions in B group were shown red saccate and surface vascularity, microscopely, glands were increasing, and there was rapidly growing number of angiogenesis in and around lesions, MVD=68.60±9; The lesions in C group were darkled nodular, microscopely, the glands number reached peek, microscopely, the number of microvessel is decreased,whil the integrity and stability were increased,MVD=53.50±3.57; The lesions in D group were were yellowish-white and stale, microscopely, glands number is decreased and shriveled,the number of microvessel is continue to decline again,but remain higher compared to it in A group,MVD=48.00±4.99. The different of MVD in lesions of4group nude mice had statistical significance(P<0.05).(6) Similar changes were observed between the PN and MVD from A to D group nude mice,in order were27.30±2.50,79.40±10.68,64.70±4.64,38.30±4.50,which had statistical significance (P<0.05).(7) The PN/MVD increased from A to C group nude mice and peak at C group,then decreased in D group, but remain higher than it in A group(P<0.05)Conclusions:(1)By using xenotransplantation to make mice model of human EMs, we can achieve some dynamic observation of the histopathology processes of EMs.(2) The PN changes vary with the change in the proliferation, stabilization and degradation of EMs, coincide with MVD,imply that pericytes cell play an important role in the angiogenesis of the EMs.(3)The PN/MVD in eutopic endometrium is lower than it in normal, provide further proof of "the pivotal role of eutopic endometrium in EMs".(4)The PN/MVD in ectopic endometrium is lower than it in normal group,the PN/MVD in D group nude mouse lessions lower than it in C group,these evidence point that the high consistency of pericytes coverage rate and stability maintenance of EMs blood vessels, pericytes is expected to become a new target for EMs anti-angiogenesis therapy.(5)Furthermore, the role of pericytes of EMs angiogenesis should be paid more attention in future study.