| AIM: Though extensively investigated, the etiology of endometriosis has remained enigmatic. The retrograde menstruation and implantation of endometrial fragments is a primary mode of developing endometriosis in the peritoneal cavity, but this phenomenon is nearly universal. Some reports have stated that matrix metalloproteinase ( MMP ) and its specific inhibitors ?tissue inhibitor of metalloproteinase ( TIMP ), especially the action and interaction of type IV collagenase and TIMP-l,TIMP-2 may play an important role in it. Up to now, it hasn't been reported whether or not membrane-type I matrix metalloproteinase(MTl-MMP) is involved in endometriosis, though MT1-MMP is an activator of proMMP-2. Our current understanding of the epidemiology of endometriosis dictates that a woman's exposure to endogenous or exogenous steroids is closely linked to her overall risk of developing endometriosis. While acting as an antagonist of progesterone, Mifepristone*has been used to treat endometriosis. In the present study, we detected the expressionof MTl-MMP, MMP-2, MMP-9 and TIMP-1JTMP-2 in the level of tissue and cells and investigated the interaction between them. We also detected the action of steroids and Mifepristone on endometrial cells and on the expression of MMPs,TIMPs, in order to find out the etiology of endometriosis and ques the best therapy project.Method: 1. By in situ hybridization (ISH) , the expressions of MTl-MMP, MMP-2 and MMP-9 mRNA were detected in 29 normal endometriums and 30 endometriosis ectopic endometriums. 2.By immunohistochemical staining, the expressions of protein of MMP-2,MMP-9,TIMP-1 and TIMP-2 were detected in 84 normal endometriums and in 79 ectopic and 48 eutopic endometriums in endometriosis. 3. Ectopic endometrial cells from 6 endometriosis women and normal endometrial cells from 2 hysteromyoma women were cultured in vitro, and the normal endometrial cells were treated with Estradiol, Progesterone and Mifepristone. Cell grouth curves of both normal and ectopic endometrial cells were drawn through MTT method and their morphologic changes were observed under invert microscope and electron microscopy. The expressions of MMP-2, MMP-9, TIMP-1 and TIMP-2 were detected with immunohistochemical staining and were measured with a computerized image analysis system.The changes of cell cycle and concentration of intracellular calcium ([Ca2+]i) in treated normal cells and ectopic cells were detected with FCM and LSCM respectively. The data was analyzed with SPSS 10.0 statistical software.RESULTS: 1. (1) The expression of MTl-MMPmRNA was not found detected in normal endometrium while in ectopic endometrium in endometriosis only 26.67% were detected (P<0.01); (2) MMP-2mPxNA was also mainly detected in normal proliferative phase endometriums, with positive rate 20.69%, and that in ectopic endometrium in endometriosis 56.67%(P<0.01); (3) MMP-9mRNA was only detected in normal proliferative phase endometriums, with positive rate as low as 6.90%, whilein ectopic endometrium in endometriosis the positive rate is up to 43.30%(.P<0.01); (4) There is a notable positive correlation between the expression of MMP-2 and MT1-MMP, however, there is no correlation between the expression of MMP-9 and MT1-MMP in endometriosis. 2. (1) We found low positive rates of MMP-2 and MMP-9(57.14% , 40.48% respectively) expression in normal endometriums, and expression level is positive ++ maily in proliferative phase and positive + maily in secretory phase, while there was high positive rate of MMP-2 and MMP-9 in ectopic endometriums(78.48%, 72.15% respectively), besides their expression level was positive ++ maily (P<0.01); The expressions of MMPs in eutopic endometriums in endometriosis were between normal and ectopoic endometriums (P<0.05). (2) The proteins of TIMP-1 and TIMP-2 expressed high in normal endometriums with positive ++ and positive + in secretory and proliferative phase respectively, whereas there was low positive rate of TIMP-1 and TIMP-2 in ectopic endometriums with positive ++ ma... |
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