Expression And Clinical Significance Of Matrix Metalloproteinase-3 MRNA And Tissue Inhibitor Of Metalloproteinases-3 MRNA In Endometriosis

Objective: MMPs systems are implicated in the establishment of endometriosis. The mechanisms by which these systems are involved in pathogenesis of this disease are not well defined and controversial results have been published.The aim of this study was to analyse mRNA levels of MMP-3 and TIMP-3 in endometriotic tisse and endometrium from women with and without endometriosis and to explore the correlation between the two factors expressioned in endometriosis.Methods: RT-PCR assays were developed to detected the gene expression of mRNA levels of MMP-3 and TIMP-3 in 38 women with endometriosis (16 cases with active peritoneal implants , 22 cases with ovarian endometrioma) , 20 cases endometrium from women with endometriosis ,and 25cases normal endometrium as controls.Results: (1) The endometrium of women with endometriosis showed higher mRNA levels of MMP-3 than endometrium from controls(P<0.05);In thses patiens, Peritoneal endometriotic tisse had higher mRNA levels of MMP-3 than that of ovarian endometriotic tisse (P<0.05).(2)The expression of MMP-3 mRNA in those of eutopic endometrium with endometriosis is higher than endometrium without endometriosis (P<0.05).(3) Compared with Peritoneal endometriotic tisse and controls, ovarian endometriotic tisse had higher mRNA levels of TIMP-3 (P<0.05).?There appeared an imbalance of the levels between MMP-3 and TIMP-3 expressioned in the group of ectopic endometrium and the expressions of MMP-3 and TIMP-3 were detected both in proliferative phase and secretory phase which was not related to menstrual cycle. (P>0.05).Conclusions: (1)The increase in mRNA levels of MMP-3 observed in endometrium of women with endometriosis may facilitate the the invasion of endometrial tissiue to the peritoneum and ovarian surface. This process would lead to the formation of early endometriotic lesion. These results support the hypothesis that MMP-3 is an important mediator of cellular invasiveness during early endometriotic lesion.(2) Once the ovarian endometriotic cyst is developed, TIMP-3 would increase which could explain the frequent clinical finding of an endometriotic cyst without invasion of the adjacent ovarian tissue, and suggest that TIMP-3 serves as a regulator within the uterus to restrict invasion to the site of implantation ^specially in advanced stage of endometriosis.(D The changed expression between MMP-3mRNA and TIMP-3mRNA in the ectopic endometriotic tissue of different stage result in imbalance expression between them, which are suggested to be of importance for the more implantation and invasive capacity for ectopic endometriotic tissue to form early endometriotic lesion, and gradually ectopic endometriotic tissue lose the activity of invasiveness in advanced stage of endometriosis.