The Expression And Significance Of Matrix Metalloproteinase-1 And Tissue Inhibitor Of Metalloproteinase-1 In Endometriosis

Objective: To investigate the expression of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the eutopic and ectopic endometrium from women with endometriosis, thereby to determine the role of matrix metalloproteinases and their inhibitors in the pathogenesis of endometriosis.Methods: Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical streptavidin-peroxidase (S~P) were employed to detect the gene and protein of MMP-1 and TIMP-1 in 45 ectopic endometrium and 22 eutopic endometrium from women with endometriosis and 20 normal control endometrium.Results: (1) The relative amounts of MMP-1 gene in ectopic endometrium was(l. 33±0. 41), and significantly higher than that in eutopic endometrium from women with (1.06 ±0.35) and without (0. 91 ± 0. 32) endometriosis, P<0. 01. The relative amounts of TIMP-1 gene in ectopic and eutopic endometrium from endometriosis patients were (1.12 ± 0.51) and (1.39 ± 0.46), respectively, and both were lower than that of normal endometrium(l. 74± 0. 43), P<0. 05. (2) The staining of MMP-1 protein in the stromal and glandular cell's of ectopic endometrium were -moderately and severely positive, and were higher than that of eutopic endometrium from women with and without endometriosis (P<0.05). The staining of TIMP-1 protein in the stromal and glandular cells of ectopic and eutopic endometrium in endometriosis were both mildly positive, and were significantly lower than that of normal endometrium (P<0. 01). (3) And the ratio of MMP-1/TIMP-1 gene in ectopic and eutopic endometrium from endometriosis patients were (1.46 ±0.57) and (1.39± 0. 46), respectively, and significantly higher than that of normal endometrium (0. 87±0. 47), P<0. 01 or P<0. 05. (4) The expression of MMP-1 gene and protein in stage IV was significantly higher than stage I~II , P<0. 05, while the expression of TIMP-1 gene and protein were irrespective of the clinical stage>0. 05. (5) The expression of gene and protein, of MMP-1 and TIMP-1, in the eutopic endometrium from women with and without endometriosis, were all significantly relevant to the phase of the menstrual cycle (P<0. 05), while those in ectopic endometrium was not (P>0.05). Conclusion: (1) The expression of greater MMP-1 and lesser TIMP-1 in theectopic endometrium from endometriosis patients result in the imbalance between MMP-1 and TIMP-1 , which may make ectopic endometrium degrade extracellular matrix accellarately, invade and implant peritoneum, and may play an important role in the pathogenesis of endometriosis. (2) The lesser expression of TIMP-1 in eutopic endometrium from women with endometriosis make the ratio of MMP-1/TIMP-1 increase, and MMP-1 degrade extracellular matix accelerately, which may lead to eutopic endometrium from women with endometriosis more invasive and prone to peritoneal implantation, and may play some accelerational role in the pathogenesis of endometriosis. (l)The expression of MMP-1 in ectopic endometrium from endometriosis patients is higher than that in normal endometrium, and as endometriosis clinical stage increase, the expression of MMP-1 strengthen, which play an vital role in the pathogenesis of endometriosis and may lead to endometriosis progression. (4) The expression of MMP-1 and TIMP-1 in ectopic endometrium of endometriosis lost menstrual cycle expression in normal endometrium, which may be one of failure reason of hormone therapy to endometriosis.Postgraduate Zhou Hui (Obstetrics and Gynecol) Directed by Prof. Guo Xinhua...