Study On Matrix Metalloproteinase-9 And Its Special Inhibitor In Endometriotic Tissues Of Women With Endometriosis

Background Endometriosis is one of the most common benign gynecologic disorders. The pathogenesis is not completely understood. The most widely accepted theory is that of retrograde menstruation introduced by Sampson. According to Sampson's theory, fragments of endometrium are refluxed through the fallopian tubes into the peritoneal cavity, then attach and grow on ovarian and peritoneal surfaces.And establishment of ectopic sites requires breakdown of extracellular matrix. Matrix metalloproteinases(MMPs) play an important role in degradhg and remodeling the extracellular matrix. MMPs are a family of zinedependent enzymes that degrade components of the extracellular matrix. The activity of MMPs is tightly regulated by a family of natrual inhibitors known as tissue inhibitors of metallopiteinase (TIMPs). Recently, some studies documented that MMPs and TIMPs, which have been localized to endometriotic tissue, may be involved in the development and progression of endometriosis. The implantation and invasive growth of endometriotic tissues & similar to the metastasis of tumor cells. So the gelatinases (i.e. MMP-2 and MMP-9), which are closely associated with the metastasis of malignant tumors, have been most studied. Objective To investigate the expression of matrix metalloproteinase9 (MMP-9) and tissue inhibitor of metalloproteinase1 (TIMP-1) in endometriotic tissues and uterine endometria from women with and without endometriosis throughout the menstrual cycle. And to determine whether MMP-9 and TIMP-1 contribute to the pathogenesis of endometriosis. Methods and Results1. Tissue specimens were obtained from patients with and without endometriosis. The MMP-9 activity of ectopic and eutopic endometrium was detected by zymography and quantitiated by Gel Documentation Analysis System. The study demonstrated that the activity of MMP-9 latent form is present in all endometria and endometriotic tissues. Protein expression of MMP-9 of endometriotic tissues is significantly higher than that of eutopicendometria of women with and without endometrfosis (P<0.01). However, expression of MMP-9 in uterine endometria with and without endometriosis is not significantly different (P>0.05). And there was a trend toward increasing levels of MMP-9 between AFS stage I - II , III and IV endometriosis.2. In this section we detected mRNA expression of MMP-9 and its inhibitor TIMP-1 with reverse transcription polymerase chain reaction technique. The results showed that the levels of TIMP-1 mRNA in endometriotic tissues is significantly lower than that of uterine endometria from women with and without endometriosis(P<0.01). Also the levels of MMP-9 mRNA and ratio of MMP-9 to TIMP-1 in ectopic endometria are remarkably higher than that of ectopic endometria(P<0.01). These data are compatible with the altered expression of MMP-9 protein.Conclusion These results suggested that ectopic endometria from endometriosis patients may be more invasive and prone to implantation because of greater MMP-9 and less TIMP-1 expression than uterine endometria. Thus, increased proteolytic activity may be one of the reasons for the invasive properties of the endometriotic implants, resulting in the development and progression of endometriosis.