Matrix metalloproteinase 2 (MMP-2), membranous type 1 matrix metalloproteinase (MT1-MMP) and tissue inhibitor of metalloproteinase 2 (TIMP-2) mRNA expression in ectopic and eutopic endometrium

Objective: In endometriosis patients, refluxed menstrual debris is more prone to implant and invade peritoneum or ovary possibly through the action of extracellular proteolysis. This proteolytic action may involve the collagenase system. Matrix metalloproteinases (MMPs) play a critical role in the breakdown of extracellular matrix components and basement membrane in the processes of ovulation, implantation, tumor invasion and metastasis. MMP-2 activity is inhibited by TIMP-2 and the latent MMP-2 precursor form is cleaved by MT1-MMP into mature MMP-2. To test the hypothesis that higher expression of MMP-2 and MT1-MMP and lower expression of TIMP-2 in ectopic and eutopic endometrium from women with endometriosis might favor increased proteolytic enzyme activity with subsequent endometriotic invasion, we investigated their mRNA expression. Design: MMP-2, MT1-MMP and TIMP-2 mRNA expression in ectopic and eutopic endometrium from women with endometriosis and eutopic endometrium from control patients without endometriosis were determined by QC-PCR throughout the menstrual cycle. Materials/Methods: Endometrial tissue was obtained from 23 patients with severe endometriosis (ectopic endometrium was also obtained in 21 of these women) and 30 patients without endometriosis undergoing hysterectomy or endometrial biopsy. Stage of endometrial cycle and a diagnosis of endometriosis were confirmed histologically. Total RNA was extracted and reverse transcribed into c-DNA. QC-PCR was performed to evaluate MMP-2, MT1-MMP and TIMP-2 mRNA expression. Results were analysed by Post Hoc test. Results: Uterine endometrium from women with endometriosis expressed significantly (p < 0.05) higher levels of MMP-2 and MT1-MMP and significantly (p < 0.05) lower levels of TIMP 2 than endometrium from normal women. Also, ectopic endometrium expressed lower levels of MMP-2, MT1-MMP and TIMP-2 than eutopic endometrium from normal and endometriosis patients. Conclusions: These results suggest that eutopic endometrium from endometriosis patients may be more invasive and prone to peritoneal implantation because of greater MMP2 and MT1-MMP and lower TIMP2 mRNA expression than endometrium from women without endometriosis. Thus, increased proteolytic activity may be one of the reasons for the invasive properties of the endometrium resulting in the development of endometriosis. Supported By: No support.