P-136: Association of Matrix MetalloProteinase- 2,-9 Overexpression and Imbalance PR-A/PR-B Ratio in Endometriosis

Background: Matrix MetalloProteinases (MMPs) degrade extracellular matrix components to provide normal remodeling and contribute to pathological tissue destruction and cell migration in endometriosis. It is accepted that MMPs are resistant to suppression by progesterone in endometriotic tissues. The physiological effects of progesterone are mediated by its two progesterone receptor (PR) isoforms, namely PR-A and PR-B. The capacity of progesterone affect to gene expression is dependent on the PR-A/PR-B ratio. The imbalance ratio in endometriotic tissue may be an important mechanism to be resulted in progesterone resistance and modify progesterone action via differential regulation of specific progesterone response genes and improve endometriosis disease. Materials and Methods: RNA was extracted from twenty ectopic (endometriotic) and eutopic (endometrial) tissue sam ples of women undergoing laparoscopy for endometriosis and 20 healthy fertile women at Royan Institute, Tehran, Iran. Analysis of PR-A, PR-B, MMP-2 and MMP-9 mRNA expression was performed using Real-time PCR in ectopic and eutopic tissues. Results: Quantitative RT–PCR analyses of PR-A and PR-B mRNA revealed that there was significance different in mRNA expression level of PR-A/PR-B ratio between ectopic, eutopic and control tissues. We were able to demonstrate low expression levels of PR-B isoforms in ectopic tissues. Although, PR-A expression was higher in the same ectopic samples compared to control groups. This method permitted us to demonstrate overexpression of MMP-2 and significant high level of MMP-9 expression in ectopic tissues compared to control groups, as well. Conclusion: Our data suggest that low expression levels of PR-B and overexpression of PR-A can alter PR-A/PR-B ratio in endometriotic ectopic tissues. Imbalance ratio of PRs in endometriotic tissue may be able to consequence MMP-2 and MMP-9 overexpression which can be important in pathogenesis and treatment of disease.