#111 : MMP-9 to TIMP-1 Expression Ratio on Endometrioma Favors Tissue Invasion: A Study on Chicken Chorioallantoic Membrane (CAM)

Abstract

Background and Aims: Endometrioma occurs through the implantation of endometrial tissue in the ovary. The establishment of endometriotic lesions requires endometrial cells to invade the ovary by remodelling the extracellular matrix (ECM). It is plausible that these cells express protease. MMP-9 is a significant protease controlled by its natural inhibitor, TIMP-1. The balance between MMP-9 and TMIP-1 plays a critical role in the invasion of endometrioma that has never been investigated before. This study aimed to examine the correlation between MMP-9/TIMP-1 expression ratio and MMP-9 activity with the invasion of endometrioma tissue. Method: This study was conducted on 35 samples of endometrioma tissue obtained from 27 women with endometriosis at Dr Sardjito General Hospital, Yogjakarta. The tissue was then implanted into CAM to examine its invasion capability. Invasion scores were assessed using hematoxylin-eosin staining. MMP-9/TIMP-1 expressions ratio was analysed using western blot, while MMP-9 activity in degrading ECM components was determined using gelatin zymography. The Spearman correlation assesses the correlation between variables with significance set as p[Formula: see text]0.05. Results: The results showed a positive linear correlation between the MMP-9/TIMP-1 expression ratio and invasion scores of endometrioma tissue (r=0.486; p=0.003). In addition, the Kruskal-Wallis test showed there was a significant difference between the MMP-9/TIMP-1 expression ratio in each invasion score of endometrioma (p=0.032), and further analysis by Mann-Whitney post hoc tests revealed that significant differences were between invasion score 1 and 3 (p=0.037), also between invasion score 1 and 4 (p=0.010). MMP-9 activity had a strong positive linear correlation with invasion scores of endometrioma tissue (r=0.646; p=0.000). Conclusion: MMP-9 activity in degrading extracellular matrix promotes the invasion of endometrioma. The imbalance between MMP-9 and TIMP-1 enhances the capacity of endometrioma to break down ECM. Higher MMP-9 expression over TIMP-1 expression gives rise to the invasion of endometrioma.