The activity of Matrix Metalloproteinase-2 (MMP-2) and Tissue Inhibitors of Metalloproteinase-2 (TIMP-2) that are associated with the degree of endometrioma tissue invasion transplanted onto the Chorioallantoic Membrane (CAM)

Background: One of the fundamental pathogenesis of endometriosis to grow and develop is to carry out a cellular invasion of the surrounding tissue where it attaches. The invasion process of endometriotic focus is linked with the activity of matrix metalloproteinases-2 (MMP-2) and tissue inhibitors of metalloproteinases-2 (TIMP-2). In this study, we used endometrioma tissue to be implanted in chick chorioallantoic membrane (CAM) as a medium culture model to reconstruct and evaluate the invasion process of endometriosis. Then the MMP-2, TIMP-2 and invasion pattern can be invitro observed. Methods: Endometrioma tissue fragments were taken from ovarian endometrioma patients, reproductive age, no medication and no malignancy who underwent laparoscopic surgery. Sample research was taken in consecutive and non-probability sampling. The tissue fragments were divided into 4-8 strips, each dimension of 2 x 2 mm2. Two strips were assessed for the activity of MMP-2. Two remaining strips were transplanted onto the CAM. After incubation for five days, the transplanted tissues were harvested for assessment of MMP-2 by gelatin zymography, TIMP-2 by western blot and histological assessment by hematoxylin-eosin staining. The assessment was carried out by two qualified biologists as an observer. Result: Twenty-four fragments of endometrioma have been collected from 24 endometrioma patients who underwent laparoscopy surgery. The average age was 31±5 years, the BMI was 22±3 kg/m2, the duration of infertility was 58 ± 3 months, and r-ASRM was 67±35. In CAM of transplanted endometriomas tissue, MMP-2 activity was positively correlated with TIMP-2 in a moderate relationship (rτ = 0.56, p-value < 0.05), very weak positive correlation with invasion level (rτ = 0.08, p-value >0.05). TIMP-2 expression was negatively correlated with invasion level in a strong relationship (rτ =-0.35, p-value <0.05). The ratio between MMP-2/TIMP-2 was positively correlated with invasion level in a very strong relationship (rτ = 0.72, p-value < 0.05). ICC (intraclass correlation coefficient) value was 0.96, and p-value= 0.01, CI 95. It shows that there was high reliability between observers. Conclusion: The invasion level of endometrioma transplanted onto CAM was determined by the balance between MMP-2 and TIMP-2. © 2023, Sanglah General Hospital. All rights reserved.