MMP2/TIMP2 ratio as a measurable indicator for differentiating diffuse adenomyosis, ovarian endometriosis, and their...

Adenomyosis and endometriosis, two common estrogen-dependent benign gynecological disorders usually present with overlapping symptoms, such as pain and infertility. These two conditions often co-exist and are associated with poor reproductive outcome. Both adenomyosis and endometriosis are associated with extracellular matrix (ECM) remodeling, regulated by matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). MMP2/TIMP2 balance is known to be crucial for endometrial ECM homeostasis. This study, for the first time, compares MMP2 and TIMP2 activity in adenomyosis, endometriosis, co-existent adenomyosis-endometriosis and controls. Women (26-39 years) awaiting IVF at the Institute of Reproductive Medicine, Kolkata, India were classified into four groups: diffuse adenomyosis (n = 20), ovarian endometriosis (n = 20), co-existent diffuse adenomyosis-ovarian endometriosis (n = 17), and controls (n = 20). The gene and protein expressions of MMP2 and TIMP2 in eutopic endometrium were assessed using quantitative reverse-transcriptase PCR and western blot, respectively. We observed decreased MMP2 expression in adenomyosis, endometriosis and the co-existent group, suggesting its central role in the fibrotic remodeling processes. MMP2/TIMP2 ratio, a known regulator of ECM turnover, was observed to be significantly higher in adenomyosis, indicating relatively aggressive ECM remodeling over endometriosis. TIMP2 expression was maximum in endometriosis and emerged as the key player in substantially lowering the ratio. Also, MMP2/TIMP2 ratio positively correlated with both BMI and uterine volume in adenomyosis. Unlike adenomyosis or endometriosis, the co-existent group displayed a distinct MMP2 and TIMP2 profile, warranting further investigation. We hope that our findings will encourage researchers to explore the feasibility of MMP2/TIMP2 ratio in evaluating adenomyosis and endometriosis.