Impaired Expression of Membrane Type-2 and Type-3 Matrix Metalloproteinases in Endometriosis but Not in Adenomyosis
Jane B Maoga1, Muhammad A Riaz1, Agnes N Mwaura1
1Department of Gynecology and Obstetrics, Justus Liebig University, 35392 Giessen, Germany.
Abstract:
Matrix metalloproteinases (MMPs) play an important role in menstruation and endometriosis; however, the membrane-type matrix metalloproteinases (MT-MMPs) are not well studied in endometriosis and adenomyosis. We analyzed MT2-MMP (MMP15) and MT3-MMP (MMP16) in eutopic endometrium with and without endometriosis and with and without adenomyosis and ectopic endometrium of deep infiltrating endometriosis (DIE), peritoneal endometriosis (PE), and ovarian endometriosis (Ov) by immunohistochemistry. Preferential expression of both proteins was observed in the glandular and luminal epithelial cells of the eutopic endometrium of patients with and without endometriosis with a ~2.5-fold stronger expression of MT3-MMP compared to MT2-MMP. We did not observe any differences during menstrual cycling and in eutopic endometrium of patients with and without endometriosis. Similarly, eutopic endometrium and adenomyotic tissue with and without endometriosis showed similar protein levels of MT2-MMP and MT3-MMP. In contrast, MT2-MMP and MT3-MMP protein was decreased in ectopic compared to eutopic endometrium and adenomyosis. The similar expression of MT2-MMP and MT3-MMP in eutopic endometrium in patients with and without endometriosis in contrast to the impaired expression in ectopic endometrium suggests that alterations occur after and not before endometrial implantation possibly by distinct interactions with the different environments. The differential protein expression of MT2/3-MMP in adenomyosis compared to endometriosis might suggest a different pathogenesis pathway for the two diseases.
Insights
Membrane-type matrix metalloproteinases (MT-MMPs), specifically MT2-MMP and MT3-MMP, are decreased in ectopic endometrial tissue, suggesting alterations occur after implantation in endometriosis and adenomyosis.
Area of Science:
- Gynecology
- Molecular Biology
- Oncology
Background:
- Matrix metalloproteinases (MMPs) are crucial in endometrial processes.
- Membrane-type MMPs (MT-MMPs) roles in endometriosis and adenomyosis remain understudied.
- MT2-MMP (MMP15) and MT3-MMP (MMP16) are key MT-MMPs.
Purpose of the Study:
- To investigate the expression of MT2-MMP and MT3-MMP in endometriosis and adenomyosis.
- To compare MT-MMP levels in eutopic endometrium, adenomyotic tissue, and ectopic endometrial lesions.
- To explore the potential role of MT-MMPs in the pathogenesis of these conditions.
Main Methods:
- Immunohistochemistry was used to analyze MT2-MMP and MT3-MMP protein expression.
- Samples included eutopic endometrium (with/without endometriosis/adenomyosis) and ectopic tissues (DIE, PE, Ov).
- Expression levels were compared across different tissue types and disease states.
Main Results:
- MT2-MMP and MT3-MMP were preferentially expressed in glandular and luminal epithelial cells of eutopic endometrium.
- MT3-MMP expression was approximately 2.5-fold higher than MT2-MMP in eutopic endometrium.
- No significant differences in MT-MMP expression were found in eutopic endometrium during the menstrual cycle or between patients with/without endometriosis or adenomyosis.
- MT2-MMP and MT3-MMP protein levels were decreased in ectopic endometrial tissues compared to eutopic endometrium and adenomyosis.
- Differential expression of MT2/3-MMP in adenomyosis versus endometriosis suggests distinct pathogenic pathways.
Conclusions:
- Impaired expression of MT2-MMP and MT3-MMP in ectopic endometrium suggests alterations occur post-implantation.
- Distinct interactions with different microenvironments may influence MT-MMP expression in ectopic lesions.
- Differential MT2/3-MMP expression patterns may indicate different pathogenesis pathways for endometriosis and adenomyosis.
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