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HIGH EXPRESSION OF TRANSFORMING GROWTH FACTOR β-1 (TGF β-1) AND MATRIX METALOPROTEINASE-9 (MMP-9) IN THE SACROUTERINE LIGAMENTUM AS A RISK FACTOR FOR THE OCCURRING OF GRADE III-IV UTERINE PROLAPS

Alit Darma Asmara, I Wayan Megadhana, I Gede Mega Putra, Putu Doster Mahayasa, I Nyoman Hariyasa Sanjaya, Made Darmayasa

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ABSTRACT

 

Background: The incidence of pelvic organ prolapse increases with age. A retrospective study in a gynecology clinic at a hospital in Denpasar reported a prevalence of pelvic organ prolapse of 11.38%, over a period of 2 years. One type of TGF-β that influences the remodeling process in the sacrouterine ligament is TGF-β1. TGF-β1 controls collagen synthesis and degradation in pelvic connective tissue by stimulating tissue inhibitor of metalloproteinase (TIMP) synthesis and inhibiting MMP activity. MMP-9 is secreted by a large number of cell types, including neutrophils, macrophages, and fibroblasts. MMP-9 is thought to be related to cell migration, invasion and tissue remodeling in the reproductive process. This research is to prove the expression of Transforming Growth Factor Beta 1 (TGF- β1) and high expression of Matrix Metalloproteinase-9 (MMP-9) as risk factors for grade III-IV uterine prolapse..

Method: This type of research is research that uses an analytical observational design with case control. The case was a patient with grade III-IV uterine prolapse who had undergone a total vaginal hysterectomy. Controls were non-uterine prolapse patients who had undergone total hysterectomy for indications of benign abnormalities such as uterine myoma or bleeding disorders. Each group was then divided into high and low TGF-β1 and MMP-9 expression.

Results: In this study, high TGF-β1 expression was more frequently found in sacrouterine ligament samples from women who experienced uterine prolapse compared to women who did not experience uterine prolapse. The results showed that high TGF-β1 expression in the sacrouterine ligament significantly increased the risk factor for grade III-IV uterine prolapse up to 14.00-fold (OR 14.00; 95% CI 2.370 – 82.717; p=0.004). This study also showed that high MMP-9 expression in the sacrouterine ligament significantly increased the risk factor for grade III-IV uterine prolapse up to 8,867-fold (OR 8.867; 95% CI 2.246–34.998; p=0.002).

Conclusion: High expression of TGF-β1 and MMP-9 is a risk factor for grade III-IV uterine prolapse.

Keywords: Prolapse, Transforming Growth Factor, Matrix Metaproteinas