Cabergoline's Promise in Endometriosis: Restoring Molecular Balance to Improve Reproductive Potential Publisher Pubmed



N Shahgholi NILOOFAR ; Z Noormohammadi ZAHRA ; A Moini ASHRAF ; M Karimipoor MORTEZA
Source: Gynecologic and Obstetric Investigation Published:2025

Abstract

Objectives: Endometriosis is a chronic gynecological condition characterized by abnormal angiogenesis and cell adhesion processes driven by VEGF-VEGFR-2 signaling. cabergoline, a dopamine agonist, has been shown to inhibit angiogenesis in endometriosis. This study investigates the therapeutic potential of cabergoline in modulating these pathways to mitigate endometriotic lesion progression and improve oocyte quality. Design: A randomized, placebo-controlled study was conducted, involving two groups of participants: one receiving cabergoline treatment and the other receiving a placebo. Methods: Eutopic endometrial tissue from women diagnosed with endometriosis was analyzed. VEGFR-2, FAK, PXN, ITGB3, and ITGAV expression levels were measured using qPCR. DNA methylation at the VEGFR-2 promoter was assessed using high-resolution melting analysis to examine epigenetic modifications. Western blot analysis was performed to evaluate the phosphorylation status of tyrosine residue 951 on the VEGFR-2 receptor, which is implicated in cell migration and survival. Oocyte quality was also assessed in both groups. Results: Cabergoline treatment reduced the expression levels of VEGFR-2, FAK, PXN, ITGB3, and ITGAV, with ITGAV showing a statistically significant decrease (p = 0.0174). Hypomethylation of the VEGFR-2 promoter was observed in the treatment group (p = 0.3566). However, phosphorylation of tyrosine residue 951 on VEGFR-2 significantly increased in the cabergoline-treated group (p = 0.004). Notably, oocyte quality significantly improved in the cabergoline group (p = 0.0318). A strong correlation was found between reduced VEGFR-2 expression (p = 0.0184), decreased promoter methylation (p = 0.0159), and downregulation of PTK2 expression (p = 0.0057), all of which are associated with improved oocyte quality. Limitations: The sample size was limited, and additional long-term studies are needed to confirm the therapeutic potential of cabergoline in endometriosis treatment. Conclusions: Cabergoline may enhance oocyte quality by modulating key regulators of the angiogenic pathway. These findings suggest its potential role in the management of endometriosis-related infertility, warranting further clinical investigation. © 2025 Elsevier B.V., All rights reserved.