The Impact of Ghrelin on Intrauterine Adhesions: Insights from Experimental Models

This study aimed to evaluate the therapeutic effects of ghrelin, a 28-amino acid peptide hormone with immunomodulatory, anti-inflammatory, antifibrotic, and antioxidant properties, on intrauterine adhesions (IUA) in a rat model. Twenty-eight adult female rats were divided into four groups: control, IUA model, low-dose ghrelin (20 ng/kg), and high-dose ghrelin (40 ng/kg). IUA was induced using 0.2 ml of trichloroacetic acid (TCA) injected into the right uterine horn. After three estrous cycles, rats received ghrelin injections under radiological guidance into the uterine cavity for seven days. Uterine tissues were collected for histological examination and immunohistochemical analysis targeting markers such as vascular endothelial growth factor (VEGF), type 1 collagen, tumor necrosis factor-alpha (TNFα), fibroblast growth factor 2 (FGF2), and hypoxia-inducible factor 1-alpha (HIF-1α). Ghrelin administration resulted in significant weight gain starting from day 5 (p < 0.001). The IUA group exhibited the lowest uterine wall thickness, which improved dose-dependently with ghrelin treatment (p < 0.001). Histopathological findings in the IUA group included epithelial degeneration, lumen narrowing, inflammation, fibrosis, and glandular atrophy, all of which were reversed with ghrelin. Immunohistochemical analysis showed the highest expression of type 1 collagen, TNFα, HIF-1α, and FGF2 in the IUA group, which decreased dose-dependently with ghrelin (p < 0.001). Conversely, VEGF expression, which was lowest in the IUA group, increased significantly with ghrelin administration in a dose-dependent manner. Ghrelin demonstrated favorable therapeutic effects in reversing histological and molecular alterations associated with intrauterine adhesions. These findings suggest that ghrelin may represent a promising candidate for IUA treatment, warranting further experimental and clinical investigation.