Comparative Effects of Metformin and Dienogest on PI3K/AKT Signaling in Experimental Endometriosis
Abstract
Abstract This study investigates the therapeutic effects of Metformin and Dienogest on the PI3K/AKT signaling pathway in a rat model of induced endometriosis, aiming to enhance treatment strategies. Experimental groups included untreated control rats, rats with surgically induced endometriosis, and treatment groups receiving Dienogest (0.3 mg/kg/day) and Metformin (100 mg/kg/day) for 28 days. Treatments began on the 21st day post-induction and continued until sacrifice on day 49. Uterine cycle was monitored via vaginal smears, and endometrial lesion areas were reassessed pre- and post-treatment. Blood estradiol (E2), progesterone, and VEGF levels were evaluated using enzyme-linked immunosorbent assay (ELISA). The endometriotic implants and uterus were assessed using histopathological analysis. The expression of PI3K/AKT pathway proteins was evaluated in endometriosis lesions and uterine tissue using immunohistochemical and RT-PCR methods. Metformin significantly reduced lesion diameter compared with untreated and dienogest-treated groups (p = 0.002). Serum E2 levels were significantly higher in the metformin group (p = 0.05). Histological examination showed reduced inflammatory infiltration and tissue degeneration in both treatment groups. RT-PCR demonstrated that PI3K, p-PI3K, and AKT expression were increased in the treatment groups within the endometriosis lesions. However, PI3K and p-PI3K expression were found to be reduced in uterine tissue. AKT expression was…
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