Effect of ovulation induction on PI3K/AKT signaling pathway and miRNA expression in rats with polycystic ovarian syndrome

Polycystic ovary syndrome (PCOS) is characterized by metabolic disorders that affect 4-21% of women of reproductive age and is a cause of infertility. Altered miRNA expression contributes to cervical cancer, endometriosis, poor ovarian response and cardiovascular disease. Therefore, some miRNAs have been found to be novel biomarkers for abnormal metabolism, impaired oocyte quality and reduced endometrial receptivity in PCOS. The aim of this study was to investigate the effect of ovulation induction on PI3K-Akt signaling pathway and miRNA expression in PCOS patients. 28 Sprague Dawley adult female rats were randomly divided into 3 groups. The control group received only 0.9% isotonic 0.9% soydum chloride (1mg/kg) by gavage for 25 days, while PCOS and PCOS+Ovulation induction (PCOS+OI) groups received Letrozole at a dose of 1mg/kg by gavage for 25 days. For ovulation induction, superovulation was performed by intraperitoneal injection of 150-300 IU/kg pregnant mare serum gonadotropin on the 25th day. After 48 hours, 150-300 IU/kg human chorionic gonadotropin (hCG) was given intraperitoneally. Blood FSH, estrogen and testosterone levels were analyzed by ELISA method. Ovarian tissues were evaluated histopathologically. PI3K/AKT pathway was evaluated immunohistochemically and miRNA-451a, miRNA-33b-5p, miRNA-378a-5p, miRNA-486-5p, miRNA-140, miRNA-320a expressions were determined by RT-PCR method. In our study, vaginal smear findings and blood hormone levels showed that we created an experimental PCOS model. Ovulation induction further increased T and E2 levels and decreased FSH levels significantly compared to the control group (p<0.05). In miRNA analysis, miR-140, 451 and 378 expression decreased and miR-451 increased significantly in PCOS+OI group (p<0.05). As a result of immunohistochemical analysis, PI3K, AKT, p-PI3K, p-AKT expressions showed statistically significant positive reaction in PCOS+OI group compared to PCOS group. Ovulation induction activated PI3K/AKT signaling pathway by decreasing miR-140, 378 and 451 expression and increasing miR-451 expression in PCOS experimental rat model. Activation of this pathway inhibited granulosa cell apoptosis and autophagic cell death and helped prevent follicular atresia. These results not only help to understand the pathogenesis of PCOS, but may also provide a new direction for the treatment of PCOS patients with infertility.