The effect of aqueous Stevia rebaudiana extract and clomiphene citrate on the expression of GDF9, PTEN, BMP15 genes, and antioxidant levels in a letrozole-induced polycystic ovary syndrome model in Wistar rats

This study investigates the individual and combined effects of aqueous Stevia rebaudiana extract (SAE) and clomiphene citrate (Clom) on the expression of key ovarian regulatory genes -growth differentiation factor 9 (GDF9), phosphatase and tensin homolog (PTEN), and bone morphogenetic protein 15 (BMP15)- as well as on antioxidant enzyme activities in a letrozole-induced polycystic ovary syndrome (PCOS) model in adult female Wistar rats. The estrous cycles of 50 rats were monitored and randomly divided into five groups of 10 rats each. The control group received carboxymethyl cellulose, while the remaining groups were administered letrozole (1 mg/kg) for 21 days to induce PCOS. From day 22 onward, the treatment groups received SAE (400 mg/kg), Clom (100 mg/kg), or their combination for 28 days. Gene expression levels of GDF9, BMP15, and PTEN were analyzed using real-time PCR, and antioxidant levels were assessed using diagnostic kits. Data were analyzed using SPSS software (version 21) with one-way ANOVA followed by Tukey's post hoc test. Treatments with SAE and Clom restored normal estrous cycles. Significant differences in gene expression were observed: PTEN levels were higher in the control group compared to SAE and combined groups, while GDF9 and BMP15 were elevated in the PCOS group compared to controls. SAE and Clom treatments also significantly increased superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in ovarian tissues. The combined SAE and Clom therapy demonstrate potential as an effective strategy to manage PCOS by regulating ovarian gene expression and oxidative stress.