Betaine alleviates letrozole-induced polycystic ovarian syndrome in rats by regulating oxidative stress and inflammation and restoring the proliferation-apoptosis balance

BACKGROUND: Polycystic ovarian syndrome (PCOS) is a common reproductive disorder that often leads to infertility. This study aimed to examine the potential beneficial effects of betaine (BTN) in a rat model of letrozole-induced PCOS. METHODS: Thirty-six adult female rats were allocated to six groups (n = 6): control, BTN 100 (100 mg/kg/day BTN), PCOS (1 mg/kg/day letrozole), PCOS + BTN 50 (1 mg/kg/day letrozole + 50 mg/kg/day BTN), PCOS + BTN 100 (1 mg/kg/day letrozole + 100 mg/kg/day BTN), and PCOS + Metformin (Met) (1 mg/kg/day letrozole + 300 mg/kg/day Met). Letrozole was administered orally for 21 days, followed by 14 days of oral BTN or Met treatment. RESULTS: Our findings indicated that BTN significantly ameliorated fasting blood glucose levels, insulin resistance, ovarian histopathological changes, and fibrosis in rats with PCOS. Reduced follicle-stimulating hormone (FSH) concentration, elevated luteinizing hormone (LH) levels, and an increased LH/FSH ratio were all alleviated in the BTN-treated PCOS rats. Moreover, BTN significantly diminished ovarian oxidative stress, as evidenced by elevated catalase and glutathione peroxidase activities, upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) expression, and reduced malondialdehyde levels. Betaine markedly suppressed PCOS-induced inflammation by downregulating phosphorylated p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor-kappa B p65 (NF-κB p65). The disrupted proliferation-apoptosis balance was notably restored following BTN treatment through the regulation of p53, cleaved caspase-3, B-cell lymphoma 2 (Bcl2), and proliferating cell nuclear antigen (PCNA). Interestingly, the beneficial effects of 100 mg/kg BTN were more pronounced than those of 50 mg/kg BTN or Met. CONCLUSIONS: This study elucidated the effectiveness of BTN in ameliorating letrozole-induced PCOS in rats by reducing oxidative stress, apoptosis, and inflammation, and modulating PCNA.