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.