Activation of NLRP3 inflammasome in the ovaries during the development and treatment of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is considered as a highly heterogeneous and complex disease. Dimethyldiguanide (DMBG) is widely used to improve the reproductive dysfunction in women with PCOS. However, the precise mechanism by which DMBG exerts its benefical effect on PCOS remains largely unknown. The present study was designed to explore the effects of DMBG on the changes of oxidative stress and the activation of nucleotide leukin rich polypeptide 3 (NLRP3) inflammasome in the ovaries during the development and treatment of PCOS. A letrozole-induced rat PCOS model was developed. The inflammatory status was examined by analyzing the serum high sensitive C-reactive protein (hsCRP) levels in ras. We found that DMBG treatment rescued PCOS rats, which is associated with the reduced chronic low grade inflammation in these rats. In PCOS rats, the NLRP3 and the adaptor protein apoptosis-associated speck-like protein (ASC) mRNA levels, caspase-1 activation, and IL-1β production were unregulated, which was markedly attenuated by DMBG treatment. Moreover, oxidative stress was enhanced in PCOS rats as shown by increased lipid peroxidation (LPO) and activity of superoxide dismutase (SOD) and catalase. DMBG significantly decreased LPO, while it had no effects on SOD and catalase activities. Together, these results indicate that DMBG treatment may rescue PCOS rats by suppressing oxidative stress and NLRP3 inflammasome activation in PCOS ovaries.