Cerium oxide nanoparticles protect against obesity-induced ovarian dysfunction

Abstract Maternal obesity results in metabolic disorders and increases oxidative stress, leading to gradual declines in ovarian functions and oocyte quality. However, strategies to improve these are still lacking. Here, we found that cerium oxide nanoparticles (CeO2 NPs) with intrinsic antioxidant properties could protect against high fat diet (HFD)-induced oocyte dysfunction in mice. Administration of CeO2 NPs to mice fed a HFD attenuated serum lipid accumulation, dyslipidemia, glucose intolerance, and insulin resistance. Supplementation with CeO2 NPs improved oocyte mitochondrial functions and decreased endoplasmic reticulum (ER) stress, as well as decreasing HFD-induced communications between mitochondria and the ER with the formation of mitochondria-associated ER membranes in the ovaries of HFD-fed mice. Furthermore, for the first time, we found that oocyte quality was improved in CeO2 NPs-treated HFD-fed mice as reflected by decreased reactive oxygen species levels and fewer abnormal spindles, accompanied by improved potential for early embryonic development. Thus, treatment with CeO2 NPs could protect against HFD-induced deterioration of ovarian functions and oocyte quality, providing the basis for potential clinical applications to alleviate the decreased oocyte quality associated with maternal obesity.