Sirtuin 3-mediated deacetylation of superoxide dismutase 2 ameliorates sodium fluoride-induced mitochondrial dysfunction in porcine oocytes

Fluoride exerts detrimental effects on germ cells and increases the infertility rate in women. Nevertheless, the precise mechanisms behind the developmental abnormalities caused by fluoride in oocytes remain poorly comprehended. The current study, we established mitochondrial damage model in oocytes via 50 mu g/mL sodium fluoride (NaF) supplementation. We then examined the effects of honokiol in preventing mitochondrial deficits caused by NaF and investigated the mechanisms through which honokiol protects oocytes. The findings investigated that NaF increased levels of mitochondrial reactive oxygen species (mtROS) and hindered mitochondrial function, as evidenced by the dissipation of mitochondrial membrane potential, abnormal expression of mitochondrial DNA copy numbers, and mtDNA harm in oocytes. mtROS scavenging using Mito-TEMPO alleviated oxidative damage in mitochondria and restored the oocyte developmental competence. Superoxide dismutase 2 (SOD2) acetylation was significantly increased, whereas sirtuin 3 (SIRT3) expression was decreased in NaF-treated oocytes. The addition of honokiol helped in the deacetylation of SOD2 at K122 through SIRT3, resulting in the removal of excessive mtROS and the recovery of mitochondrial function. Therefore, SIRT3/SOD2 pathway aids honokiol in mitigating fluoride-induced mitochondrial dysfunction. Overall, honokiol improved the mitochondrial harm caused by NaF by controlling mtROS and mitochondrial function, with the SIRT3/SOD2 pathway having an important function. These findings suggest honokiol as a potential therapeutic strategy for NaF-induced oocyte development and mitochondrial deficits.