Sodium dehydroacetate induces porcine oocyte toxicity by inhibiting TCA cycle activity and mitochondrial function,...

Sodium dehydroacetate (Na-DHA), a widely used antimicrobial food additive, raises bioaccumulation and organ toxicity concerns, with female reproductive effects remaining understudied. This study investigates Na-DHA's impact on porcine oocyte maturation and evaluates nicotinamide mononucleotide (NMN) as a protective agent. Na-DHA exposure impaired oocyte maturation, suppressing first polar body extrusion and cumulus expansion. Metabolomic analysis revealed disrupted energy metabolism via tricarboxylic acid (TCA) cycle inhibition, notably reducing succinate and fumarate levels. Molecular docking confirmed Na-DHA competitively binds α-ketoglutarate dehydrogenase (α-KGDH), a key TCA enzyme, impairing mitochondrial ATP synthesis and elevating oxidative stress. These metabolic defects induced cytoskeletal abnormalities (spindle disorganization, actin disruption, cortical granule mislocalization), reducing fertilization rates and compromising blastocyst development. NMN supplementation restored mitochondrial function, mitigated oxidative stress and apoptosis, and rescued meiotic progression, enhancing embryonic outcomes. The findings elucidate Na-DHA's reproductive toxicity via α-KGDH-mediated TCA cycle suppression and mitochondrial dysfunction, while demonstrating NMN's protective role through NAD⁺-dependent metabolic homeostasis. This study highlights Na-DHA's risks to oocyte quality and proposes NMN as a potential therapeutic strategy to counteract food additive-induced reproductive damage.