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Sodium dehydroacetate induces porcine oocyte toxicity by inhibiting TCA cycle activity and mitochondrial function, with nicotinamide mononucleotide as a potential protective agent

文献类型： 外文期刊

作者： Li, Na 1 ; Li, Yu 1 ; Huang, Guangjun 1 ; Sun, Hongyu 1 ; Wu, Jiaqi 1 ; Gao, Qian 2 ; Cui, Zhaokang 3 ; Miao, Yilong 1 ;

作者机构： 1.Nanjing Agr Univ, Coll Anim Sci & Technol, Nanjing 210095, Peoples R China

2.Nanjing Agr Univ, Coll Vet Med, Nanjing 210095, Peoples R China

3.Jiangsu Acad Agr Sci, Inst Anim Sci, Nanjing 210014, Peoples R China

关键词： Na-DHA; Oocyte; Metabolomics; NMN; Mitochondria

期刊名称：FOOD AND CHEMICAL TOXICOLOGY （ 影响因子：3.5； 五年影响因子：4.1 ）

ISSN： 0278-6915

年卷期： 2025 年 203 卷

页码：

收录情况： SCI

摘要： 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 alpha-ketoglutarate dehydrogenase (alpha-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 alpha-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.

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