Hashimoto Shu, Gamage Udayanga, Inoue Yuki, Iwata Hisataka, Morimoto Yoshiharu
Graduate School of Medicine, Osaka Metropolitan University, Osaka, 545-8585, Japan.
HORAC Grand Front Osaka Clinic, Osaka, 530-0011, Japan.
Sci Rep. 2025 Jan 2;15(1):310. doi: 10.1038/s41598-024-81393-z.
Nicotinamide adenine dinucleotide (NAD(H)) and its metabolites function as crucial regulators of physiological processes, allowing cells to adapt to environmental changes such as nutritional deficiencies, genotoxic factors, disruptions in circadian rhythms, infections, inflammation, and exogenous substances. Here, we investigated whether elevated NAD(H) levels in oocytes enhance their quality and improve developmental competence following in vitro fertilization (IVF). Bovine cumulus-oocyte complexes (COCs) were matured in a culture medium supplemented with 0-100 μM nicotinamide mononucleotide (NMN), a precursor of NAD(H). The addition of NMN caused an increase in intracellular NAD(H) and nicotinamide adenine dinucleotide phosphate levels, leading to enhanced competence for development to the blastocyst stage after IVF. The increase in intracellular NAD(H) levels led to changes in the expression of mitochondria function-related genes. As a result, NMN supplementation increased the ratio of MitoTracker Orange fluorescence to nonyl acridine orange fluorescence, as well as adenosine triphosphate levels, while decreasing reactive oxygen species levels in the oocytes. NMN also lowered chromosome lagging during anaphase. These results suggest that increased NAD(H) levels in oocytes following NMN treatment enhances post-fertilization developmental competence through improved mitochondrial function.
烟酰胺腺嘌呤二核苷酸(NAD(H))及其代谢产物作为生理过程的关键调节因子,使细胞能够适应环境变化,如营养缺乏、遗传毒性因素、昼夜节律紊乱、感染、炎症和外源性物质。在此,我们研究了卵母细胞中升高的NAD(H)水平是否能提高其质量,并改善体外受精(IVF)后的发育能力。牛卵丘-卵母细胞复合体(COCs)在添加了0-100μM烟酰胺单核苷酸(NMN,NAD(H)的前体)的培养基中成熟。添加NMN导致细胞内NAD(H)和烟酰胺腺嘌呤二核苷酸磷酸水平增加,从而提高了IVF后发育至囊胚阶段的能力。细胞内NAD(H)水平的增加导致线粒体功能相关基因表达的变化。结果,补充NMN增加了卵母细胞中MitoTracker Orange荧光与壬基吖啶橙荧光的比率以及三磷酸腺苷水平,同时降低了活性氧水平。NMN还减少了后期染色体滞后现象。这些结果表明,NMN处理后卵母细胞中NAD(H)水平的增加通过改善线粒体功能增强了受精后的发育能力。