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NMN supplementation improves oocyte mitochondrial function and oxidative stress regulation, aligning with NAD⁺-dependent gene expression changes during human oocyte maturation.
Declining oocyte quality remains a key biological barrier to female fertility, particularly with advancing age and metabolic stress. New research indicates that nicotinamide mononucleotide (NMN)—a key precursor of nicotinamide adenine dinucleotide (NAD⁺)—may help counter this decline by restoring mitochondrial function and cellular energy balance in oocytes.
Investigators conducted a systematic review in accordance with PRISMA guidelines, analyzing studies published across Medline, Embase, and Scopus. After rigorous screening and risk-of-bias assessment, 7 high-quality preclinical studies were incorporated. Findings were synthesized via thematic and pathway-based analyses. To assess human relevance, investigators additionally performed single-oocyte RNA sequencing on 46 human oocytes obtained at the germinal vesicle, metaphase I, and metaphase II stages, enabling detailed evaluation of NAD⁺-dependent and mitochondrial gene expression during oocyte maturation.
Across diverse animal models, NMN supplementation consistently improved oocyte-associated cellular processes, including:
Human transcriptomic profiling identified 900 differentially expressed genes between immature and mature oocytes. Critically, genes central to mitochondrial dynamics and oxidative stress regulation—including sirtuin 3 (SIRT3), dynamin 1-like protein (DNM1L), and superoxide dismutase 1 (SOD1)—exhibited substantial expression shifts, closely aligning with the known molecular actions of NMN and NAD⁺ metabolism.
The integration of preclinical and human transcriptomic data underscores mitochondrial and redox pathways as key regulatory checkpoints in oocyte maturation. These findings strengthen the biological rationale for targeting NAD⁺ metabolism as a novel approach to preserving oocyte quality and extending reproductive lifespan. While the evidence is encouraging, researchers caution that standardized dosing protocols, safety evaluations, and well-designed trials are fundamental before NMN can be advocated in fertility care.
Journal of Assisted Reproduction and Genetics
NMN supplementation as a strategy to improve oocyte quality: a systematic review and transcriptomic analysis
Hyunseo Noh et al.
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