NAD+ Repletion Rescues Female Fertility during Reproductive Aging
Bertoldo MJ, Listijono DR, Ho WHJ, et al.
Key finding
Oral NMN rescues oocyte quality, meiotic fidelity, and fertility in reproductively aged mice through restoration of ovarian NAD+. Source: Bertoldo MJ, Listijono DR, Ho WHJ, et al. Cell Reports, 2020.
Summary
Mouse study showing that oral NMN supplementation restores oocyte quality and fertility in reproductively aged females. Aged (12-14 month) C57BL/6 mice — a model of human perimenopausal decline — given 2 g/L NMN in drinking water for four weeks showed restored NAD+ in ovarian tissue, reversal of age-associated oocyte meiotic defects (aneuploidy, spindle disorganization), improved fertilization rates, and recovery of litter sizes to near young-adult levels. Mitochondrial function in oocytes normalized, as did the NAD+/NADH ratio. Single-cell metabolomics confirmed that older oocytes from NMN-treated animals resembled those of young controls. The effects were oocyte-specific and did not restore cycle regularity, implicating the NAD+ deficit as an intrinsic gamete problem rather than a whole-reproductive-axis issue. The study is the principal preclinical evidence for ongoing human reproductive-aging trials with NAD+ precursors and is frequently cited in fertility-clinic white-paper claims that run ahead of the human evidence.
For background on the compound studied here, see our NMN precursor reference.
Frequently asked questions
- What did Bertoldo et al. (2020) find about NMN?
- Oral NMN rescues oocyte quality, meiotic fidelity, and fertility in reproductively aged mice through restoration of ovarian NAD+. Source: Bertoldo MJ, Listijono DR, Ho WHJ, et al. "NAD+ Repletion Rescues Female Fertility during Reproductive Aging." Cell Reports, 2020.
- What kind of study is Bertoldo 2020?
- It is a mechanism study on NMN published in Cell Reports in 2020. Mouse study showing that oral NMN supplementation restores oocyte quality and fertility in reproductively aged females. Aged (12-14 month) C57BL/6 mice — a model of human perimenopausal decline — given 2 g/L NMN in drinking water for four weeks showed restored NAD+ in ovarian tissue, reversal of age-associated oocyte meiotic defects (aneuploidy, spindle disorganization), improved fertilization rates, and recovery of litter sizes to near young-adult levels. Mitochondrial function in oocytes normalized, as did the NAD+/NADH ratio. Single-cell metabolomics confirmed that older oocytes from NMN-treated animals resembled those of young controls. The effects were oocyte-specific and did not restore cycle regularity, implicating the NAD+ deficit as an intrinsic gamete problem rather than a whole-reproductive-axis issue. The study is the principal preclinical evidence for ongoing human reproductive-aging trials with NAD+ precursors and is frequently cited in fertility-clinic white-paper claims that run ahead of the human evidence.
- Where can I read the full Bertoldo 2020 paper?
- The primary source is available on PubMed (PMID 32049001) and via DOI 10.1016/j.celrep.2020.01.058.
Access the full paper
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