Tier 3 — preclinical

NAD+ Repletion Rescues Female Fertility during Reproductive Aging

Michael J Bertoldo, Dave R Listijono, Wing-Hong Jonathan Ho, Angelique H Riepsamen, Dale M Goss, Dulama Richani, Xing L Jin, Saabah Mahbub, Jared M Campbell, Abbas Habibalahi, Wei-Guo Nicholas Loh, Neil A Youngson, Jayanthi Maniam, Ashley S A Wong, Kaisa Selesniemi, Sonia Bustamante, Catherine Li, Yiqing Zhao, Maria B Marinova, Lynn-Jee Kim, Laurin Lau, Rachael M Wu, A Stefanie Mikolaizak, Toshiyuki Araki, David G Le Couteur, Nigel Turner, Margaret J Morris, Kirsty A Walters, Ewa Goldys, Christopher O'Neill, Robert B Gilchrist, David A Sinclair, Hayden A Homer, Lindsay E Wu
Cell Reports 2020 30(6):1670-1681.e7

Bibliography

PubMed
PMID 32049001
PubMed Central
PMC7063679
DOI
10.1016/j.celrep.2020.01.058
Funding
Supported by Australian NHMRC and ARC grants. Salary and experimental costs for some investigators were partly supported by sponsored research contracts from Jumpstart Fertility to UNSW.
Competing interests
Several senior authors were cofounders, shareholders, directors or advisers of Jumpstart Fertility, were inventors on fertility-related patents licensed to the company, or had related commercial interests; the article discloses these relationships in detail.

Study snapshot

DesignControlled preclinical reproductive-aging experiments combining NMN treatment, oocyte/embryo assays and genetic manipulation of NAD-related pathways.
ModelAged female mice, isolated oocytes and developing embryos.
SampleMultiple mouse and oocyte cohorts across experiments; not a human participant study.
InterventionNMN administered to aged female mice, including approximately 2 g/L in drinking water for selected experiments and acute dosing paradigms; embryo media experiments also tested NMN exposure.
DurationVaried by experiment; key aging interventions included several weeks of NMN exposure.
EndpointsOocyte NAD(P)H; Oocyte quality; Fertility; Ovulation; Embryo development; SIRT2 signaling; Reproductive aging

What the study showed, in plain terms

This influential 2020 study found that NAD-related metabolism declines in aging oocytes and that NMN treatment could improve oocyte quality and restore fertility measures in aged mice.

The work also reported improvements in embryo-development milestones and used genetic experiments to probe whether SIRT2 mediated the effect.

It is often cited in discussions of NMN and female fertility, but the crucial limitation is straightforward: these were mouse and laboratory experiments, not a human fertility trial.

Key findings

  • Age-related oocyte dysfunction was associated with declining NAD(P)H.
  • NMN treatment improved oocyte quality and fertility outcomes in aged mice.
  • Embryo developmental milestones improved in selected NMN experiments.
  • SIRT2 overexpression mimicked some benefits, although SIRT2 deletion did not eliminate oocyte quality.
  • The authors framed NAD+ restoration as a potential reproductive-aging strategy requiring translation to humans.

What this study can and cannot tell us

No women were treated with NMN in this study, so it cannot establish effects on ovarian reserve, egg quality, IVF success, pregnancy rate or live birth in humans.

The study has notable disclosed commercial interests related to fertility applications of NAD+ restoration, which should be considered when interpreting translational claims.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology