Fertility protection during chemotherapy treatment by boosting the NAD(P)+ metabolome
Chemotherapy induced ovarian failure and infertility is an important concern in female cancer patients of reproductive age or younger, and non-invasive, pharmacological approaches to maintain ovarian function are urgently needed. Given the role of reduced nicotinamide adenine dinucleotide phosphate (NADPH) as an essential cofactor for drug detoxification, we sought to test whether boosting the NAD(P)<sup>+</sup> metabolome could protect ovarian function. We show that pharmacological or transgenic strategies to replenish the NAD<sup>+</sup> metabolome ameliorates chemotherapy induced female infertility in mice, as measured by oocyte yield, follicle health, and functional breeding trials. Importantly, treatment of a triple-negative breast cancer mouse model with the NAD<sup>+</sup> precursor nicotinamide mononucleotide (NMN) reduced tumour growth and did not impair the efficacy of chemotherapy drugs in vivo or in diverse cancer cell lines. Overall, these findings raise the possibility that NAD<sup>+</sup> precursors could be a non-invasive strategy for maintaining ovarian function in cancer patients, with potential benefits in cancer therapy.
Authors
- Michael J. Bertoldo (ORCID: https://orcid.org/0000-0002-9471-501X)
- Hayden Homer (ORCID: https://orcid.org/0000-0002-3104-0449)
- Derek Wong (ORCID: https://orcid.org/0000-0003-2607-5265)
- Wing-Hong Jonathan Ho
- Dale M. Goss (ORCID: https://orcid.org/0000-0002-8356-1617)
- Lynn‐Jee Kim
- Robert B. Gilchrist (ORCID: https://orcid.org/0000-0003-1611-7142)
- Angelique H. Riepsamen (ORCID: https://orcid.org/0000-0002-7633-6294)
- Dulama Richani (ORCID: https://orcid.org/0000-0003-1886-0423)
- Nigel Turner (ORCID: https://orcid.org/0000-0002-0119-9328)
- Maria B. Marinova
- David Sinclair (ORCID: https://orcid.org/0000-0002-9936-436X)
- Dave R. Listijono (ORCID: https://orcid.org/0000-0002-7159-9589)
- Kirsty A. Walters (ORCID: https://orcid.org/0000-0002-1504-9734)
- Sonia Bustamante (ORCID: https://orcid.org/0000-0002-5411-2919)
- Kaisa Selesniemi
- Romanthi J. Madawala (ORCID: https://orcid.org/0000-0002-6560-8389)
- Lindsay E. Wu (ORCID: https://orcid.org/0000-0002-1599-7574)
- Toshiyuki Araki (ORCID: https://orcid.org/0000-0003-3625-2042)
- Emily R. Frost (ORCID: https://orcid.org/0000-0001-8696-2136)
- Safaa Cabot
- Ling Zhong (ORCID: https://orcid.org/0000-0003-3657-4092)
- Catherine Li (ORCID: https://orcid.org/0000-0002-1579-649X)
- David J. Livingston
- María Marchante
- Amelia Brown
Institutions
- Harvard University (US)
- Universitat de València (ES)
- Victor Chang Cardiac Research Institute (AU)
- Royal Brisbane and Women's Hospital (AU)
- UNSW Sydney (AU)
- St Vincent's Hospital Melbourne (AU)
- ECI Biotech (United States) (US)
- Valencian Infertility Institute (ES)
- National Center of Neurology and Psychiatry (JP)
- The Kinghorn Cancer Centre (AU)
Publication Details
- Journal
- EMBO Molecular Medicine
- Published
- 2024-08-21
- DOI
- https://doi.org/10.1038/s44321-024-00119-w
- Citations
- 12
- Primary Topic
- Reproductive Biology and Fertility
- Type
- article
- Field-Weighted Citation Impact
- 6.52
Funders
- American Federation for Aging Research
- National Imaging Facility
- Analytical Center for the Government of the Russian Federation
- University of New South Wales
- Medical Research Council
- National Health and Medical Research Council