Fertility protection during chemotherapy treatment by boosting the NAD(P) + metabolome.

Autor:	Ho WJ; School of Biomedical Sciences, UNSW Sydney, Kensington, NSW, 2052, Australia.; School of Clinical Medicine, UNSW Sydney, Kensington, NSW, 2052, Australia.; The Kinghorn Cancer Centre, St. Vincent's Hospital, Darlinghurst, NSW, Australia., Marinova MB; School of Biomedical Sciences, UNSW Sydney, Kensington, NSW, 2052, Australia.; School of Clinical Medicine, UNSW Sydney, Kensington, NSW, 2052, Australia., Listijono DR; School of Biomedical Sciences, UNSW Sydney, Kensington, NSW, 2052, Australia.; School of Clinical Medicine, UNSW Sydney, Kensington, NSW, 2052, Australia., Bertoldo MJ; School of Biomedical Sciences, UNSW Sydney, Kensington, NSW, 2052, Australia.; School of Clinical Medicine, UNSW Sydney, Kensington, NSW, 2052, Australia., Richani D; School of Clinical Medicine, UNSW Sydney, Kensington, NSW, 2052, Australia., Kim LJ; School of Biomedical Sciences, UNSW Sydney, Kensington, NSW, 2052, Australia., Brown A; School of Clinical Medicine, UNSW Sydney, Kensington, NSW, 2052, Australia., Riepsamen AH; School of Clinical Medicine, UNSW Sydney, Kensington, NSW, 2052, Australia., Cabot S; School of Biomedical Sciences, UNSW Sydney, Kensington, NSW, 2052, Australia., Frost ER; School of Clinical Medicine, UNSW Sydney, Kensington, NSW, 2052, Australia., Bustamante S; Bioanalytical Mass Spectrometry Facility, Mark Wainwright Analytical Centre, UNSW Sydney, Kensington, NSW, 2052, Australia., Zhong L; Bioanalytical Mass Spectrometry Facility, Mark Wainwright Analytical Centre, UNSW Sydney, Kensington, NSW, 2052, Australia., Selesniemi K; Paul F Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, Boston, MA, USA., Wong D; School of Biomedical Sciences, UNSW Sydney, Kensington, NSW, 2052, Australia., Madawala R; School of Biomedical Sciences, UNSW Sydney, Kensington, NSW, 2052, Australia., Marchante M; IVI Foundation, Valencia, Spain.; Department of Pediatrics, Obstetrics and Gynaecology, Faculty of Medicine, University of Valencia, Valencia, Spain., Goss DM; School of Biomedical Sciences, UNSW Sydney, Kensington, NSW, 2052, Australia., Li C; School of Biomedical Sciences, UNSW Sydney, Kensington, NSW, 2052, Australia., Araki T; Department of Peripheral Nervous System Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo, 187-8502, Japan., Livingston DJ; Metro International Biotech, Worcester, MA, USA., Turner N; School of Biomedical Sciences, UNSW Sydney, Kensington, NSW, 2052, Australia.; Victor Chang Cardiac Research Institute, Darlinghurst, NSW, 2010, Australia., Sinclair DA; Paul F Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, Boston, MA, USA., Walters KA; School of Clinical Medicine, UNSW Sydney, Kensington, NSW, 2052, Australia., Homer HA; School of Clinical Medicine, UNSW Sydney, Kensington, NSW, 2052, Australia.; Christopher Chen Oocyte Biology Laboratory, University of Queensland Centre for Clinical Research, Royal Brisbane & Women's Hospital, Herston, QLD, 4029, Australia., Gilchrist RB; School of Clinical Medicine, UNSW Sydney, Kensington, NSW, 2052, Australia., Wu LE; School of Biomedical Sciences, UNSW Sydney, Kensington, NSW, 2052, Australia. lindsay.wu@unsw.edu.au.
Jazyk:	angličtina
Zdroj:	EMBO molecular medicine [EMBO Mol Med] 2024 Oct; Vol. 16 (10), pp. 2583-2618. Date of Electronic Publication: 2024 Aug 21.
DOI:	10.1038/s44321-024-00119-w
Abstrakt:	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) + metabolome could protect ovarian function. We show that pharmacological or transgenic strategies to replenish the NAD + 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 + 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 + precursors could be a non-invasive strategy for maintaining ovarian function in cancer patients, with potential benefits in cancer therapy. (© 2024. The Author(s).)
Databáze:	MEDLINE
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