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

Abstract

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 NADmetabolome 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 NADprecursor 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 NADprecursors could be a non-invasive strategy for maintaining ovarian function in cancer patients, with potential benefits in cancer therapy.