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.

中文翻译：

---

通过促进 NAD（P）+ 代谢组，在化疗期间保护生育能力。


化疗引起的卵巢衰竭和不孕症是育龄或年轻女性癌症患者的重要问题，迫切需要非侵入性药物方法来维持卵巢功能。鉴于还原烟酰胺腺嘌呤二核苷酸磷酸 （NADPH） 作为药物解毒的重要辅助因子的作用，我们试图测试增强 NAD（P）+ 代谢组是否可以保护卵巢功能。我们表明，通过卵母细胞产量、卵泡健康和功能育种试验来衡量，补充 NAD + 代谢组的药物或转基因策略可改善化疗诱导的小鼠雌性不育。重要的是，用 NAD+ 前体烟酰胺单核苷酸 （NMN） 治疗三阴性乳腺癌小鼠模型可减少肿瘤生长，并且不会损害化疗药物在体内或多种癌细胞系中的疗效。总体而言，这些发现提出了 NAD+ 前体可能成为维持癌症患者卵巢功能的非侵入性策略的可能性，在癌症治疗中具有潜在益处。