NMN Supplementation Rescues Fertility and Bone Strength in Chemotherapy-Treated Mice
Abstract
Background: Cancer survivors often face infertility as a result of ovarian toxicity from cytotoxic chemotherapy drugs, which trigger a cascade of events ultimately causing follicular reserve exhaustion and endocrine disruption. Apart from infertility, this can have severe consequences on women’s health with early-onset menopause and a decline in bone health. For girls with cancer, ovarian tissue cryopreservation (OTC) is the only option for fertility preservation. OTC + transplantation may provide future fertility potential, but it provides minimal/no protection from endocrine failure and osteoporosis.
Aim: To assess the effects of the nicotinamide adenine dinucleotide (NAD+) precursor nicotinamide mononucleotide (NMN) on ovarian function, fertility, and late-life bone health.
Method: 7-day old female mice were treated +/- cisplatin (2mg/kg). Two weeks later, +/- NMN was delivered in drinking water (2g/L) and sustained throughout life. A breeding trial was conducted at 6 weeks, and to assess late-life effects on bone structure, mice were maintained until euthanasia at 24 months of age.
Results: Cisplatin caused a dramatic decline in all fertility endpoints. NMN supplementation rescued breeding performance in cisplatin treated animals by 5-fold (p=0.015), as measured by the cumulative number of pups/female. Given the importance of ovarian function to estrogen release and the risk of osteoporosis, we sought to determine the impacts of these interventions on late-life bone health. Bones were subject to mechanical and structural analysis to assess differences in the onset of osteoporosis. In cisplatin treated animals, NMN rescued cortical bone thickness (femur diaphysis p0.0001, femur metaphysis p=0.0081, tibia p=0.0072), bone volume (femur p=0.0015, tibia p=0.0102), and bone density (femur p=0.0463) to control levels, and increased mechanical strength (tibia, p=0.0024).
Conclusion: Long-term NMN treatment delivered following chemotherapy protected against subsequent ovarian failure and infertility, and notably improved late-life bone health, possibly due to the prevention of premature ovarian failure.
Publisher's Note:
This article contains the abstract only.