Nicotinamide Riboside Restores Sperm Production and Male Fertility: Preclinical Findings

Synopsis

Male infertility is a widespread issue, and one cause may be mutations in the BNC1 gene, which is crucial for sperm development. This study found that mice with a Bnc1 mutation showed spermatogenic failure—a breakdown in sperm formation—due to mitochondrial dysfunction that increased oxidative stress and triggered cell death in spermatogonia (sperm precursor cells). Researchers discovered that this damage was linked to reduced activity in the CREB/SIRT1/FOXO3 pathway, which supports mitochondrial health and cell survival. Treating the mice with nicotinamide riboside (NR), a vitamin B3–derived NAD+ booster, or metformin restored mitochondrial function, activated the protective signaling pathway, and reduced testicular cell death. As a result, sperm production and fertility improved in the mutant mice. These findings suggest that oral NR or metformin supplementation could be a promising treatment for male infertility caused by genetic defects that disrupt mitochondrial function.

Journal

Biology of Reproduction