BNC1 deficiency induces mitochondrial dysfunction-triggered spermatogonia apoptosis through the CREB/SIRT1/FOXO3 pathway: the therapeutic potential of nicotinamide riboside and metformin†.
Level 5 - mechanism / opinion, no new human data
Animal and in vitro mechanistic laboratory study
PubMed 38079523 · doi:10.1093/biolre/ioad168
What was done
Researchers investigated the mechanism of spermatogenic failure caused by Basonuclin 1 (BNC1) deficiency using Bnc1 truncation mutant mice, Bnc1-knockdown spermatogonia cell models, and human testis biopsies from patients with nonobstructive azoospermia. They evaluated mitochondrial function, apoptosis, and CREB/SIRT1/FOXO3 pathway activity, and tested therapeutic rescue using oral dietary supplementation or cell treatment with nicotinamide riboside or metformin.
What was found
The abstract does not report specific numerical data, sample sizes, or effect sizes. Bnc1 truncation mutation induced spermatogonia apoptosis linked to mitochondrial dysfunction (lower mitochondrial membrane potential and elevated reactive oxygen species) via downregulation of CREB/SIRT1/FOXO3 signaling. Treatment with nicotinamide riboside or metformin restored CREB/SIRT1/FOXO3 signaling, mitigated mitochondrial dysfunction and apoptosis in vitro, and improved seminiferous tubule architecture, reduced testicular apoptosis, and enhanced fertility in mutant mice.
Why it matters
The findings identify a specific mitochondrial and signaling pathway linking BNC1 deficiency to spermatogenic failure. They point to potential preclinical therapeutic utility for metabolic activators like nicotinamide riboside and metformin in specific genetic causes of male infertility.
Limits
The abstract reports no quantitative values, sample sizes, dosage details, or statistical confidence intervals. The therapeutic rescue was demonstrated strictly in animal and in vitro models, leaving human clinical efficacy and safety unproven.
Cited by
- supports Nicotinamide riboside (NR) is involved in improving fertility, sperm health, and egg health by improving mitochondrial health.