Sperm mitochondrial DNA copy number: a marker of male fertility and reproductive success.
Level 3 - non-randomized controlled study
Systematic review of observational cohort, epidemiologic, and experimental studies.
PubMed 42172631 · doi:10.1093/humupd/dmag013
What was done
The authors conducted a systematic literature search across PubMed, Web of Science, and Scopus through April 1, 2026, evaluating English-language human observational, clinical cohort, and experimental studies. The review analyzed sperm mitochondrial DNA copy number (mtDNAcn) in relation to semen quality, fertility, embryology outcomes, and underlying biological mechanisms (such as TFAM regulation and DNA methylation). A total of 21 studies met inclusion criteria.
What was found
The abstract reports directional associations without providing numeric data, effect sizes, or confidence intervals. Across 21 studies, elevated sperm mtDNAcn was consistently associated with lower sperm concentration, total count, motility, and normal morphology, as well as higher sperm DNA fragmentation and chromatin abnormalities. Elevated mtDNAcn was inconsistently linked to lower pregnancy likelihood and poorer embryo quality. Associations were also noted between sperm mtDNAcn and altered nuclear DNA methylation.
Why it matters
Sperm mtDNAcn reflects molecular processes during spermatogenesis and may serve as an adjunctive biomarker to complement traditional semen analysis in male reproductive assessment.
Limits
The abstract provides no quantitative effect sizes or pooled statistical metrics. Associations with couple-level reproductive outcomes remain inconsistent across included studies. Key methodological issues include a lack of standardized measurement protocols, variability across laboratory platforms, risk of somatic cell contamination, and undefined clinical cutoff thresholds.
Cited by
- supports Compelling scientific data links sperm mitochondrial DNA content per sperm to infertility.