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Peer-reviewedCC BY-NC-NDReproductive biomedicine online

Sperm Mitochondrial DNA Copy Number Exhibits Higher Longitudinal Consistency than Conventional Semen Parameters in a Clinical Cohort

  • Savni Sawant1,2
  • Emily Houle2
  • Elizabeth C. Cox2
  • Ricardo P. Bertolla2
  • Brian W. Whitcomb3
  • J. Richard Pilsner2,4
4 affiliations
  1. 1Department of Biochemistry, Microbiology, Immunology, Wayne State University School of Medicine, Detroit, Michigan, USA
  2. 2C.S. Mott Center for Human Growth and Development, Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan, USA
  3. 3School of Public Health and Health Sciences, Department of Biostatistics and Epidemiology, University of Massachusetts Amherst, Amherst, Massachusetts, USA
  4. 4Institute of Environmental Health Sciences, Wayne State University, Detroit, Michigan, USA
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Abstract

RESEARCH QUESTION: What is the temporal stability of sperm mitochondrial DNA copy number (mtDNAcn) relative to conventional semen parameters and sperm DNA integrity measures? DESIGN: Longitudinal observational study with repeated semen samples in which conventional semen parameters, sperm mitochondrial DNA copy number and sperm DNA integrity measures were assessed. Ninety-five men participating in the Folic Acid and Zinc Supplementation Trial (FAZST) who provided paired semen samples at baseline and at 2, 4 or 6 months. Temporal stability of sperm mtDNAcn, conventional semen parameters, high DNA stainability (HDS) and DNA fragmentation index (DFI) was assessed using intraclass correlation coefficients (ICCs). RESULTS: Sperm mtDNAcn and HDS had the highest temporal stability (ICCs >0.90), exceeding that of all conventional semen parameters and DFI (ICC range 0.37‒0.76). The temporal stability of sperm mtDNAcn was consistent across sample intervals, with no significant differences in ICCs between time points. Sperm mtDNAcn was inversely correlated with sperm concentration, total sperm count, motility and morphology, and positively correlated with DFI and HDS. CONCLUSION: Sperm mtDNAcn had greater temporal stability than conventional semen parameters, suggesting it may be less susceptible to short-term ejaculate variability and supporting further investigation of its potential utility as a biomarker of male reproductive health.

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Cite

BibTeXRIS
BibTeX
@article{sawant2026sperm,
  title = {{Sperm Mitochondrial DNA Copy Number Exhibits Higher Longitudinal Consistency than Conventional Semen Parameters in a Clinical Cohort}},
  author = {Savni Sawant and Emily Houle and Elizabeth C. Cox and Ricardo P. Bertolla and Brian W. Whitcomb and J. Richard Pilsner},
  journal = {Reproductive biomedicine online},
  year = {2026},
  month = sep,
  doi = {10.1016/j.rbmo.2026.105972},
  url = {https://doi.org/10.1016/j.rbmo.2026.105972},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Sperm Mitochondrial DNA Copy Number Exhibits Higher Longitudinal Consistency than Conventional Semen Parameters in a Clinical Cohort
AU  - Savni Sawant
AU  - Emily Houle
AU  - Elizabeth C. Cox
AU  - Ricardo P. Bertolla
AU  - Brian W. Whitcomb
AU  - J. Richard Pilsner
PY  - 2026
DA  - 2026/09/13
JO  - Reproductive biomedicine online
DO  - 10.1016/j.rbmo.2026.105972
UR  - https://doi.org/10.1016/j.rbmo.2026.105972
AB  - RESEARCH QUESTION: What is the temporal stability of sperm mitochondrial DNA copy number (mtDNAcn) relative to conventional semen parameters and sperm DNA integrity measures? DESIGN: Longitudinal observational study with repeated semen samples in which conventional semen parameters, sperm mitochondrial DNA copy number and sperm DNA integrity measures were assessed. Ninety-five men participating in the Folic Acid and Zinc Supplementation Trial (FAZST) who provided paired semen samples at baseline and at 2, 4 or 6 months. Temporal stability of sperm mtDNAcn, conventional semen parameters, high DNA stainability (HDS) and DNA fragmentation index (DFI) was assessed using intraclass correlation coefficients (ICCs). RESULTS: Sperm mtDNAcn and HDS had the highest temporal stability (ICCs >0.90), exceeding that of all conventional semen parameters and DFI (ICC range 0.37‒0.76). The temporal stability of sperm mtDNAcn was consistent across sample intervals, with no significant differences in ICCs between time points. Sperm mtDNAcn was inversely correlated with sperm concentration, total sperm count, motility and morphology, and positively correlated with DFI and HDS. CONCLUSION: Sperm mtDNAcn had greater temporal stability than conventional semen parameters, suggesting it may be less susceptible to short-term ejaculate variability and supporting further investigation of its potential utility as a biomarker of male reproductive health.
SN  - 1472-6483
SN  - 1472-6491
ER  -