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Updated: Jun 6, 2026

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High-Resolution Respirometry to Assess Mitochondrial Function in Human Spermatozoa
Published on: June 23, 2023
Aging Remodels Mitochondrial Architecture Across the Male Reproductive Axis
Suzanna Navarro1, Claude F Albritton2, Estevao Scudese3
1Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA.
Research Square
|June 5, 2026
Summary
Aging impacts male fertility by altering mitochondrial structure and function. This study reveals that the MICOS complex is crucial for sperm health, offering a potential therapeutic target for age-related reproductive decline.
Area of Science:
- Reproductive Biology
- Mitochondrial Biology
- Aging Research
Background:
- Male infertility is a growing concern, often linked to aging.
- The role of mitochondrial structural changes in age-related male infertility is not well understood.
Purpose of the Study:
- To investigate the influence of aging and MICOS complex dysfunction on male reproductive health.
- To identify molecular mechanisms underlying age-associated male infertility.
Main Methods:
- Analysis of a large cohort (121,064 males) from the 'All of Us' Research Program with age-stratified PheWAS, LabWAS, and GWAS.
- Microscopic examination (confocal, transmission electron microscopy, serial block face scanning electron microscopy) of human semen, Drosophila, and mouse testes.
- Investigated the impact of MICOS complex inhibition on sperm function and oxidative stress.
Main Results:
- Male infertility is associated with age-dependent clinical phenotypes, laboratory findings, and genetic loci linked to mitochondrial dysfunction.
- MICOS complex inhibition in human samples led to impaired sperm motility and increased oxidative stress.
- Aging caused significant mitochondrial remodeling in testes across Drosophila and mouse models, disrupting mitochondrial network organization.
Conclusions:
- Mitochondrial MICOS complex integrity is a key regulator of age-associated male infertility across species.
- Age-related decline in male reproductive health is linked to mitochondrial structural and functional alterations.
- The MICOS complex represents a potential therapeutic target for age-related male infertility.
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