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Updated: May 12, 2026
High-Resolution Respirometry to Assess Mitochondrial Function in Human Spermatozoa
Published on: June 23, 2023
High-Resolution Imaging Reveals Mitochondrial Protein Imbalance in Sperm of Oligoasthenospermic Men
Pauline Teixeira1, Magalie Boguenet1,2, Florence Pascaretti-Grizon1
1MitoLab Team, MitoVasc Unit, CNRS UMR6015, INSERM U1083, Angers University, Angers, SFR ICAT, France.
Abstract:
Male infertility accounts for nearly half of global infertility cases and is often linked to poor sperm quality, such as oligospermia, asthenospermia, and teratospermia. Although the exact mechanisms remain unclear, mitochondria, which are critical for ATP production and reactive oxygen species generation during fertilization, are increasingly recognized as key players in male infertility but remain underexplored. ATP synthesis relies on respiratory chain complexes that establish a proton gradient across the inner mitochondrial membrane, powering the F0F1-ATP synthase. Proper stoichiometry of these complexes, encoded by both nuclear and mitochondrial DNA, is essential for efficient energy production. However, no previous studies have directly correlated mitochondrial protein expression with sperm quality. Due to the small size and helical structure of sperm mitochondria, imaging them is challenging, yet crucial for understanding sperm function. This study investigates the role of mitochondrial oxidative phosphorylation proteins in sperm quality using single-cell immunolabeling and high-resolution microscopy. It compares spermatozoa from oligoasthenospermic (OA) patients to normospermic controls. OA sperm show increased levels of mitochondrial genome encoded cytochrome c oxidase subunit 1 and significantly reduced F0F1-ATP synthase subunits. This imbalance may contribute to mitochondrial dysfunction and underscores the need for deeper exploration of the pathophysiological mechanisms involved, which could affect sperm function and fertility. These initial results suggest a potential pathway toward the identification of novel biomarkers of male infertility.
Insights
Mitochondrial protein imbalances, specifically increased cytochrome c oxidase and decreased ATP synthase, are linked to poor sperm quality in male infertility. This finding highlights potential new biomarkers for diagnosing male reproductive issues.
Area of Science:
- Reproductive Biology
- Mitochondrial Biology
- Biochemistry
Background:
- Male infertility affects nearly half of global infertility cases, often linked to poor sperm quality (oligospermia, asthenospermia, teratospermia).
- Mitochondria are crucial for sperm ATP production and fertilization, but their role in male infertility is underexplored.
- Efficient ATP synthesis depends on mitochondrial respiratory chain complexes and F0F1-ATP synthase, requiring proper stoichiometry.
Purpose of the Study:
- To investigate the correlation between mitochondrial oxidative phosphorylation protein expression and sperm quality in male infertility.
- To compare mitochondrial protein levels in spermatozoa from oligoasthenospermic (OA) patients versus normospermic controls.
Main Methods:
- Utilized single-cell immunolabeling and high-resolution microscopy to image sperm mitochondria.
- Analyzed the expression of mitochondrial genome-encoded and nuclear-encoded mitochondrial proteins.
- Compared protein expression profiles between OA patient spermatozoa and healthy controls.
Main Results:
- OA sperm exhibited significantly increased levels of mitochondrial genome-encoded cytochrome c oxidase subunit 1.
- OA sperm showed significantly reduced levels of F0F1-ATP synthase subunits.
- Identified an imbalance in mitochondrial protein stoichiometry in spermatozoa from infertile men.
Conclusions:
- The observed mitochondrial protein imbalance may contribute to mitochondrial dysfunction and impaired sperm function in male infertility.
- These findings suggest a potential link between specific mitochondrial proteins and male fertility.
- Further research into these pathophysiological mechanisms could lead to novel biomarkers for male infertility diagnosis.
