Mitochondrial Function and Oxidative Stress in Male Fertility
Summary
Mitochondria lie at the heart of sperm function, providing the ATP necessary for flagellar motility and the energetic demands of capacitation and acrosomal reaction. During normal respiration, mitochondria generate reactive oxygen species (ROS) as by-products of oxidative phosphorylation; at physiological levels these ROS serve as signalling molecules that regulate sperm maturation and fertilisation competence. However, when ROS production overwhelms endogenous antioxidant defences, oxidative stress ensues, leading to lipid peroxidation of the sperm plasma membrane, mitochondrial dysfunction, DNA fragmentation and activation of apoptotic pathways. The resulting decline in motility, viability and genetic integrity contributes substantially to male subfertility and infertility. Strategies to preserve mitochondrial performance and to restore redox balance—such as targeted antioxidant supplementation—have shown promise in improving semen parameters, reducing DNA damage and enhancing fertilisation outcomes. Growing evidence underscores the importance of maintaining mitochondrial membrane potential and optimizing the interplay between ROS generation and clearance, highlighting both mechanistic insights and potential therapeutic avenues in the management of male reproductive health.
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Mitochondrial Function and Oxidative Stress in Male Fertility publication trend
The graph below shows the total number of articles in mitochondrial function and oxidative stress in male fertility across all publications each year (not limited to Nature Index journals).
Technical terms
Reactive oxygen species (ROS): Highly reactive molecules derived from oxygen metabolism that act as signalling agents at low concentrations but cause oxidative damage when in excess.
Mitochondrial membrane potential (MMP): The electrochemical proton gradient across the inner mitochondrial membrane that drives ATP synthesis during oxidative phosphorylation.
Oxidative phosphorylation: The metabolic process in mitochondria by which electrons are transferred through respiratory complexes to generate ATP.
Lipid peroxidation: The oxidative degradation of polyunsaturated lipids in the sperm plasma membrane, leading to loss of fluidity and functional impairment.
Myo-inositol: A naturally occurring cyclic polyol that serves as an antioxidant and second messenger, supporting calcium homeostasis and mitochondrial efficiency in sperm cells.
References
- Oxidative Stress and Male Fertility: Role of Antioxidants and Inositols. Antioxidants (2021).
- Reactive oxygen species and sperm cells. Reproductive Biology and Endocrinology (2004).
- Respiratory Mitochondrial Efficiency and DNA Oxidation in Human Sperm after In Vitro Myo-Inositol Treatment. Journal of Clinical Medicine (2020).
- D-Chiro-Inositol Improves Sperm Mitochondrial Membrane Potential: In Vitro Evidence. Journal of Clinical Medicine (2020).
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