Oxidative Stress and Genetic Factors in Male Infertility

Male infertility affects up to half of all couples experiencing conception difficulties and is often multifactorial. A substantial proportion of idiopathic cases arises from an imbalance between reactive oxygen species (ROS) and the body’s antioxidant defences, leading to oxidative stress that damages sperm membranes, DNA integrity and mitochondrial function. Genetic predispositions—including Y-chromosome microdeletions, single-gene mutations and functional polymorphisms in antioxidant and redox-regulating genes—modulate individual susceptibility to oxidative injury. Key antioxidant systems encompass superoxide dismutases, catalase and glutathione-based enzymes that neutralise ROS and maintain redox homeostasis. Emerging evidence highlights the interplay between environmental exposures that elevate ROS production and inherited variants that diminish antioxidant capacity, culminating in defective spermatogenesis, reduced sperm motility, abnormal morphology and increased DNA fragmentation. Understanding these mechanisms underpins the development of molecular diagnostics, targeted antioxidant therapies and personalised management strategies for men with infertility.

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Oxidative Stress and Genetic Factors in Male Infertility publication trend

The graph below shows the total number of articles in oxidative stress and genetic factors in male infertility across all publications each year (not limited to Nature Index journals).

Technical terms

Oxidative stress: A cellular state resulting from excess reactive oxygen species over antioxidant defences, causing macromolecular damage.

Reactive oxygen species (ROS): Chemically reactive molecules (e.g. superoxide, hydrogen peroxide) generated by metabolic processes or external factors.

Redox potential (sORP): A quantitative measure of the oxidation–reduction balance in a biological sample, reflecting oxidative stress status.

Polymorphism: Genetic variation at a single nucleotide or gene locus that may influence phenotype or disease risk.

Glutathione-S-transferase (GST): A family of enzymes that catalyse conjugation of glutathione to toxic electrophiles, protecting cells from oxidative damage.

Idiopathic infertility: Infertility with no identifiable cause after standard clinical and laboratory evaluation.

References

1. Decreased Klotho Expression Causes Accelerated Decline of Male Fecundity through Oxidative Injury in Murine Testis. Antioxidants (2023).
2. Enzymatic Antioxidant Defense and Polymorphic Changes in Male Infertility. Antioxidants (2022).
3. Association of GSTM1 Polymorphism and Redox Potential with Idiopathic Male Infertility. Journal of Clinical Medicine (2023).