Oxidative Stress and Inflammatory Biomarkers in Male Infertility: A Narrative Review of Diagnostic Value and Clinical Integration

Conventional semen analysis frequently fails to identify the underlying pathophysiology of male infertility, which is a complicated clinical disease, especially in cases of idiopathic infertility. A growing body of research indicates that inflammation and oxidative stress (OS) are important and related factors in male reproductive failure. Excessive reactive oxygen species (ROS) promote lipid peroxidation, protein oxidation, mitochondrial dysfunction, and sperm DNA fragmentation, thereby compromising motility, morphology, and fertilizing capacity. Concurrently, pro-inflammatory mediators like interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-α) are frequently found in the seminal plasma of infertile men and are linked to poor semen parameters and testicular dysfunction. It is crucial that oxidative and inflammatory pathways work together to create a self-sustaining pathophysiological cycle that exacerbates sperm damage and destabilizes the reproductive milieu. The diagnostic significance, clinical suitability, and limitations of oxidative stress and inflammation biomarkers, such as malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG), total antioxidant capacity (TAC), and specific inflammatory markers, are critically assessed in this comprehensive review. The lack of established diagnostic thresholds, methodological variation, and translational issues that still restrict their widespread clinical implementation are highlighted in particular. Additionally, the potential contribution of biomarker-guided approaches to focused therapy decisions and individualized patient management is explored. This study examines how oxidative and inflammatory markers may complement conventional male infertility assessments by supporting more precise, mechanism-based approaches in reproductive medicine, while addressing diagnostic readiness and translational limitations.

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Journal
Diagnostics
Published
2026-02-10
DOI
https://doi.org/10.3390/diagnostics16040527
Primary Topic
Sperm and Testicular Function
Type
article
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article

Oxidative Stress and Inflammatory Biomarkers in Male Infertility: A Narrative Review of Diagnostic Value and Clinical Integration

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Oxidative Stress and Inflammatory Biomarkers in Male Infertility: A Narrative Review of Diagnostic Value and Clinical Integration

Efthalia Moustakli, Angeliki Gerede, Spyridon Topis, Chrysi Christodoulaki, Ioannis Arkoulis, Anastasios Potiris, Ioannis Tsakiridis, Panagiotis Christopoulos, Sofoklis Stavros, Athanasios Zikopoulos, Theodoros Kalampokas
article en

Abstract

Conventional semen analysis frequently fails to identify the underlying pathophysiology of male infertility, which is a complicated clinical disease, especially in cases of idiopathic infertility. A growing body of research indicates that inflammation and oxidative stress (OS) are important and related factors in male reproductive failure. Excessive reactive oxygen species (ROS) promote lipid peroxidation, protein oxidation, mitochondrial dysfunction, and sperm DNA fragmentation, thereby compromising motility, morphology, and fertilizing capacity. Concurrently, pro-inflammatory mediators like interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-α) are frequently found in the seminal plasma of infertile men and are linked to poor semen parameters and testicular dysfunction. It is crucial that oxidative and inflammatory pathways work together to create a self-sustaining pathophysiological cycle that exacerbates sperm damage and destabilizes the reproductive milieu. The diagnostic significance, clinical suitability, and limitations of oxidative stress and inflammation biomarkers, such as malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG), total antioxidant capacity (TAC), and specific inflammatory markers, are critically assessed in this comprehensive review. The lack of established diagnostic thresholds, methodological variation, and translational issues that still restrict their widespread clinical implementation are highlighted in particular. Additionally, the potential contribution of biomarker-guided approaches to focused therapy decisions and individualized patient management is explored. This study examines how oxidative and inflammatory markers may complement conventional male infertility assessments by supporting more precise, mechanism-based approaches in reproductive medicine, while addressing diagnostic readiness and translational limitations.

DiagnosticsVol. 16(4)
Democritus University of Thrace (GR), University of Ioannina (GR), National and Kapodistrian University of Athens (GR), Aristotle University of Thessaloniki (GR), Alexandra Hospital (GR), Aretaeio Hospital (GR), Chania General Hospital ”St. George” (GR), Torbay and South Devon NHS Foundation Trust (GB)
Openalex Percentile: Top 62%
Sperm and Testicular Function
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