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

**Authors:** Athanasios Zikopoulos, Panagiotis Christopoulos, Theodoros Kalampokas, Angeliki Gerede, Efthalia Moustakli, Ioannis Arkoulis, Spyridon Topis, Anastasios Potiris, Chrysi Christodoulaki, Ioannis Tsakiridis, Themistoklis Dagklis, Sofoklis Stavros

PMC · DOI: 10.3390/diagnostics16040527 · 2026-02-10

## TL;DR

This review explores how oxidative stress and inflammation contribute to male infertility and evaluates the potential of related biomarkers for improving diagnosis and treatment.

## Contribution

The paper critically assesses the clinical value and limitations of oxidative stress and inflammatory biomarkers in diagnosing male infertility.

## Key findings

- Oxidative stress and inflammation are linked to sperm damage and poor reproductive outcomes in infertile men.
- Biomarkers like MDA, 8-OHdG, and IL-6 show diagnostic potential but face challenges in standardization and clinical adoption.
- Biomarker-guided strategies may enhance personalized treatment approaches in male infertility.

## 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.

## Linked entities

- **Proteins:** IL6 (interleukin 6), IL8L1 (interleukin 8-like 1)
- **Chemicals:** malondialdehyde (PubChem CID 10964), 8-hydroxy-2′-deoxyguanosine (PubChem CID 135406132)
- **Diseases:** male infertility (MONDO:0005372)

## Full-text entities

- **Genes:** IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, G6PD (glucose-6-phosphate dehydrogenase) [NCBI Gene 2539] {aka CNSHA1, G6PD1}, MPO (myeloperoxidase) [NCBI Gene 4353], IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}
- **Diseases:** systemic disorders (MESH:D009422), cryptorchidism (MESH:D003456), prostatitis (MESH:D011472), infectious (MESH:D003141), Oligozoospermia (MESH:D009845), genitourinary infections (MESH:D014564), systemic (MESH:D015619), infected (MESH:D007239), immunological dysregulation (MESH:D007154), Infertility (MESH:D007246), teratozoospermia (MESH:D000072660), weight loss (MESH:D015431), OS (MESH:D000079225), RPL (OMIM:614389), impaired spermatogenesis (MESH:C536875), metabolic disorders (MESH:D008659), reproductive dysfunction (MESH:D060737), genetic defects (MESH:D030342), Male Infertility (MESH:D007248), varicocele (MESH:D014646), autoimmune (MESH:D001327), obesity (MESH:D009765), testicular torsion (MESH:D013086), male reproductive failure (MESH:D051437), diabetes mellitus (MESH:D003920), asthenozoospermia (MESH:D053627), orchitis (MESH:D009920), injury to (MESH:D014947), anatomical abnormalities (MESH:D020763), Inflammation (MESH:D007249), testicular dysfunction (MESH:D013733), metabolic syndrome (MESH:D024821), male reproductive dysfunction (MESH:D005832), mitochondrial dysfunction (MESH:D028361), epididymitis (MESH:D004823)
- **Chemicals:** alcohol (MESH:D000438), acetyl-L-carnitine (MESH:D000108), ROS (MESH:D017382), ATP (MESH:D000255), polyphenols (MESH:D059808), lipid (MESH:D008055), NADPH (MESH:D009249), selenium (MESH:D012643), fatty acids (MESH:D005227), MDA (MESH:D008315), Non-steroidal anti-inflammatory medicines (-), polyunsaturated fatty acids (MESH:D005231), L-carnitine (MESH:D002331), 8-OHdG (MESH:D000080242), testosterone (MESH:D013739), coenzyme Q10 (MESH:C024989), zinc (MESH:D015032)
- **Species:** Homo sapiens (human, species) [taxon 9606]

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Source: https://tomesphere.com/paper/PMC12939946