{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T13:24:18Z","timestamp":1786973058371,"version":"build-2736575974"},"reference-count":96,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T00:00:00Z","timestamp":1786752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Spinal cord injury is strongly associated with male infertility, traditionally attributed to erectile and ejaculatory dysfunction. However, accumulating evidence demonstrates that infertility in this population extends beyond neurogenic impairment and involves profound biochemical and molecular alterations within the male reproductive system. The objective of this review is to synthesize current evidence on the role of oxidative stress, inflammation, and sperm DNA damage as central mechanisms driving impaired fertility in men with spinal cord injury. A comprehensive evaluation of clinical and experimental studies indicates that seminal plasma in affected individuals is characterized by elevated reactive oxygen species, reduced antioxidant capacity, and a pro-inflammatory cytokine profile, including increased levels of tumor necrosis factor alpha, interleukin 6, and interleukin 1 beta. These alterations are closely linked to leukocytospermia, mitochondrial dysfunction, and disruption of the blood\u2013testis barrier, creating a toxic microenvironment that compromises sperm function. As a consequence, spermatozoa exhibit reduced motility, impaired membrane integrity, and significantly increased DNA fragmentation and chromatin abnormalities. Elevated sperm DNA damage has been consistently associated with poor fertilization outcomes, reduced embryo quality, and increased risk of pregnancy loss in assisted reproductive settings. Importantly, these molecular defects persist even when sperm are retrieved using advanced techniques such as electroejaculation or surgical extraction, highlighting the need for targeted therapeutic strategies. Interventions aimed at reducing oxidative stress and modulating inflammation, including antioxidant supplementation and advanced sperm selection methods, show promise but remain insufficiently standardized. Future research should focus on the development of personalized approaches integrating molecular diagnostics and targeted therapies to improve reproductive outcomes in this population. Collectively, this review reframes spinal cord injury-related infertility as a complex inflammatory and oxidative disorder and underscores the importance of addressing sperm DNA integrity in clinical management.<\/jats:p>","DOI":"10.3390\/jcm15166312","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:01:26Z","timestamp":1786968086000},"page":"6312","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spinal Cord Injury-Related Male Infertility: Oxidative Stress, Inflammation, and Sperm DNA Damage"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9553-6803","authenticated-orcid":false,"given":"Athanasios","family":"Zikopoulos","sequence":"first","affiliation":[{"name":"University College London Hospital, London NW1 2BU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5287-4450","authenticated-orcid":false,"given":"Athanasios","family":"Zachariou","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Ioannina, 45500 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5119-9072","authenticated-orcid":false,"given":"Maria","family":"Filiponi","sequence":"additional","affiliation":[{"name":"Physical Medicine and Rehabilitation Centre Kentavros, 38222 Volos, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0207-3395","authenticated-orcid":false,"given":"Grigorios","family":"Daligkaros","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Ioannina, 45500 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandros","family":"Zikopoulos","sequence":"additional","affiliation":[{"name":"1st Department of Orthopedic Surgery, ATTIKO University General Hospital, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5614-8870","authenticated-orcid":false,"given":"Dimitrios","family":"Zachariou","sequence":"additional","affiliation":[{"name":"Physical Medicine and Rehabilitation Centre Kentavros, 38222 Volos, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasilios-Sebastian","family":"Paraschos","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Corewell Health Hospital, 4700 Schaefer Road, Suite 310, Dearborn, MI 48126, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Markoula","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Ioannina, 45110 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Zizzo, J., Gater, D.R., Hough, S., and Ibrahim, E. 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