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International Journal of Current Research in Physiology and Pharmacology
Review Articles
Submitted: 2024-10-24
Published: 2024-12-17

OXIDATIVE STRESS AND MALE INFERTILITY: MECHANISMS, BIOMARKERS, AND THERAPEUTIC IMPLICATIONS: A COMPREHENSIVE REVIEW

Dr Vithalrao Vikhe Patil Foundation’s Medical College, Ahilyanagar, Maharashtra
KIMS, Narketpally, Telangana
Oxidative stress; Male infertility; Reactive oxygen species; Sperm DNA fragmentation; Antioxidants; Seminal plasma; Spermatogenesis

Abstract

Male infertility accounts for approximately 40–50% of all infertility cases worldwide, with oxidative stress (OS) identified as a pivotal etiological contributor in up to 80% of infertile men. This review examines the molecular underpinnings of OS-mediated spermatotoxicity, its clinical manifestations, and emerging diagnostic and therapeutic strategies. A systematic narrative review was conducted utilizing peer-reviewed literature sourced from PubMed, Scopus,  Web of Science, and Google Scholar databases, encompassing publications from 1995 to 2024. Studies addressing reactive oxygen species (ROS) biology, spermatozoa redox physiology, antioxidant defense mechanisms, and clinical interventions were critically appraised and synthesized. Compelling evidence implicates elevated seminal ROS—primarily superoxide anion (O₂•⁻), hydrogen peroxide (H₂O₂), and hydroxyl radical (•OH)—in the pathogenesis of sperm DNA fragmentation, lipid peroxidation of the plasma membrane, and impaired mitochondrial membrane potential. These insults collectively compromise sperm motility, morphology, and fertilization competence. Seminal antioxidant capacity, as measured by total antioxidant capacity (TAC) and specific enzymatic activity (superoxide dismutase, catalase, glutathione peroxidase), is significantly attenuated in infertile cohorts. Oxidative stress represents a central, mechanistically validated axis of male reproductive dysfunction. Its reliable quantification and targeted pharmacological mitigation offer viable clinical avenues for improving assistedreproductive technology (ART) outcomes and natural fertility. Further large-scale randomized trials are warranted to standardize antioxidant supplementation protocols.

References

  1. World Health Organization. Infertility prevalence estimates 1990–2021. Geneva: World Health Organization; 2023. Available from: https://iris.who.int/server/api/core/bitstreams/a22ced65-46b1-4482-bf85-058719fec649/content
  2. Agarwal A, Baskaran S, Parekh N, Cho CL, Henkel R, Vij S, et al. Male infertility. Lancet. 2021;397(10271):319-333.
  3. Bisht S, Faiq M, Tolahunase M, Dada R. Oxidative stress and male infertility. Nat Rev Urol. 2017;14(8):470-485.
  4. Agarwal A, Virk G, Ong C, du Plessis SS. Effect of oxidative stress on male reproduction. World J Mens Health. 2014;32(1):1-17.
  5. Aitken RJ, Curry BJ. Redox regulation of human sperm function: from the physiological control of sperm capacitation to the etiology ofinfertility and DNA damage in the germ line. Antioxid Redox Signal. 2011;14(3):367-381.
  6. Sangishetti VP, Ghongane B, Nayak B. Role of oxidative stress and vitamin C, E on male fertility: mini review. Int J Biomed Allied HealthRes. 2017;1(1):13-21.6
  7. Halliwell B, Gutteridge JMC. Free radicals in biology and medicine. 5th ed. Oxford: Oxford University Press; 2015.
  8. Ochsendorf FR. Infections in the male genital tract and reactive oxygen species. Hum Reprod Update. 1999;5(5):399-420.
  9. Durairajanayagam D, Agarwal A, Ong C. Causes, effects and molecular mechanisms of testicular heat stress. Reprod Biomed Online.2015;30(1):14-27.
  10. Agarwal A, Roychoudhury S, Bjugstad KB, Cho CL. Oxidation-reduction potential of semen: what is its role in the treatment of male in‐fertility? Ther Adv Urol. 2016;8(5):302-316.
  11. O'Flaherty C, de Lamirande E, Gagnon C. Positive role of reactive oxygen species in mammalian sperm capacitation: triggering and mod‐ulation of phosphorylation events. Free Radic Biol Med. 2006;41(4):528-540.
  12. Roqueta-Rivera M, Stroud CK, Haas JT, Burgess SC, Ostrowski J, Nguyen CM, et al. Docosahexaenoic acid supplementation fully re‐stores fertility and spermatogenesis in male delta-6 desaturase-null mice. J Lipid Res. 2010;51(2):360-367.
  13. Mahfouz RZ, du Plessis SS, Aziz N, Sharma R, Sabanegh E, Agarwal A. Sperm viability, motility, and total antioxidant capacity in humansemen samples: impact of abstinence period. Fertil Steril. 2010;94(5):1572-1577.
  14. Sangishetti VP, Nandal DH, Nayak BB, Ghongane BB, Shinde BB, Kunkulol RR. Effect of stress on histopathology of male reproductivesystem in rats. Int J Curr Res Physiol Pharmacol. 2017;1(1):13-18.
  15. Shen HM, Ong CN. Detection of oxidative DNA damage in human sperm and its association with sperm function and male infertility. FreeRadic Biol Med. 2000;28(4):529-536.
  16. Zini A, Boman JM, Belzile E, Ciampi A. Sperm DNA damage is associated with an increased risk of pregnancy loss after IVF and ICSI:systematic review and meta-analysis. Hum Reprod. 2008;23(12):2663-2668.
  17. Gosálvez J, Fernández JL, Gosálvez A, Johnston SD, Tejón JL. Application of the sperm chromatin dispersion test to detect sperm DNAfragmentation in the context of sperm biology. J Androl. 2006;27(5):711-719.
  18. Koppers AJ, De Iuliis GN, Finnie JM, McLaughlin EA, Aitken RJ. Significance of mitochondrial reactive oxygen species in the generationof oxidative stress in spermatozoa. J Clin Endocrinol Metab. 2008;93(8):3199-3207.
  19. Bertolla RP, Cedenho AP, Hassun Filho PA, Lima SB, Ortiz V, Srougi M. Sperm nuclear DNA fragmentation in adolescents with varico‐cele. Fertil Steril. 2007;87(3):625-628.
  20. Iuchi Y, Okada F, Tsunoda S, Iuchi A, Ohtsuka Y, Ochiai A, et al. Peroxiredoxin 4 knockout results in elevated spermatogenic cell deathvia oxidative stress hazards in the testis. J Clin Invest. 2009;119(1):149-161.
  21. Sangishetti VP, Ghongane BB, Chourishi A, Vakade K, Kunkulol RR. Role of antioxidants in male reproduction: review. Int J Curr ResPhysiol Pharmacol. 2018;2(4):1-8.
  22. Lewis SE, Sterling ES, Young IS, Thompson W. Comparison of individual antioxidants of sperm and seminal plasma in fertile and infertilemen. Fertil Steril. 1997;67(1):142-147.
  23. Agarwal A, Parekh N, Panner Selvam MK, Henkel R, Shah R, Homa ST, et al. Male oxidative stress infertility (MOSI): proposed termino‐logy and clinical practice guidelines for management of idiopathic male infertility. World J Mens Health. 2019;37(3):296-312.
  24. Agarwal A, Arafa M, Chandrakumar R, Majzoub A, AlSaid S, Elbardisi H. A multicenter study to evaluate oxidative stress by oxidation-reduction potential, a reliable and reproducible method. Andrology. 2017;5(5):939-945.
  25. Cocuzza M, Cocuzza MA, Bragais FMP, Agarwal A. The role of varicocele repair in the new era of assisted reproductive technology. Clin‐ics (Sao Paulo). 2008;63(3):395-404.
  26. Agbaje IM, Rogers DA, McVicar CM, McClure N, Atkinson AB, Mallidis C, et al. Insulin dependant diabetes mellitus: implications formale reproductive function. Hum Reprod. 2007;22(7):1871-1877.
  27. Sangshetty VP, Prajapati K, Moharir G, Ojeh N, Sinha S, Kumar S, et al. The protective effect of Oxitard on sperm function and antioxid‐ant status in rats exposed to swimming stress. Cureus. 2023;15(6):e40381.
  28. Eskiocak S, Gozen AS, Taskiran A, Kilic AS, Eskiocak M, Gulen S. Effect of psychological stress on the L-arginine-nitric oxide pathwayand semen quality. Braz J Med Biol Res. 2005;38(9):1385-1392.
  29. Sharma R, Harlev A, Agarwal A, Esteves SC. Cigarette smoking and semen quality: a new meta-analysis examining the effect of the 2010World Health Organization laboratory methods for the examination of human semen. Eur Urol. 2016;70(4):635-645.
  30. Barratt CL, Björndahl L, De Jonge CJ, Lamb DJ, Osorio Martini F, McLachlan R, et al. The diagnosis of male infertility: an analysis of theevidence to support the development of global WHO guidance—challenges and future research opportunities. Hum Reprod Update.2017;23(6):660-680.
  31. Showell MG, Mackenzie-Proctor R, Brown J, Hart RJ. Antioxidants for male subfertility. Cochrane Database Syst Rev.2020;3(3):CD007411.31
  32. Lafuente R, González-Comadrán M, Solà I, López G, Brassesco M, Carreras R, et al. Coenzyme Q10 and male infertility: a meta-analysis.J Assist Reprod Genet. 2013;30(9):1147-1156.
  33. Sangishetti VP, Ghongane BB, Nayak BB. Effect of immobilization stress on organ indices, sperm quality, and testosterone level in rats:role of N-acetyl cysteine. J Chem Pharm Res. 2016;8(5):845-851.
  34. Sharma R, Agarwal A, Mohanty G, du Plessis SS, Gopalan B, Willard B, et al. Functional proteomic analysis of seminal plasma proteinsin men with various semen parameters. Reprod Biol Endocrinol. 2013;11(1):1-16.
  35. Aitken RJ, Gibb Z, Baker MA, Drevet J, Gharagozloo P. Causes and consequences of oxidative stress in spermatozoa. Reprod Fertil Dev.2016;28(2):1-10

How to Cite

Vakade, K. P., & Thandu, S. K. G. (2024). OXIDATIVE STRESS AND MALE INFERTILITY: MECHANISMS, BIOMARKERS, AND THERAPEUTIC IMPLICATIONS: A COMPREHENSIVE REVIEW. International Journal of Current Research in Physiology and Pharmacology, 8(4). Retrieved from https://ijcrpp.com/index.php/ijcrpp/article/view/94