Oxidative stress and sperm function: A systematic review on evaluation and management

Sulagna Dutta, Ahmad Majzoub, Ashok Agarwal, Sulagna Dutta, Ahmad Majzoub, Ashok Agarwal

Abstract

Objective: To review and present the most distinct concepts on the association of reactive oxygen species (ROS) with male reproduction. Methods: The Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines were used to search PubMed, Medline, EMBASE, and the Cochrane electronic databases for studies investigating the role of oxidative stress (OS) on sperm function. Results: The literature search yielded 1857 studies, of which 1791 articles were excluded because of irrelevance of data, non-English language, non-human nature or because they were case reports or commentaries. All included studies were reviews (46), meta-analyses (one), original research studies (18) and guideline articles (one). The studies were published between 1984 and 2018. Under normal physiological conditions, ROS are vital for sperm maturation, hyperactivation, capacitation, acrosome reaction, as well as fertilisation. However, a number of endogenous and exogenous causes may induce supra-physiological levels of ROS resulting in lipid peroxidation, sperm DNA fragmentation and apoptosis, and consequently infertility. Several laboratory testing methods can be used in infertile men to diagnose OS. Treatment usually involves antioxidant supplementation and, when possible, elimination of the causative factor. Conclusion: OS is an important cause of male factor infertility. Its assessment provides essential information that can guide treatment strategies aimed at improving the male's reproductive potential. Abbreviations: bp: base-pair; CAT: catalase; LPO: lipid peroxidation; MDA: malondialdehyde; MiOXSYS: Male Infertility Oxidative System; mtDNA: mitochondrial DNA; NAD(PH): nicotinamide adenine dinucleotide (phosphate); NO: nitric oxide; 8-OHdG: 8-hydroxy-2'-deoxyguanosine; ORP: oxidation-reduction potential; OS: oxidative stress; PKA: protein kinase A; PLA2: phospholipase A2; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses; PUFA: poly-unsaturated fatty acid; ROS: reactive oxygen species; SOD: superoxide dismutase; TAC: total antioxidant capacity; TBA: thiobarbituric acid.

Keywords: Male infertility; oxidative stress; reactive oxygen species; sperm function.

Figures

Figure 1.
Figure 1.
Flow chart of study selection according to PRISMA checklist.
Figure 2.
Figure 2.
Generation of ROS in spermatozoa.
Figure 3.
Figure 3.
OS in male reproduction.

References

    1. Thompson A, Agarwal A, Du Plessis SS.. Physiological role of reactive oxygen species in sperm function: a review In: Parekattil SJ, Agarwal A, editors. Antioxidants in male infertility: a guide for clinicians and researchers. New York, USA: Springer Science and Business Media; 2013. p. 69–89.
    1. Agarwal A, Atikin RJ, Alvarez JG, eds. Studies on men’s health and fertility (oxidative stress in applied basic research and clinical practice). New York City, NY, USA: Humana Press; 2012.
    1. Halliwell B, Cross CE. Oxygen-derived species: their relation to human disease and environmental stress. Environ Health Perspect. 1994;102(Suppl. 10):5–12.
    1. Agarwal A, Saleh RA, Bedaiwy MA. Role of reactive oxygen species in the pathophysiology of human reproduction. Fertil Steril. 2003;79:829–843.
    1. Alvarez JG, Storey BT. Assessment of cell damage caused by spontaneous lipid peroxidation in rabbit spermatozoa. Biol Reprod. 1984;30:323–331.
    1. Agarwal A, Sharma R, Gupta S, et al eds. Oxidative stress in human reproduction: shedding light on a complicated phenomenon. New York City, NY, USA: Springer Publishing; 2017.
    1. Agarwal A, Sharma RK, Nallella KP, et al. Reactive oxygen species as an independent marker of male factor infertility. Fertil Steril. 2006;86:878–885.
    1. Agarwal A, Makker K, Sharma R. Clinical relevance of oxidative stress in male factor infertility: an update. Am J Reprod Immunol. 2008;59:2–11.
    1. Doshi SD, Sharma RK, Agarwal A. Oxidative stress in unexplained male infertility In: Schattman GL, Esteves SC, Agarwal A, editors. Unexplained infertility: pathophysiology, evaluation and treatment. New York City, NY: Springer-Verlag; 2015; 81–89.
    1. Agarwal A, Hamada A, Esteves SC. Insight into oxidative stress in varicocele-associated male infertility: part 1. Nat Rev Urol. 2012;9:678–690.
    1. Hamada A, Esteves SC, Agarwal A. Insight into oxidative stress in varicocele-associated male infertility: part 2. Nat Rev Urol. 2013;10:26–37.
    1. Potts JM, Pasqualotto FF. Seminal oxidative stress in patients with chronic prostatitis. Andrologia. 2003;35:304–308.
    1. Sabeti P, Pourmasumi S, Rahiminia T, et al. Etiologies of sperm oxidative stress. Int J Reprod Biomed (Yazd). 2016;14:231–240.
    1. Agarwal A, Tvrda E, Sharma R. Relationship amongst teratozoospermia, seminal oxidative stress and male infertility. Reprod Biol Endocrinol. 2014;12:45.
    1. Moher D, Liberati A, Tetzlaff J, et al.; PRISMA Group . Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151:264–269, W64.
    1. Henkel RR. Leukocytes and oxidative stress: dilemma for sperm function and male fertility. Asian J Androl. 2011;13:43–52.
    1. Chen SJ, Allam JP, Duan YG, et al. Influence of reactive oxygen species on human sperm functions and fertilizing capacity including therapeutical approaches. Arch Gynecol Obstet. 2013;288:191–199.
    1. Baker MA, Krutskikh A, Aitken RJ. Biochemical entities involved in reactive oxygen species generation by human spermatozoa. Protoplasma. 2003;221:145–151.
    1. Ford WC, Whittington K, Williams AC. Reactive oxygen species in human sperm suspensions: production by leukocytes and the generation of NADPH to protect sperm against their effects. Int J Androl. 1997;20(Suppl. 3):44–49.
    1. World Health Organization, Department of Reproductive Health and Research WHO laboratory manual for the examination and processing of human semen. Fifth Geneva: World Health Organization; 2010. p. 7–113
    1. Rengan AK, Agarwal A, van der Linde M, et al. An investigation of excess residual cytoplasm in human spermatozoa and its distinction from the cytoplasmic droplet. Reprod Biol Endocrinol. 2012;10:92.
    1. Agarwal A, Prabakaran S, Allamaneni SS. Relationship between oxidative stress, varicocele and infertility: a meta-analysis. Reprod Biomed Online. 2006;12:630–633.
    1. Makker K, Agarwal A, Sharma R. Oxidative stress & male infertility. Indian J Med Res. 2009;129:357–367.
    1. Cho CL, Esteves SC, Agarwal A. Novel insights into the pathophysiology of varicocele and its association with reactive oxygen species and sperm DNA fragmentation. Asian J Androl. 2016;18:186–193.
    1. Will MA, Swain J, Fode M, et al. The great debate: varicocele treatment and impact on fertility. Fertil Steril. 2011;95:841–852.
    1. Agarwal A, Deepinder F, Sharma RK, et al. Effect of cell phone usage on semen analysis in men attending infertility clinic: an observational study. Fertil Steril. 2008;89:124–128.
    1. Aitken RJ, Gibb Z, Baker MA, et al. Causes and consequences of oxidative stress in spermatozoa. Reprod Fertil Dev. 2016;28:1–10.
    1. Agarwal A, Virk G, Ong C, et al. Effect of oxidative stress on male reproduction. World J Mens Health. 2014;32:1–17.
    1. Bj H, Nixon B, Bv K, et al. The effects of radiofrequency electromagnetic radiation on sperm function. Reproduction. 2016;152:R263–R276.
    1. Sengupta P, Dutta S, Krajewska-Kulak E. The disappearing sperms: analysis of reports published between 1980 and 2015. Am J Mens Health. 2017;11:1279–1304.
    1. Saleh RA, Agarwal A, Sharma RK, et al. Effect of cigarette smoking on levels of seminal oxidative stress in infertile men: a prospective study. FertilSteril. 2002;78:491–499.
    1. Agarwal A, Prabakaran SA. Mechanism, measurement, and prevention of oxidative stress in male reproductive physiology. Indian J Exp Biol. 2005;43:963–974.
    1. Sengupta P. Current trends of male reproductive health disorders and the changing semen quality. Int J Prev Med. 2014;5:1–5.
    1. Aitken RJ, Kt J, Sa R. Reactive oxygen species and sperm function - in sickness and in health. J Androl. 2012;33:1096–1106.
    1. Sikka SC. Oxidative stress and role of antioxidants in normal and abnormal sperm function. Front Biosci. 1996;1:e78–e86.
    1. Du Plessis SS, Agarwal A, Halabi J, et al. Contemporary evidence on the physiological role of reactive oxygen species in human sperm function. J Assist Reprod Genet. 2015;32:509–520.
    1. Griveau JF, Le L. Reactive oxygen species and human spermatozoa: physiology and pathology. Int J Androl. 1997;20:61–69.
    1. de Lamirande E, Gagnon C. Impact of reactive oxygen species on spermatozoa: a balancing act between beneficial and detrimental effects. Hum Reprod. 1995;10(Suppl. 1):15–21.
    1. Fujii J, Tsunoda S. Redox regulation of fertilisation and the spermatogenic process. Asian J Androl. 2011;13:420–423.
    1. Suarez SS. Control of hyperactivation in sperm. Hum Reprod Update. 2008;14:647–657.
    1. Aitken RJ. Reactive oxygen species as mediators of sperm capacitation and pathological damage. Mol Reprod Dev. 2017;84:1039–1052.
    1. Aitken RJ, Ma B, Nixon B. Are sperm capacitation and apoptosis the opposite ends of a continuum driven by oxidative stress? Asian J Androl. 2015;17:633–639.
    1. Khosrowbeygi A, Zarghami N. Fatty acid composition of human spermatozoa and seminal plasma levels of oxidative stress biomarkers in subfertile males. Prostaglandins Leukot Essent Fatty Acids. 2007;77:117–121.
    1. Kothari S, Thompson A, Agarwal A, et al. Free radicals: their beneficial and detrimental effects on sperm function. Indian J Exp Biol. 2010;48:425–435.
    1. Aitken RJ. Free radicals, lipid peroxidation and sperm function. Reprod Fertil Dev. 1995;7:659–668.
    1. Opuwari CS, Rr H. An update on oxidative damage to spermatozoa and oocytes. Biomed Res Int. 2016;2016:9540142.
    1. Shen H, Ong C. Detection of oxidative DNA damage in human sperm and its association with sperm function and male infertility. Free Radic Biol Med. 2000;28:529–536.
    1. Tremellen K. Oxidative stress and male infertility – a clinical perspective. Hum Reprod Update. 2008;14:243–258.
    1. Aydemir B, Onaran I, Kiziler AR, et al. The influence of oxidative damage on viscosity of seminal fluid in infertile men. J Androl. 2008;29:41–46.
    1. Agarwal A, Majzoub A. Laboratory tests for oxidative stress. Indian J Urol. 2017;33:199–206.
    1. McCord JM. The evolution of free radicals and oxidative stress. Am J Med. 2000;108:652–659.
    1. Agarwal A, Roychoudhury S, Bjugstad KB, et al. Oxidation-reduction potential of semen: what is its role in the treatment of male infertility? Ther Adv Urol. 2016;8:302–318.
    1. Rael LT, Bar-Or R, Aumann RM, et al. Oxidation-reduction potential and paraoxonase-arylesterase activity in trauma patients. Biochem Biophys Res Commun. 2007;361:561–565.
    1. Rael LT, Bar-Or R, Mains CW, et al. Plasma oxidation-reduction potential and protein oxidation in traumatic brain injury. J Neurotrauma. 2009;26:1203–1211.
    1. Agarwal A, Sharma R, Roychoudhury S, et al. MiOXSYS: a novel method of measuring oxidation reduction potential in semen and seminal plasma. Fertil Steril. 2016;106:566–573.
    1. Agarwal A, Roychoudhury S, Sharma R, et al. Diagnostic application of oxidation-reduction potential assay for measurement of oxidative stress: clinical utility in male factor infertility. Reprod Biomed Online. 2017;34:48–57.
    1. Homa ST, Vessey W, Perez-Miranda A, et al. Reactive oxygen species (ROS) in human semen: determination of a reference range. J Assist Reprod Genet. 2015;32:757–764.
    1. Agarwal A, Sharma RK, Sharma R, et al. Characterizing semen parameters and their association with reactive oxygen species in infertile men. Reprod Biol Endocrinol. 2014;12:33.
    1. Badade G, More K, Narshetty G, et al. Human seminal oxidative stress: correlation with antioxidants and sperm quality parameters. Ann Bioll Res. 2011;2:351–359.
    1. Venkatesh S, Gupta NP, Kumar R, et al. Correlation of sperm morphology and oxidative stress in infertile men. Iran J Reprod Med. 2009;7:29–34.
    1. El-Taieb MA, Alib MA, Nadac EA. Oxidative stress and acrosomal morphology: A cause of infertility in patients with normal semen parameters. Middle East Fertil Soc J. 2015;20:79–85.
    1. El-Sakka AI. Routine assessment of sperm DNA fragmentation in clinical practice: commentary and perspective. Transl Androl Urol. 2017;6(Suppl. 4):S640–S643.
    1. Agarwal A, Majzoub A, Esteves SC, et al. Clinical utility of sperm DNA fragmentation testing: practice recommendations based on clinical scenarios. Transl Androl Urol. 2016;5:935–950.
    1. Iommiello VM, Albani E, Di Rosa A, et al. Ejaculate oxidative stress is related with sperm DNA fragmentation and round cells. Int J Endocrinol. 2015;2015:321901.
    1. Dorostghoal M, Kazeminejad SR, Shahbazian N, et al. Oxidative stress status and sperm DNA fragmentation in fertile and infertile men. Andrologia. 2017;49:e12762.
    1. Majzoub A, Arafa M, Mahdi M, et al. Oxidation-reduction potential and sperm DNA fragmentation, and their associations with sperm morphological anomalies amongst fertile and infertile men. Arab J Urol. 2018;16:87–95.
    1. Sengupta P. Recent trends in male reproductive health problems. Asian J Pharm Clin Res. 2014;7:1–5.
    1. Sengupta P, Dutta S. Metals In: Skinner MK, editor. Reference module in biomedical sciences: encyclopedia of reproduction. 2nd ed. San Diego, CA, USA: Elsevier Science Publishing Co. Inc; 2018, chapter 99. p. 579–587.
    1. Hammadeh ME, Filippos AA, Hamad MF. Reactive oxygen species and antioxidant in seminal plasma and their impact on male fertility. Int J Fertil Steril. 2009; 3: 87–110.
    1. McDowell LR, Wilkinson N, Madison R, et al. Vitamins and minerals functioning as antioxidants with supplementation considerations. Florida Ruminant Nutrition Symposium, 2007, Best Western Gateway Grand, Gainesville, FL, USA Available from: . Accessed August 2018.
    1. Sengupta P, Agarwal A, Pogrebetskaya M, et al. Role of Withaniasomnifera (Ashwagandha) in the management of male infertility. Reprod Biomed Online. 2018;36:311–326.
    1. Zini A, Al-Hathal N. Antioxidant therapy in male infertility: fact or fiction? Asian J Androl. 2011;13:374–381.
    1. Agarwal A, Majzoub A. Role of antioxidants in male infertility. BJUI Knowledge. 2016;1–9. DOI:10.18591/BJUIK.0510
    1. Agarwal A, Majzoub A. Role of antioxidants in assisted reproductive techniques. World J Mens Health. 2017;35:1–17.
    1. Magdi Y, Darwish E, Elbashir S, et al. Effect of modifiable lifestyle factors and antioxidant treatment on semen parameters of men with severe oligoasthenoteratozoospermia. Andrologia. 2017;49:e12694.
    1. Majzoub A, Agarwal A. Antioxidant therapy in idiopathic oligoasthenoteratozoospermia. Indian J Urol. 2017;33:207–214.
    1. Majzoub A, Agarwal A, Esteves SC. Antioxidants for elevated sperm DNA fragmentation: a mini review. Transl Androl Urol. 2017;6(Suppl. 4):S649–S653.
    1. Gharagozloo P, Aitken RJ. The role of sperm oxidative stress in male infertility and the significance of oral antioxidant therapy. Hum Reprod. 2011;26:1628–1640.
    1. Majzoub A, Agarwal A. Systematic review of antioxidant types and doses in male infertility: benefits on semen parameters, advanced sperm function, assisted reproduction and live-birth rate. Arab J Urol. 2018;16:113–124.
    1. Gomaa MD, Motawaa MA, Al-Nashar AM, et al. Impact of subinguinal varicocelectomy on serum testosterone to estradiol ratio in male patients with infertility. Urology. 2018;117:70–77.
    1. Mostafa T, Anis TH, El-Nashar A, et al. Varicocelectomy reduces reactive oxygen species levels and increases antioxidant activity of seminal plasma from infertile men with varicocele. Int J Androl. 2001;24:261–265.
    1. Chen SS, Huang WJ, Chang LS, et al. Attenuation of oxidative stress after varicocelectomy in subfertile patients with varicocele. J Urol. 2008;179:639–642.

Source: PubMed

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

3
S'abonner