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Antioxidants and Male Infertility

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Male Infertility

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Abstract

Many causes of male infertility are unknown, and for this reason, numerous studies have been carried out, analyzing gene expression, epigenetics modifications, and mostly the role of reactive oxygen species (ROS) and antioxidants. It is well recognized that oxidative stress is a cause of male infertility, but the use of antioxidants as a treatment is still debated, and it is considered as a supportive therapy, rather than etiological or physiopathological, on the real effect of oral supplementation. Oxidative stress is determined when there is an imbalance between the production of ROS and the neutralizing activity of antioxidant system. It leads to a pathological and often irremediable cell damage. In particular spermatozoa are very susceptible to oxygen effects because their membranes are rich in polyunsaturated fatty acids that assure fluidity and flexibility; this one makes spermatozoa more vulnerable to lipid peroxidation.

The most important sources of ROS in semen are immature spermatozoa and leucocytes, and the protective antioxidant system in semen is divided into enzymatic factors, such as superoxide dismutase, catalase, glutathione peroxidase, and peroxiredoxins, and nonenzymatic factors. We focused our attention on the main natural antioxidants, the efficacy of which has been supported by clinical trials. In particular our group focused on the study of coenzyme Q10 and carnitine, but we will also review the other main antioxidants.

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References

  1. Agarwal A, Mulgund A, Hamada A, Chyatte MR. A unique view on male infertility around the globe. Reprod Biol Endocrinol. 2015 Apr 26;13:37.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Aitken RJ, Clarkson JS. Cellular basis of defective sperm function and its association with the genesis of reactive oxygen species by human spermatozoa. J Reprod Fertil. 1987;81:459–69.

    Article  CAS  PubMed  Google Scholar 

  3. Aitken RJ, Clarkson JS, Fishel S. Generation of reactive oxygen species, lipid peroxidation and human sperm function. Biol Reprod. 1989;40:183–97.

    Article  Google Scholar 

  4. Aitken RJ, Krausz C. Oxidative stress, DNA damage and the Y chromosome. Reproduction. 2001;122:497–506. Aitken RJ, Baker MA. Reactive oxygen species generation by human spermatozoa: a continuing enigma. Int J Androl. 2002;25:191–4.

    Article  CAS  PubMed  Google Scholar 

  5. Winston GW, Regoli F, Dugas AJ Jr, Fong JH, Blanchard KA. A rapid chromatographic assay for determining oxyradical scavenging capacity of antioxidants and biological fluids. Free Radic Biol Med. 1998;24:480–93.

    Article  CAS  PubMed  Google Scholar 

  6. Regoli F, Winston GW. Quantification of total antioxidant scavenging capacity (TOSC) of antioxidants for peroxynitrite, peroxyl radicals and hydroxyl radicals. Toxicol Appl Pharmacol. 1999;156:96–105.

    Article  CAS  PubMed  Google Scholar 

  7. Balercia G, Mantero F, Armeni T, Principato G, Regoli F. Oxyradical scavenging capacity toward different reactive species in seminal plasma and sperm cells. A possible influence on kinetic parameters. Clin Chem Lab Med. 2003;41:13–9.

    Article  CAS  PubMed  Google Scholar 

  8. Mancini A, Leone E, Festa R, Grande G, Di Donna V, De Marinis L, Pontecorvi A, Tacchino RM, Littarru GP, Silvestrini A, Meucci E. Evaluation of antioxidant systems (coenzyme Q10 and total antioxidant capacity) in morbid obesity before and after biliopancreatic diversion. Metab Clin Exp, USA. Oct 2008;57(10):1384–9.

    Article  CAS  Google Scholar 

  9. Rice-Evans C, Miller NJ. Total antioxidant status in plasma and body fluids. Methods Enzymol. 1994;234:279–93.

    Article  CAS  PubMed  Google Scholar 

  10. Mancini A, Leone E, Festa R, Grande G, Silvestrini A, de Marinis L, Pontecorvi A, Maira G, Littarru GP, Meucci E. Effects of testosterone on antioxidant systems in male secondary hypogonadism. J Androl, USA. 2008 Nov–Dec;29(6):622–9.

    Article  CAS  Google Scholar 

  11. Mancini A, Leone E, Silvestrini A, Festa R, Di Donna V, de Marinis L, Pontecorvi A, Littarru GP, Meucci E. Evaluation of antioxidant systems in pituitary-adrenal axis diseases. Pituitary, Springer-Verlag, Heidelberg-New York. 2010;13(2):138–45.

    CAS  Google Scholar 

  12. Mancini A, Di Segni C, Bruno C, Olivieri G, Guidi F, Silvestrini A, Meucci E, Orlando P, Silvestri S, Tiano L, Pontecorvi A. Oxidative stress in adult growth hormone deficiency: different plasma antioxidant patterns in comparison with metabolic syndrome. Endocrine. 2017 Nov 15; https://doi.org/10.1007/s12020-017-1468-1.

  13. Cutini M, Balercia G. Growth hormone and male reproduction, In: Mancini A, editor. Adult growth hormone deficiency: physiopathological and clinical aspects. Minerva Med. 1989;80(4):325–34.

    Google Scholar 

  14. Mancini A, Festa R, Silvestrini A, Nicolotti N, Di Donna V, La Torre G, Pontecorvi A, Meucci E. Hormonal regulation of total antioxidant capacity in seminal plasma. J Androl, USA. 2009 Sep–Oct;30(5):534–40.

    Article  CAS  Google Scholar 

  15. Agarwal A, Saleh R, Bedaiwy M. Role of reactive oxygen species in the pathophysiology of human reproduction. Fertil Steril. 2003;79:829–43. https://doi.org/10.1016/S0015-0282(02)04948-8.

    Article  PubMed  Google Scholar 

  16. Fraczek M, Kurpisz M. The redox system in human semen and peroxidative damage of spermatozoa. Postepy Hig Med Dosw. 2005;59:523–34.

    Google Scholar 

  17. Fisher HM, Aitken RJ. Comparative analysis of the ability of precursor germ cells and epididymal spermatozoa to generate reactive oxygen metabolites. J Exp Zool. 1997;277:390–400.

    Article  CAS  PubMed  Google Scholar 

  18. Henkel RR. Leukocytes and oxidative stress: dilemma for sperm function and male infertility. Asian J Androl. 2011;13:43–52. https://doi.org/10.1038/aja.2010.76.

    Article  CAS  PubMed  Google Scholar 

  19. O’Flaherty C. Peroxiredoxin 6: the protector of male fertility. Antioxidants (Basel). 2018 Nov 24;7(12):pii: E173. https://doi.org/10.3390/antiox7120173.

    Article  CAS  Google Scholar 

  20. Gaskin AJ, Chavarro JE. Diet and fertility: a review. Am J Obstet Gynecol. 2018;218(4):379–89.

    Article  Google Scholar 

  21. Yao DF, Mills JN. Male infertility: lifestyle factors and holistic, complementary and alternative therapies. Asian J Androl. 2016;18:410–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Pisarka MD. Fertility status and overall health. Semin Reprod Med. 2017;35(3):203–4.

    Article  Google Scholar 

  23. Mancini A, Martorana GE, Magini M, Festa R, Raimondo S, Silvestrini A, Nicolotti N, Mordente A, Mele MC, Miggiano GAD, Meucci E. Oxidative stress and metabolic syndrome: effects of a natural antioxidants enriched diet on insulin resistance. Clin Nutr ESPEN, Edinburgh (Scotland). 2015;10:e52–60.

    Article  Google Scholar 

  24. Festa R, Martorana GE, Magini M, Miggiano GAD, Mele C, Raimondo S, Pontecorvi A, Mancini A. Effetti di una dieta ricca di antiossidanti naturali sui livelli di testosterone in soggetti con insulino-resistenza. In: Foresta C, Lenzi A, Ferlin A, Garolla A, editors. Riproduzione e Sessualità. Padova: CLEUP; 2012 Febbraio. p. 337–9.

    Google Scholar 

  25. Giahi L, Mohammadmoradi S, Javidan A, Sadeghi MR. Nutritional modifications in male infertility: a systematic review covering 2 decades. Nutr Rev. 2015;74(2):118–30.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Bohmer T, Johansen L. Carnitine-binding related suppressed oxygen uptake by spermatozoa. Arch Androl. 1978;1:321–4.

    Article  PubMed  Google Scholar 

  27. Jeulin C, Lewin LM. Role of free l-carnitine and acetyl-l-carnitine in post-gonadal maturation of mammalian spermatozoa. Hum Reprod Update. 1996;2:87–102.

    Article  CAS  PubMed  Google Scholar 

  28. Balercia G, Regoli F, Armeni T, Koverech A, Mantero F, Boscaro M. Placebo-controlled double-blind randomized trial on the use of l-carnitine, l-acetylcarnitine, or combined l-carnitine and l-acetylcarnitine in men with idiopathic asthenozoospermia. Fertil Steril. 2005;84:662–71.

    Article  CAS  PubMed  Google Scholar 

  29. Costa M, Canale D, Filicori M, D’Iddio S, Lenzi A. L-carnitine in idiopathic asthenozoospermia: a multicenter study. Andrologia. 1994;26:155–9. Vicari E, Calogero AE. Effects of treatment with carnitines in infertile patients with prostato-vesiculo-epididymitis. Hum Reprod. 2001;16:2338–42.

    Article  CAS  PubMed  Google Scholar 

  30. Lenzi A, Lombardo F, Sgro P, Salacone P, Caponecchia L, Dondero F, et al. Use of carnitine therapy in selected cases of male factor infertility: a double blind cross-over trial. Fertil Steril. 2003;79:292–300.

    Article  PubMed  Google Scholar 

  31. Crane FL. Biochemical functions of coenzyme Q10. J Am Coll Nutr. 2001;20(6):591–8.

    Article  CAS  PubMed  Google Scholar 

  32. Sun IL, Sun EE, Crane FL. Comparison of growth stimulation of HeLa cells, HL-60 cells and mouse fibroblasts by coenzyme Q. Protoplasma. 1995;184:214–9.

    Article  CAS  Google Scholar 

  33. Stocker R, Bowry VW, Frei B. Ubiquinol-10 protects human low density lipoprotein more efficiently against lipid peroxidation than does alpha-tocopherol. Proc Natl Acad Sci U S A. 1991;88(5):1646–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Mazzilli F, Cerasaro M, Bisanti A, Rossi T, Dondero F. Seminal parameters and the swelling test in patients with sperm before and after treatment with ubiquinone (CoQ10). In: 2nd international symposium on reproductive medicine, Fiuggi, vol. 71. Rome: Acta Medica, Edizioni e Congressi; 1988.

    Google Scholar 

  35. Mazzilli F, Bisanti A, Rossi T, DeSantis L, Dondero F. Seminal and biological parameters in dysspermic patients with sperm hypomotility before and after treatment with ubiquinone (CoQ10). J Endocrinol Investig. 1990;13S(1):88.

    Google Scholar 

  36. Balercia G, Buldreghini E, Vignini A, Tiano L, Paggi F, Amoroso S, Ricciardo-Lamonica G, Boscaro M, Lenzi A, Littarru G. Coenzyme Q10 treatment in infertile men with idiopathic asthenozoospermia: a placebo-controlled, double-blind randomized trial. Fertil Steril. 2009;91:1785–92.

    Article  CAS  PubMed  Google Scholar 

  37. Balercia G, Mosca F, Mantero F, Boscaro M, Mancini A, Ricciardo-Lamonica G, Littarru G. Coenzyme Q(10) supplementation in infertile men with idiopathic asthenozoospermia: an open, uncontrolled pilot study. Fertil Steril. 2004;81:93–8.

    Article  CAS  PubMed  Google Scholar 

  38. World Health Organization (WHO). Laboratory manual for the examination of human semen and semen-cervical mucus interaction. 4th ed. Cambridge: Cambridge University; 1999.

    Google Scholar 

  39. Langsjoen P, Langsjoen A, Willis R, Folkers K. Treatment of hypertrophic cardiomyopathy with coenzyme Q10. Mol Asp Med. 1997;8:145–151s.

    Article  Google Scholar 

  40. Balercia G, Arnaldi G, Fazioli F, Serresi M, Alleva R, Mancini A, Mosca F, Lamonica GR, Mantero F, Littarru GP. Coenzyme Q10 levels in idiopathic and varicocele-associated asthenozoospermia. Andrologia. 2002;34:107–11.

    Article  CAS  PubMed  Google Scholar 

  41. Safarinejad MR. Efficacy of coenzyme Q10 on semen parameters, sperm function and reproductive hormones in infertile men. J Urol. 2009;182:237–48.

    Article  CAS  PubMed  Google Scholar 

  42. Tirabassi G, Vignini A, Tiano L, Buldreghini E, Brugè F, Silvestri S, Orlando P, D’Aniello A, Mazzanti L, Lenzi A, Balercia G. Protective effects of coenzyme Q10 and aspartic acid on oxidative stress and DNA damage in subjects affected by idiopathic asthenozoospermia. Endocrine. 2015 Jun;49(2):549–52.

    Article  CAS  PubMed  Google Scholar 

  43. Greco E, Iacobelli M, Rienzi L, Ubaldi F, Ferrero S, Tesarik J. Reduction of the incidence of sperm DNA fragmentation by oral antioxidant treatment. J Androl. 2005;26:349–53.

    Article  CAS  PubMed  Google Scholar 

  44. Moslemi MK, Tavanbakhsh S. Selenium-vitamin E supplementation in infertile men: effects on semen parameters and pregnancy rate. Int J Gen Med. 2011;4:99–104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Akmal M, Qadri JQ, Al-Waili NS, Thangal S, Haq A, Saloom KY. Improvement in human semen quality after oral supplementation of vitamin C. J Med Food. 2006;9:440–2.

    Article  CAS  PubMed  Google Scholar 

  46. Cyrus A, Kabir A, Goodarzi D, Moghimi M. The effect of adjuvant vitamin C after varicocele surgery on sperm quality and quantity in infertile men: a double blind placebo controlled clinical trial. Int Braz J Urol. 2015;41:230–8.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Kobori Y, Ota S, Sato R, Yagi H, Soh S, Arai G, et al. Antioxidant cosupplementation therapy with vitamin C, vitamin E, and coenzyme Q10 in patients with oligoasthenozoospermia. Arch Ital Urol Androl. 2014;86:1–4.

    Article  CAS  PubMed  Google Scholar 

  48. Favier AE. The role of zinc in reproduction: hormonal mechanisms. Biol Trace Elem Res. 1992;32:363–82.

    Article  CAS  PubMed  Google Scholar 

  49. Elgazar V, Razanov V, Stoltenberg M, Hershfinkel M, Huleihel M, Nitzan YB, et al. Zinc-regulating proteins, ZnT-1, and metallothionein I/II are present in different cell populations in the mouse testis. J Histochem Cytochem. 2005;53:905–12.

    Article  CAS  PubMed  Google Scholar 

  50. Zhao J, Dong X, Hu X, Long Z, Wang L, Liu Q, et al. Zinc levels in seminal plasma and their correlation with male infertility: a systematic review and meta-analysis. Sci Rep. 2016;6:22386.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Hunt CD, Johnson PE, Herbel J, Mullen LK. Effects of dietary zinc depletion on seminal volume and zinc loss, serum testosterone concentrations, and sperm morphology in young men. Am J Clin Nutr. 1992;56(1):148–57.

    Article  CAS  PubMed  Google Scholar 

  52. Carpino A, Siciliano L, Petroni M, De Stefano C, Aquila S, Ando S, et al. Low seminal zinc bound to high molecular weight proteins in asthenozoospermic patients: evidence of increased sperm zinc content in oligoasthenozoospermic patients. Hum Reprod. 1998;13(1):111–4.

    Article  CAS  PubMed  Google Scholar 

  53. Lin YC, Chang TC, Tseng YJ, Lin YL, Huang FJ, Kung FT, et al. Seminal plasma zinc levels and sperm motion characteristics in infertile samples. Chang Gung Med J. 2000;23(5):260–6.

    CAS  PubMed  Google Scholar 

  54. Eggert-Kruse W, Zwick EM, Batschulat K, Rohr G, Armbruster FP, Petzoldt D, et al. Are zinc levels in seminal plasma associated with seminal leukocytes and other determinants of semen quality? Fertil Steril. 2002;77(2):260–9.

    Article  PubMed  Google Scholar 

  55. Calogero AE, Gullo G, La Vignera S, Condorelli RA, Vaiarelli A. Myoinositol improves sperm parameters and serum reproductive hormones in patients with idiopathic infertility: a prospective double-blind randomized placebo-controlled study. Andrology. 2015;3:491–5.

    Article  CAS  PubMed  Google Scholar 

  56. Condorelli RA, La Vignera S, Mongioì LM, Vitale SG, Laganà AS, Cimino L, Calogero AE. Myo-inositol as a male fertility molecule: speed them up. Eur Rev Med Pharmacol Sci. 2017 Jun;21(2 Suppl):30–5.

    CAS  PubMed  Google Scholar 

  57. Liu DY, Clarke GN, Baker HW. Hyper-osmotic condition enhances protein tyrosine phosphorylation and zona pellucida binding capacity of human sperm. Hum Reprod. 2006;21:745–52.

    Article  CAS  PubMed  Google Scholar 

  58. Artini PG, Casarosa E, Carletti E, Monteleone P, Di Noia A, Di Berardino OM. In vitro effect of myo-inositol on sperm motility in normal and oligoasthenospermia patients undergoing in vitro fertilization. Gynecol Endocrinol. 2017;33:109–12.

    Article  CAS  PubMed  Google Scholar 

  59. Colone M, Marelli G, Unfer V. Bozz Uto G, Molinari a, Stringaro a. inositol activity in oligoasthenoteratospermia-an in vitro study. Eur Rev Med Pharmacol Sci. 2010;14:891–6.

    CAS  PubMed  Google Scholar 

  60. Condorelli RA, La Vignera S, Di Bari F, Unfer V, Calogero AE. Effects of myoinositol on sperm mitochondrial function in-vitro. Eur Rev Med Pharmacol Sci. 2011;15:129–34.

    CAS  PubMed  Google Scholar 

  61. Fox JT, Stover PJ. Folate-mediated one-carbon metabolism. Vitam Horm. 2008;79:1–44.

    Article  CAS  PubMed  Google Scholar 

  62. Tambi MIBM, Imran MK, Henkel RR. Standardised water-soluble extract of Eurycoma longifolia, Tongkat Ali, as testosterone booster for managing men with late-onset hypogonadism? Andrologia. 2012;44:226–30.

    Article  CAS  PubMed  Google Scholar 

  63. Solomon MC, Erasmus N, Henkel RR. In vivo effects of Eurycoma longifolia Jack (Tongkat Ali) extract on reproductive functions in the rat. Andrologia. 2014;46:339–48.

    Article  CAS  PubMed  Google Scholar 

  64. Peiris LDC, Dhanushka MAT, Jayathilake TAHDG. Evaluation of aqueous leaf extract of Cardiospermum halicacabum (L.) on fertility of male rats. Biomed Res Int. 2015;2015:175726.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Elahi RK, Asl S, Shahian F. Study on the effects of various doses of Tribulus terrestris extract on epididymal sperm morphology and count in rat. Global Vet. 2013;10:13–7.

    Google Scholar 

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Authors and Affiliations

  1. Division of Endocrinology, Department of Clinical and Molecular Sciences, Umberto I Hospital, Polytechnic University of Marche, Ancona, Italy

    Melissa Cutini & Giancarlo Balercia

  2. Operative Unit of Endocrinology, Fondazione Policlinico Universitario A.Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy

    Carmine Bruno & Antonio Mancini

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  1. Melissa Cutini
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  2. Carmine Bruno
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  4. Giancarlo Balercia
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Correspondence to Giancarlo Balercia .

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Editors and Affiliations

  1. PUR Clinic, University of Central Florida (UCF), Clermont, FL, USA

    Sijo J. Parekattil

  2. ANDROFERT and State University of Campinas (UNICAMP), Campinas, Brazil

    Sandro C. Esteves

  3. Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA

    Ashok Agarwal

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Cutini, M., Bruno, C., Mancini, A., Balercia, G. (2020). Antioxidants and Male Infertility. In: Parekattil, S., Esteves, S., Agarwal, A. (eds) Male Infertility. Springer, Cham. https://doi.org/10.1007/978-3-030-32300-4_43

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