The role of free radicals and antioxidants in male and female fertility disorders: review study

Document Type : Review Article

Authors

1 M.Sc. of Biology, School of Basic Sciences, Malayer University, Malayer, Iran.

2 M.Sc. of Anatomic Sciences, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran.

3 PhD, Department of Anatomic Sciences, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran. PhD, Department of Anatomic Sciences, Medical and Molecular Research Center, Faculty of Medicine, Arak University of Medical

Abstract

Introduction: Free radicals play a double role in the body based on their physiological level and can be beneficial or harmful. This review study was performed with aim to evaluate the cellular and molecular mechanisms of oxidative stress on spermatogenesis and oogenesis and the role of using antioxidant in improving fertility in men and women.
Methods: In this review study, the issues related to the role of free radicals and antioxidants on male and female fertility disorders were searched in the Persian and English databases including: Elsevier, Scopus, Irandoc, SID, Iran medex, Sciencedirect, Pubmed, GoogleScholar and Web of Science using the keywords of free radicals, male infertility, female infertility, and antioxidants without any time limitation. Finally, 63 studies entered the review study.
Results: The excessive production of free radicals in the male reproductive system causes damage to DNA, RNA, and sperm membranes, and ultimately disrupts spermatogenesis. It also causes disorders in the female genital tract including defect in oocyte development and maturation, follicular growth and function of corpus luteum.
Conclusion: According the results of previous studies, using antioxidants may remove the harmful effects of free radicals on male and female fertility.

Keywords

References

  1. Mosher WD, Pratt WF. Fecundity and infertility in the United States: incidence and trends. Fertility and sterility 1991; 56(2):192-3.
  2. De Lamirande E, Gagnon C. Impact of reactive oxygen species on spermatozoa: a balancing act between beneficial and detrimental effects. Human Reproduction 1995; 10(suppl_1):15-21.
  3. Potts JM, Pasqualotto FF. Seminal oxidative stress in patients with chronic prostatitis. Andrologia 2003; 35(5):304-8.
  4. Hendin BN, Kolettis PN, Sharma RK, Thomas JR AJ, Agarwal A. Varicocele is associated with elevated spermatozoal reactive oxygen species production and diminished seminal plasma antioxidant capacity. The Journal of urology 1999; 161(6):1831-4.
  5. Agarwal A, Aponte-Mellado A, Premkumar BJ, Shaman A, Gupta S. The effects of oxidative stress on female reproduction: a review. Reproductive biology and endocrinology 2012; 10(1):1-31.
  6. Barik G, Chaturvedula L, Bobby Z. Role of oxidative stress and antioxidants in male infertility: An interventional study. Journal of Human Reproductive Sciences 2019; 12(3):204.
  7. Vina J, Borras C, Abdelaziz KM, Garcia-Valles R, Gomez-Cabrera MC. The free radical theory of aging revisited: the cell signaling disruption theory of aging. Antioxidants & redox signaling 2013; 19(8):779-87.
  8. Powers SK, Jackson MJ. Exercise-induced oxidative stress: cellular mechanisms and impact on muscle force production. Physiological reviews 2008; 88(4):1243-76.
  9. Aldred S. Oxidative and nitrative changes seen in lipoproteins following exercise. Atherosclerosis 2007; 192(1):1-8.
  10. Du Plessis SS, Agarwal A, Halabi J, Tvrda E. Contemporary evidence on the physiological role of reactive oxygen species in human sperm function. Journal of assisted reproduction and genetics 2015; 32(4):509-20.
  11. Cory S, Adams JM. The Bcl2 family: regulators of the cellular life-or-death switch. Nature Reviews Cancer 2002; 2(9):647-56.
  12. Omar ME AS, Eman R Y, Hafez F H. The antioxidant status of the plasma in patients with breast cancer undergoing chemotherapy. Open Journal of Molecular and Integrative Physiology 2011; 2011.
  13. Klaunig JE, Kamendulis LM, Hocevar BA. Oxidative stress and oxidative damage in carcinogenesis. Toxicologic pathology 2010; 38(1):96-109.
  14. Buzadzic B, Vucetic M, Jankovic A, Stancic A, Korac A, Korac B, et al. New insights into male (in) fertility: the importance of NO. British journal of pharmacology 2015; 172(6):1455-67.
  15. John Aitken R, Clarkson JS, Fishel S. Generation of reactive oxygen species, lipid peroxidation, and human sperm function. Biology of reproduction 1989; 41(1):183-97.
  16. Zarghami N, Khosrowbeygi A. Evaluation of lipid peroxidation as an indirect measure of oxidative stress in seminal plasma. International Journal of Reproductive BioMedicine 2004; 2(1):34-0.
  17. Ollero M, Gil-Guzman E, Lopez MC, Sharma RK, Agarwal A, Larson K, et al. Characterization of subsets of human spermatozoa at different stages of maturation: implications in the diagnosis and treatment of male infertility. Human reproduction 2001; 16(9):1912-21.
  18. Trifunovic A, Hansson A, Wredenberg A, Rovio AT, Dufour E, Khvorostov I, et al. Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production. Proceedings of the National Academy of Sciences 2005; 102(50):17993-8.
  19. Fanaei H, Keshtgar S, Bahmanpour S, Ghannadi A, Kazeroni M. Beneficial effects of α-tocopherol against intracellular calcium overload in human sperm. Reproductive Sciences 2011; 18(10):978-82.
  20. Aziz N, Saleh RA, Sharma RK, Lewis-Jones I, Esfandiari N, Thomas Jr AJ, et al. Novel association between sperm reactive oxygen species production, sperm morphological defects, and the sperm deformity index. Fertility and sterility 2004; 81(2):349-54.
  21. Aitken RJ. The Amoroso Lecture The human spermatozoon–a cell in crisis?. Reproduction. 1999; 115(1):1-7.
  22. Ruder EH, Hartman TJ, Blumberg J, Goldman MB. Oxidative stress and antioxidants: exposure and impact on female fertility. Human reproduction update 2008; 14(4):345-57.
  23. Matteucci E, Giampietro O. Oxidative stress in families of type 1 diabetic patients. Diabetes care 2000; 23(8):1182-6.
  24. Sekhon L, Gupta S, Kim Y, Agarwal A. Female infertility and antioxidants. Current Women's Health Reviews 2010; 6(2):84-95.
  25. Fujii J, Iuchi Y, Okada F. Fundamental roles of reactive oxygen species and protective mechanisms in the female reproductive system. Reproductive biology and endocrinology 2005; 3(1):43.
  26. Sugino N, Takiguchi S, Kashida S, Karube A, Nakamura Y, Kato H. Superoxide dismutase expression in the human corpus luteum during the menstrual cycle and in early pregnancy. Molecular human reproduction 2000; 6(1):19-25.
  27. Du B, Takahashi K, Ishida GM, Nakahara K, Saito H, Kurachi H. Usefulness of intraovarian artery pulsatility and resistance indices measurement on the day of follicle aspiration for the assessment of oocyte quality. Fertility and sterility 2006; 85(2):366-70.
  28. Terada LS. Specificity in reactive oxidant signaling: think globally, act locally. The Journal of cell biology 2006; 174(5):615-23.
  29. Revelli A, Delle Piane L, Casano S, Molinari E, Massobrio M, Rinaudo P. Follicular fluid content and oocyte quality: from single biochemical markers to metabolomics. Reproductive biology and endocrinology 2009; 7(1):40.
  30. Miyamoto K, Sato EF, Kasahara E, Jikumaru M, Hiramoto K, Tabata H, et al. Effect of oxidative stress during repeated ovulation on the structure and functions of the ovary, oocytes, and their mitochondria. Free Radical Biology and Medicine 2010; 49(4):674-81.
  31. Dikmen A, Ergenoglu AM, Yeniel AO, Dilsiz OY, Ercan G, Yilmaz H. Evaluation of glycemic and oxidative/antioxidative status in the estradiol valerate-induced PCOS model of rats. European Journal of Obstetrics & Gynecology and Reproductive Biology 2012; 160(1):55-9.
  32. Victor VM, Rocha M, Bañuls C, Alvarez A, de Pablo C, Sanchez-Serrano M, et al. Induction of oxidative stress and human leukocyte/endothelial cell interactions in polycystic ovary syndrome patients with insulin resistance. The Journal of Clinical Endocrinology & Metabolism 2011; 96(10):3115-22.
  33. Polak G, Kozioł-Montewka M, Gogacz M, Błaszkowska I, Kotarski J. Total antioxidant status of peritoneal fluid in infertile women. European Journal of Obstetrics & Gynecology and Reproductive Biology 2001; 94(2):261-3.
  34. Webster RP, Roberts VH, Myatt L. Protein nitration in placenta–functional significance. Placenta 2008; 29(12):985-94.
  35. Mert I, Sargın Oruc A, Yuksel S, Cakar ES, Buyukkagnıcı U, Karaer A, et al. Role of oxidative stress in preeclampsia and intrauterine growth restriction. Journal of Obstetrics and Gynaecology Research 2012; 38(4):658-64.
  36. Kere M, Siriboon C, Lo NW, Nguyen NT, Ju JC. Ascorbic acid improves the developmental competence of porcine oocytes after parthenogenetic activation and somatic cell nuclear transplantation. Journal of Reproduction and Development 2012.
  37. Orazizadeh M, Khorsandi LS, Hashemitabar M. Toxic effects of dexamethasone on mouse testicular germ cells. Andrologia 2010; 42(4):247-53.
  38. Agarwal A, Sekhon LH. Oxidative stress and antioxidants for idiopathic oligoasthenoteratospermia: is it justified?. Indian journal of urology: IJU: journal of the Urological Society of India 2011; 27(1):74.
  39. Kessopoulou E, Powers HJ, Sharma KK, Pearson MJ, Russell JM, Cooke ID, et al. A double-blind randomized placebo cross-over controlled trial using the antioxidant vitamin E to treat reactive oxygen species associated male infertility. Fertility and Sterility 1995; 64(4):825-31.
  40. Showell MG, Mackenzie‐Proctor R, Brown J, Yazdani A, Stankiewicz MT, Hart RJ. Antioxidants for male subfertility. Cochrane Database of Systematic Reviews 2014(12).
  41. Aitken RJ, Smith TB, Jobling MS, Baker MA, De Iuliis GN. Oxidative stress and male reproductive health. Asian journal of andrology 2014; 16(1):31.
  42. Bansal AK, Bilaspuri GS. Impacts of oxidative stress and antioxidants on semen functions. Veterinary medicine international 2011; 2011.
  43. Lewis SE, Boyle PM, McKinney KA, Young IS, Thompson W. Total antioxidant capacity of seminal plasma is different in fertile and infertile men. Fertility and sterility 1995; 64(4):868-70.
  44. Makker K, Agarwal A, Sharma R. Oxidative stress & male infertility. Indian Journal of Medical Research 2009; 129(4):357.
  45. Eskenazi B, Kidd SA, Marks AR, Sloter E, Block G, Wyrobek AJ. Antioxidant intake is associated with semen quality in healthy men. Human reproduction 2005; 20(4):1006-12.
  46. Lewis SE, Sterling ES, Young IS, Thompson W. Comparison of individual antioxidants of sperm and seminal plasma in fertile and infertile men. Fertility and sterility 1997; 67(1):142-7.
  47. Zhou X, Liu F, Zhai S. Effect of L-carnitine and/or L-acetyl-carnitine in nutrition treatment for male infertility: a systematic review. Asia Pacific journal of clinical nutrition 2007; 16:383.
  48. Štajner D, Milić N, Čanadanović‐Brunet J, Kapor A, Štajner M, Popović BM. Exploring Allium species as a source of potential medicinal agents. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives 2006; 20(7):581-4.
  49. Liu J, Liu M, Ye X, Liu K, Huang J, Wang L, et al. Delay in oocyte aging in mice by the antioxidant N-acetyl-L-cysteine (NAC). Human reproduction 2012; 27(5):1411-20.
  50. Carbone MC, Tatone C, Monache SD, Marci R, Caserta D, Colonna R, et al. Antioxidant enzymatic defences in human follicular fluid: characterization and age‐dependent changes. MHR: Basic science of reproductive medicine 2003; 9(11):639-43.
  51. Briggs DA, Sharp DJ, Miller D, Gosden RG. Transferrin in the developing ovarian follicle: evidence for de-novo expression by granulosa cells. MHR: Basic science of reproductive medicine 1999; 5(12):1107-14.
  52. Kharb S. Vitamin E and C in preeclampsia. European Journal of Obstetrics & Gynecology and Reproductive Biology 2000; 93(1):37-9.
  53. Sharami SH, Bahadori MH, Fakor F, Mirblouk F, Kazemi S, Pourmarzi D, et al. Relationship between follicular fluid and serum levels of vitamin C and oocyte morphology and embryo quality in patients undergoing in vitro fertilization. IJWHR 2017; 5:41-6.
  54. Agarwal A, Said TM. Oxidative stress, DNA damage and apoptosis in male infertility: a clinical approach. BJU international 2005; 95(4):503-7.
  55. Asadi N, Bahmani M, Kheradmand A, Rafieian-Kopaei M. The impact of oxidative stress on testicular function and the role of antioxidants in improving it: a review. Journal of clinical and diagnostic research: JCDR 2017; 11(5):IE01.
  56. Agarwal A, Makker K, Sharma R. Clinical relevance of oxidative stress in male factor infertility: an update. American journal of reproductive immunology 2008; 59(1):2-11.
  57. Aslani BA, Ghobadi S. Studies on oxidants and antioxidants with a brief glance at their relevance to the immune system. Life sciences 2016; 146:163-73.
  58. Ross C, Morriss A, Khairy M, Khalaf Y, Braude P, Coomarasamy A, et al. A systematic review of the effect of oral antioxidants on male infertility. Reprod Biomed Online 2010; 20(6):711-23.
  59. Henkel R, Sandhu IS, Agarwal A. The excessive use of antioxidant therapy: A possible cause of male infertility? Andrologia 2019; 51(1):e13162.
  60. Bhardwaj JK, Mittal M, Saraf P, Kumari P. Pesticides induced oxidative stress and female infertility: a review. Toxin Reviews 2020; 39(1):1-13.
  61. Fujii J, Iuchi Y, Okada F. Fundamental roles of reactive oxygen species and protective mechanisms in the female reproductive system. Reproductive biology and endocrinology 2005; 3(1):1-10.
  62. Ghasemzadeh A, Farzadi L, Khaki A, Ahmadi SK. Effect of Allium cepa seeds ethanolic extract on experimental polycystic ovary syndrome (PCOS) apoptosis induced by estradiol-valerate. Life Science Journal 2013; 10(SUPPL. 4):170-5.
  63. Wang S, He G, Chen M, Zuo T, Xu W, Liu X. The Role of Antioxidant Enzymes in the Ovaries. Oxid Med Cell Longev 2017; 2017:4371714.

The Iranian Journal of Obstetrics, Gynecology and Infertility
Volume 24, Issue 2
April 2021
Pages 96-106

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