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Oxidative stress and male infertility: current knowledge of pathophysiology and role of antioxidant therapy in disease management

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Abstract

Infertility is a global health problem involving about 15% of couples. Approximately half of the infertility cases are related to male factors. The oxidative stress, which refers to an imbalance in levels of reactive oxygen species (ROS) and antioxidants, is one of the main causes of infertility in men. A small amount of ROS is necessary for the physiological function of sperm including the capacitation, hyperactivation and acrosomal reaction. However, high levels of ROS can cause infertility through not only by lipid peroxidation or DNA damage but inactivation of enzymes and oxidation of proteins in spermatozoa. Oxidative stress (OS) is mainly caused by factors associated with lifestyle. Besides, immature spermatozoa, inflammatory factors, genetic mutations and altering levels of sex hormones are other main source of ROS. Since OS occurs due to the lack of antioxidants and its side effects in semen, lifestyle changes and antioxidant regimens can be helpful therapeutic approaches to overcome this problem. The present study aimed to describe physiological ROS production, roles of genetic and epigenetic factors on the OS and male infertility with various mechanisms such as lipid peroxidation, DNA damage, and disorder of male hormone profile, inflammation, and varicocele. Finally, the roles of oral antioxidants and herbs were explained in coping with OS in male infertility.

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Abbreviations

·OH:

Hydroxyl

·ROO:

Proxyl

4-HNE:

4-Hydroxynonenal

8-OHdG:

8-Hydroxy-2-deoxyguanosine

ABP:

Androgen-binding protein

ARE:

Antioxidant responsive element

ARTs:

Assisted reproductive techniques

ATP:

Adenosine triphosphate

BER:

Base excision repair

cAMP:

Cyclic adenosine monophosphate

CAT:

Catalase

CK:

Creatine kinase

CYP2E:

Cytochrome P450 enzymes

ETC:

Electron transport chain

G6PD:

Glucose-6-phosphate dehydrogenase

GnRH:

Gonadotropin releasing hormone

GPx:

Glutathione peroxidase

GRX:

Glutaredoxin

GSH:

Glutathione

GST:

Glutathione s-transferase

H2O2 :

Hydrogen peroxide

HPA:

Hypothalamic–pituitary–adrenal

HPG:

Hypothalamic–pituitary–gonadal

HPT:

Hypothalamo–pituitary–thyroid

IL:

Interleukin

LOOHs:

Lipid hydroperoxides

MDA:

Malondialdehyde

miRNAs:

Micro-ribonucleic acids

MPO:

Myeloperoxidase

NAC:

N-Acetylcysteine

NADPH:

Adenine dinucleotide phosphate

NO:

Nitrogen oxide

NOS:

Nitric oxide synthase

NRF2:

Nuclear factor erythroid 2-related factor 2

O ·−2 :

Superoxide anion

ONOO-:

Peroxynitrite

OS:

Oxidative stress

P-Tyr:

Phosphotyrosine

PGE2:

Prostaglandin E2

PKA:

Protein kinase A

NER:

Nucleotide excision repair

PMN:

Polymorphonuclear

P-PKA:

Phospho-PKA

PRX:

Peroxiredoxin

PUFA:

Polyunsaturated fatty acids

RF:

Radio frequency

ROOH:

Hydroperoxide

ROS:

Reactive oxygen species

SCI:

Spinal cord injury

SDF:

Sperm DNA fragmentation

SH-:

Sulfhydryl groups

SOD:

Superoxide dismutase

SOD3:

Extracellular SOD

TAC:

Total antioxidant capacity

TNF-α:

Tumor necrosis factor alpha

TRX:

Thioredoxin

References

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

    PubMed  PubMed Central  Google Scholar 

  2. Agarwal A, Prabakaran S, Allamaneni SS (2006) Relationship between oxidative stress, varicocele and infertility: a meta-analysis. Reprod Biomed Online 12(5):630–633

    CAS  PubMed  Google Scholar 

  3. Wagner H, Cheng JW, Ko EY (2018) Role of reactive oxygen species in male infertility: an updated review of literature. Arab J Urol 16(1):35–43

    PubMed  Google Scholar 

  4. Bui A, Sharma R, Henkel R, Agarwal A (2018) Reactive oxygen species impact on sperm DNA and its role in male infertility. Andrologia 50(8):e13012

    CAS  PubMed  Google Scholar 

  5. Gogol P, Szczęśniak-Fabiańczyk B, Wierzchoś-Hilczer A (2009) The photon emission, ATP level and motility of boar spermatozoa during liquid storage. Reprod Biol 9(1):39–49

    PubMed  Google Scholar 

  6. Darbandi M, Darbandi S, Agarwal A, Sengupta P, Durairajanayagam D, Henkel R, Sadeghi MR (2018) Reactive oxygen species and male reproductive hormones. Reprod Biol Endocrinol 16(1):87

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Tremellen K (2008) Oxidative stress and male infertility—a clinical perspective. Hum Reprod Update 14(3):243–258

    CAS  PubMed  Google Scholar 

  8. Nakamura BN, Lawson G, Chan JY, Banuelos J, Cortés MM, Hoang YD, Ortiz L, Rau BA, Luderer U (2010) Knockout of the transcription factor NRF2 disrupts spermatogenesis in an age-dependent manner. Free Radic Biol Med 49(9):1368–1379

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Meseguer M, Antonio Martinez-Conejero J, Muriel L, Pellicer A, Remohí J, Garrido N (2007) The human sperm glutathione system: a key role in male fertility and successful cryopreservation. Drug Metab Lett 1(2):121–126

    CAS  PubMed  Google Scholar 

  10. Alahmar AT (2018) The effects of oral antioxidants on the semen of men with idiopathic oligoasthenoteratozoospermia. Clin Exp Reprod Med 45(2):57–66

    PubMed  PubMed Central  Google Scholar 

  11. Agarwal A, Rana M, Qiu E, AlBunni H, Bui AD, Henkel R (2018) Role of oxidative stress, infection and inflammation in male infertility. Andrologia 50(11):e13126

    PubMed  Google Scholar 

  12. Leclerc P, De Lamirande E, Gagnon C (1997) Regulation of protein-tyrosine phosphorylation and human sperm capacitation by reactive oxygen derivatives. Free Radic Biol Med 22(4):643–656

    CAS  PubMed  Google Scholar 

  13. de Lamirande EHA, Gagnon C (1998) Human sperm capacitation induced by biological fluids and progesterone, but not by NADH or NADPH, is associated with the production of superoxide anion. J Androl 19(2):215–225

    PubMed  Google Scholar 

  14. Herrero MB, de Lamirande E, Gagnon C (1999) Nitric oxide regulates human sperm capacitation and protein-tyrosine phosphorylation in vitro. Biol Reprod 61(3):575–581

    CAS  PubMed  Google Scholar 

  15. Thundathil J, de Lamirande E, Gagnon C (2003) Nitric oxide regulates the phosphorylation of the threonine-glutamine-tyrosine motif in proteins of human spermatozoa during capacitation. Biol Reprod 68(4):1291–1298

    CAS  PubMed  Google Scholar 

  16. Cn O’Flaherty, de Lamirande E, Gagnon C (2005) Reactive oxygen species and protein kinases modulate the level of phospho-MEK-like proteins during human sperm capacitation. Biol Reprod 73(1):94–105

    Google Scholar 

  17. O’Flaherty C, de Lamirande E, Gagnon C (2006) Reactive oxygen species modulate independent protein phosphorylation pathways during human sperm capacitation. Free Radical Biol Med 40(6):1045–1055

    Google Scholar 

  18. Leclerc P, de Lamirande EVE, Gagnon C (1998) Interaction between Ca2+, cyclic 3′, 5′adenosine monophosphate, the superoxide anion, and tyrosine phosphorylation pathways in the regulation of human sperm capacitation. J Androl 19(4):434–443

    CAS  PubMed  Google Scholar 

  19. Lefièvre L, Jha KN, de Lamirande E, Visconti PE, Gagnon C (2002) Activation of protein kinase A during human sperm capacitation and acrosome reaction. J Androl 23(5):709–716

    PubMed  Google Scholar 

  20. Condorelli R, Russo GI, Calogero A, Morgia G, La Vignera S (2017) Chronic prostatitis and its detrimental impact on sperm parameters: a systematic review and meta-analysis. J Endocrinol Invest 40(11):1209–1218

    CAS  PubMed  Google Scholar 

  21. Harlev A, Agarwal A, Gunes SO, Shetty A, du Plessis SS (2015) Smoking and male infertility: an evidence-based review. World J Mens Health 33(3):143–160

    PubMed  PubMed Central  Google Scholar 

  22. Gomez E, Buckingham DW, Brindle J, Lanzafame F, Irvine DS, Aitken RJ (1996) Development of an image analysis system to monitor the retention of residual cytoplasm by human spermatozoa: correlation with biochemical markers of the cytoplasmic space, oxidative stress, and sperm function. J Androl 17(3):276–287

    CAS  PubMed  Google Scholar 

  23. Said TM, Agarwal A, Sharma RK, Mascha E, Sikka SC, Thomas AJ Jr (2004) Human sperm superoxide anion generation and correlation with semen quality in patients with male infertility. Fertil Steril 82(4):871–877

    CAS  PubMed  Google Scholar 

  24. Styrna J, Piasecka M, Malek P, Golas A (2010) Sperm mitochondria diaphorase activity–a gene mapping study of recombinant inbred strains of mice. Int J Dev Biol 54(4):667–673

    PubMed  Google Scholar 

  25. Sabeti P, Pourmasumi S, Rahiminia T, Akyash F, Talebi AR (2016) Etiologies of sperm oxidative stress. Int J Reprod Biomed 14(4):231

    CAS  Google Scholar 

  26. Cooper TG, Noonan E, Von Eckardstein S, Auger J, Baker H, Behre HM, Haugen TB, Kruger T, Wang C, Mbizvo MT (2010) World Health Organization reference values for human semen characteristics. Hum Reprod Update 16(3):231–245

    PubMed  Google Scholar 

  27. Fariello RM, Del Giudice PT, Spaine DM, Fraietta R, Bertolla RP, Cedenho AP (2009) Effect of leukocytospermia and processing by discontinuous density gradient on sperm nuclear DNA fragmentation and mitochondrial activity. J Assist Reprod Genet 26(2–3):151–157

    PubMed  PubMed Central  Google Scholar 

  28. Yadav SB, Suryakar AN, Huddedar AD, Shukla PS (2006) Effect of antioxidants and antibiotics on levels of seminal oxidative stress in leukocytospermic infertile men. Indian J Clin Biochem 21(1):152

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Makker K, Agarwal A, Sharma R (2009) Oxidative stress & male infertility. Indian J Med Res 129(4):357–368

    CAS  PubMed  Google Scholar 

  30. Hamada A, Agarwal A, Sharma R, French DB, Ragheb A, Sabanegh ES Jr (2011) Empirical treatment of low-level leukocytospermia with doxycycline in male infertility patients. Urology 78(6):1320–1325

    PubMed  Google Scholar 

  31. Aboulmaouahib S, Madkour A, Kaarouch I, Sefrioui O, Saadani B, Copin H, Benkhalifa M, Louanjli N, Cadi R (2018) Impact of alcohol and cigarette smoking consumption in male fertility potential: looks at lipid peroxidation, enzymatic antioxidant activities and sperm DNA damage. Andrologia 50(3):e12926

    Google Scholar 

  32. Brand JS, Chan M-F, Dowsett M, Folkerd E, Wareham NJ, Luben RN, van der Schouw YT, Khaw K-T (2011) Cigarette smoking and endogenous sex hormones in postmenopausal women. J Clin Endocrinol Metab 96(10):3184–3192

    CAS  PubMed  Google Scholar 

  33. Valavanidis A, Vlachogianni T, Fiotakis K (2009) Tobacco smoke: involvement of reactive oxygen species and stable free radicals in mechanisms of oxidative damage, carcinogenesis and synergistic effects with other respirable particles. Int J Environ Res Public Health 6(2):445–462

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Ghaffari MA, Rostami M (2013) The effect of cigarette smoking on human sperm creatine kinase activity: as an ATP buffering system in sperm. Int J Fertil Steril 6(4):258

    PubMed  PubMed Central  Google Scholar 

  35. Hamad M, Shelko N, Kartarius S, Montenarh M, Hammadeh M (2014) Impact of cigarette smoking on histone (H2B) to protamine ratio in human spermatozoa and its relation to sperm parameters. Andrology 2(5):666–677

    CAS  PubMed  Google Scholar 

  36. Cui X, Jing X, Wu X, Wang Z, Li Q (2016) Potential effect of smoking on semen quality through DNA damage and the downregulation of Chk1 in sperm. Mol Med Rep 14(1):753–761

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Guthauser B, Boitrelle F, Plat A, Thiercelin N, Vialard F (2013) Chronic excessive alcohol consumption and male fertility: a case report on reversible azoospermia and a literature review. Alcohol Alcohol 49(1):42–44

    PubMed  Google Scholar 

  38. Akang EN, Oremosu AA, Osinubi AA, James AB, Biose IJ, Dike SI, Idoko KM (2017) Alcohol-induced male infertility: is sperm DNA fragmentation a causative? J Exp Clin Anat 16(1):53

    Google Scholar 

  39. Manzo-Avalos S, Saavedra-Molina A (2010) Cellular and mitochondrial effects of alcohol consumption. Int J Environ Res Public Health 7(12):4281–4304

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Bailey SM, Robinson G, Pinner A, Chamlee L, Ulasova E, Pompilius M, Page G, Chhieng D, Jhala N, Landar A (2006) S-Adenosylmethionine prevents chronic alcohol-induced mitochondrial dysfunction in rat liver. Am J Physiol Gastrointest Liver Physiol 291(5):G857–G867

    CAS  PubMed  Google Scholar 

  41. Radi R, Cassina A, Hodara R, Quijano C, Castro L (2002) Peroxynitrite reactions and formation in mitochondria. Free Radical Biol Med 33(11):1451–1464

    CAS  Google Scholar 

  42. Angelopoulou R, Lavranos G, Manolakou P (2009) ROS in the aging male: model diseases with ROS-related pathophysiology. Reprod Toxicol 28(2):167–171

    CAS  PubMed  Google Scholar 

  43. Kesari KK, Agarwal A, Henkel R (2018) Radiations and male fertility. Reprod Biol Endocrinol 16(1):118

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Gautam R, Singh KV, Nirala J, Murmu NN, Meena R, Rajamani P (2018) Oxidative stress-mediated alterations on sperm parameters in male Wistar rats exposed to 3G mobile phone radiation. Andrologia 51(3):e13201

    PubMed  Google Scholar 

  45. Desai NR, Kesari KK, Agarwal A (2009) Pathophysiology of cell phone radiation: oxidative stress and carcinogenesis with focus on male reproductive system. Reprod Biol Endocrinol 7(1):114

    PubMed  PubMed Central  Google Scholar 

  46. Aitken RJ, Gibb Z, Baker MA, Drevet J, Gharagozloo P (2016) Causes and consequences of oxidative stress in spermatozoa. Reprod Fertil Dev 28(1–2):1–10

    CAS  PubMed  Google Scholar 

  47. Chauhan P, Verma HN, Sisodia R, Kesari KK (2017) Microwave radiation (2.45 GHz)-induced oxidative stress: whole-body exposure effect on histopathology of Wistar rats. Electromagn Biol Med 36(1):20–30

    CAS  PubMed  Google Scholar 

  48. Kesari KK, Kumar S, Behari J (2011) 900-MHz microwave radiation promotes oxidation in rat brain. Electromagn Biol Med 30(4):219–234

    CAS  PubMed  Google Scholar 

  49. Du Plessis SS, Agarwal A, Sabanegh Jr ES (2014) Male infertility: a complete guide to lifestyle and environmental factors. Springer, New York, pp 1–268

    Google Scholar 

  50. Sabés-Alsina M, Tallo-Parra O, Mogas MT, Morrell JM, Lopez-Bejar M (2016) Heat stress has an effect on motility and metabolic activity of rabbit spermatozoa. Anim Reprod Sci 173:18–23

    PubMed  Google Scholar 

  51. Pérez-Crespo M, Pintado B, Gutiérrez-Adán A (2008) Scrotal heat stress effects on sperm viability, sperm DNA integrity, and the offspring sex ratio in mice. Mol Reprod Dev 75(1):40–47

    PubMed  Google Scholar 

  52. Paul C, Teng S, Saunders PT (2009) A single, mild, transient scrotal heat stress causes hypoxia and oxidative stress in mouse testes, which induces germ cell death. Biol Reprod 80(5):913–919

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Zhang M, Jiang M, Bi Y, Zhu H, Zhou Z, Sha J (2012) Autophagy and apoptosis act as partners to induce germ cell death after heat stress in mice. PLoS One 7(7):e41412

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Li Y, Cao Y, Wang F, Li C (2014) Scrotal heat induced the Nrf2-driven antioxidant response during oxidative stress and apoptosis in the mouse testis. Acta Histochem 116(5):883–890

    CAS  PubMed  Google Scholar 

  55. Pereira C, Mapuskar K, Rao CV (2006) Chronic toxicity of diethyl phthalate in male Wistar rats—A dose–response study. Regul Toxicol Pharmacol 45(2):169–177

    CAS  PubMed  Google Scholar 

  56. Hauser R, Meeker J, Singh N, Silva M, Ryan L, Duty S, Calafat A (2006) DNA damage in human sperm is related to urinary levels of phthalate monoester and oxidative metabolites. Hum Reprod 22(3):688–695

    PubMed  Google Scholar 

  57. Pant N, Shukla M, Patel DK, Shukla Y, Mathur N, Gupta YK, Saxena DK (2008) Correlation of phthalate exposures with semen quality. Toxicol Appl Pharmacol 231(1):112–116

    CAS  PubMed  Google Scholar 

  58. Radwan M, Jurewicz J, Polańska K, Sobala W, Radwan P, Bochenek M, Hanke W (2016) Exposure to ambient air pollution-does it affect semen quality and the level of reproductive hormones? Ann Hum Biol 43(1):50–56

    PubMed  Google Scholar 

  59. Kampa M, Castanas E (2008) Human health effects of air pollution. Environ Pollut 151(2):362–367

    CAS  PubMed  Google Scholar 

  60. Hsu P-C, Guo YL (2002) Antioxidant nutrients and lead toxicity. Toxicology 180(1):33–44

    CAS  PubMed  Google Scholar 

  61. Acharya U, Acharya S, Mishra M (2003) Lead acetate induced cytotoxicity in male germinal cells of Swiss mice. Ind Health 41(3):291–294

    CAS  PubMed  Google Scholar 

  62. Xu D-X, Shen H-M, Zhu Q-X, Chua L, Wang Q-N, Chia S-E, Ong C-N (2003) The associations among semen quality, oxidative DNA damage in human spermatozoa and concentrations of cadmium, lead and selenium in seminal plasma. Mutat Res Genet Toxicol Environ Mutagen 534(1–2):155–163

    CAS  Google Scholar 

  63. Storgaard L, Bonde JP, Ernst E, Andersen CY, Spano M, Christensen K, Petersen HC, Olsen J (2006) Genetic and environmental correlates of semen quality: a twin study. Epidemiology 17(6):674–681

    PubMed  Google Scholar 

  64. Mobasseri N, Babaei F, Karimian M, Nikzad H (2018) Androgen receptor (AR)-CAG trinucleotide repeat length and idiopathic male infertility: a case-control trial and a meta-analysis. Excli J 17:1167–1179

    PubMed  PubMed Central  Google Scholar 

  65. Rafatmanesh A, Nikzad H, Ebrahimi A, Karimian M, Zamani T (2018) Association of the c.-9C> T and c.368A> G transitions in H2BFWT gene with male infertility in an Iranian population. Andrologia 50(1):e12805

    Google Scholar 

  66. Yu B, Huang Z (2015) Variations in antioxidant genes and male infertility. Biomed Res Int 2015:513196

    PubMed  PubMed Central  Google Scholar 

  67. Holland R, Fishbein JC (2010) Chemistry of the cysteine sensors in Kelch-like ECH-associated protein 1. Antioxid Redox Signal 13(11):1749–1761

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Chan K, Lu R, Chang JC, Kan YW (1996) NRF2, a member of the NFE2 family of transcription factors, is not essential for murine erythropoiesis, growth, and development. Proc Natl Acad Sci USA 93(24):13943–13948

    CAS  PubMed  Google Scholar 

  69. Chyra-Jach D, Kaletka Z, Dobrakowski M (2018) The associations between infertility and antioxidants, proinflammatory cytokines, and chemokines. Oxidative Med Cell Longev 2018:8354747

    Google Scholar 

  70. Aitken RJ, Buckingham DW, Carreras A, Irvine DS (1996) Superoxide dismutase in human sperm suspensions: relationship with cellular composition, oxidative stress, and sperm function. Free Radic Biol Med 21(4):495–504

    CAS  PubMed  Google Scholar 

  71. Faure C, Leveille P, Dupont C, Julia C, Chavatte-Palmer P, Sutton A, Levy R (2014) Are superoxide dismutase 2 and nitric oxide synthase polymorphisms associated with idiopathic infertility? Antioxid Redox Signal 21(4):565–569

    CAS  PubMed  Google Scholar 

  72. Sabouhi S, Salehi Z, Bahadori M, Mahdavi M (2015) Human catalase gene polymorphism (CAT C-262 T) and risk of male infertility. Andrologia 47(1):97–101

    CAS  PubMed  Google Scholar 

  73. Tefik T, Kucukgergin C, Sanli O, Oktar T, Seckin S, Ozsoy C (2013) Manganese superoxide dismutase Ile58Thr, catalase C-262 T and myeloperoxidase G-463 A gene polymorphisms in patients with prostate cancer: relation to advanced and metastatic disease. BJU Int 112(4):E406–E414

    CAS  PubMed  Google Scholar 

  74. Selvaratnam JS, Robaire B (2016) Effects of aging and oxidative stress on spermatozoa of superoxide-dismutase 1-and catalase-null mice. Biol Reprod 95(3):60

    PubMed  PubMed Central  Google Scholar 

  75. Willoughby DS, Hwang P, Willoughby DS (2015) Intracellular mechanistic role of nitric oxide: a comparative analysis of the effectiveness of l-arginine and l-citrulline supplementation on nitric oxide synthesis and subsequent exercise performance in humans. J Food Sci Nutr 2(1):1–8

    Google Scholar 

  76. Stuehr DJ, Griffith OW (1992) Mammalian nitric oxide synthases. Adv Enzymol Relat Areas Mol Biol 65:287–346

    CAS  PubMed  Google Scholar 

  77. Doshi SB, Khullar K, Sharma RK, Agarwal A (2012) Role of reactive nitrogen species in male infertility. Reprod Biol Endocrinol 10(1):109

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Mostafa T, Rashed LA, Nabil N, Fouad H, Sabry D, El-Saied DM (2015) Endothelial nitric oxide synthase gene polymorphism relationship with semen parameters and oxidative stress in infertile oligoasthenoteratozoospermic men. Urology 85(5):1058–1061

    PubMed  Google Scholar 

  79. Oakley A (2011) Glutathione transferases: a structural perspective. Drug Metab Rev 43(2):138–151

    CAS  PubMed  Google Scholar 

  80. Udomsinprasert R, Pongjaroenkit S, Wongsantichon J, Oakley AJ, Prapanthadara L-a, Wilce MC, Ketterman AJ (2005) Identification, characterization and structure of a new Delta class glutathione transferase isoenzyme. Biochem J 388(3):763–771

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Safarinejad MR, Shafiei N, Safarinejad S (2010) The association of glutathione-S-transferase gene polymorphisms (GSTM1, GSTT1, GSTP1) with idiopathic male infertility. J Hum Genet 55(9):565

    CAS  PubMed  Google Scholar 

  82. Xiong D-K, Chen H-H, Ding X-P, Zhang S-H, Zhang J-H (2015) Association of polymorphisms in glutathione S-transferase genes (GSTM1, GSTT1, GSTP1) with idiopathic azoospermia or oligospermia in Sichuan. China Asian J Androl 17(3):481

    CAS  PubMed  Google Scholar 

  83. Arnér ES, Holmgren A (2000) Physiological functions of thioredoxin and thioredoxin reductase. Eur J Biochem 267(20):6102–6109

    PubMed  Google Scholar 

  84. Hansen JM, Go Y-M, Jones DP (2006) Nuclear and mitochondrial compartmentation of oxidative stress and redox signaling. Annu Rev Pharmacol Toxicol 46:215–234

    CAS  PubMed  Google Scholar 

  85. Drevet JR (2006) The antioxidant glutathione peroxidase family and spermatozoa: a complex story. Mol Cell Endocrinol 250(1–2):70–79

    CAS  PubMed  Google Scholar 

  86. Schneider M, Förster H, Boersma A, Seiler A, Wehnes H, Sinowatz F, Neumüller C, Deutsch MJ, Walch A, Hrabé de Angelis M (2009) Mitochondrial glutathione peroxidase 4 disruption causes male infertility. FASEB J 23(9):3233–3242

    CAS  PubMed  Google Scholar 

  87. Chabory E, Damon C, Lenoir A, Kauselmann G, Kern H, Zevnik B, Garrel C, Saez F, Cadet R, Henry-Berger J (2009) Epididymis seleno-independent glutathione peroxidase 5 maintains sperm DNA integrity in mice. J Clin Invest 119(7):2074–2085

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Salimi S, Keshavarzi F, Mohammadpour-Gharehbagh A, Moodi M, Mousavi M, Karimian M, Sandoughi M (2017) Polymorphisms of the folate metabolizing enzymes: association with SLE susceptibility and in silico analysis. Gene 637:161–172

    CAS  PubMed  Google Scholar 

  89. Bafrani HH, Ahmadi M, Jahantigh D, Karimian M (2019) Association analysis of the common varieties of IL17A and IL17F genes with the risk of knee osteoarthritis. J Cell Biochem. https://doi.org/10.1002/jcb.29105

    Article  PubMed  Google Scholar 

  90. Karimian M, Aftabi Y, Mazoochi T, Babaei F, Khamechian T, Boojari H, Nikzad H (2018) Survivin polymorphisms and susceptibility to prostate cancer: a genetic association study and an in silico analysis. EXCLI J 17:479–491

    PubMed  PubMed Central  Google Scholar 

  91. Nejati M, Atlasi MA, Karimian M, Nikzad H, Tameh AA (2018) Lipoprotein lipase gene polymorphisms as risk factors for stroke: a computational and meta-analysis. Iran J Basic Med Sci 21(7):701–708

    PubMed  PubMed Central  Google Scholar 

  92. Mobasseri N, Nikzad H, Karimian M (2019) Protective effect of estrogen receptor alpha-PvuII transition against idiopathic male infertility: a case-control study and meta-analysis. Reprod Biomed Online 38(4):588–598

    CAS  PubMed  Google Scholar 

  93. Noureddini M, Mobasseri N, Karimian M, Behjati M, Nikzad H (2018) Arg399Gln substitution in XRCC1 as a prognostic and predictive biomarker for prostate cancer: evidence from 8662 subjects and a structural analysis. J Gene Med 20(10–11):e3053

    PubMed  Google Scholar 

  94. Tameh AA, Karimian M, Zare-Dehghanani Z, Aftabi Y, Beyer C (2018) Role of steroid therapy after ischemic stroke by N-methyl-d-aspartate receptor gene regulation. J Stroke Cerebrovasc Dis 27(11):3066–3075

    PubMed  Google Scholar 

  95. Behrouzi S, Mashayekhi F, Bahadori MH (2018) The association of PON1 192 Q/R polymorphism with the risk of idiopathic male infertility in northern Iran. Avicenna J Med Biotechnol 11(1):253–256

    Google Scholar 

  96. Garcia Rodriguez A, de la Casa M, Johnston S (2019) Association of polymorphisms in genes coding for antioxidant enzymes and human male infertility. Ann Hum Genet 83(1):63–72

    CAS  PubMed  Google Scholar 

  97. Vučić N, Nikolić Z, Vukotić V, Tomović S, Vuković I, Kanazir S, Savić-Pavićević D, Brajušković G (2018) NOS 3 gene variants and male infertility: association of 4a/4b with oligoasthenozoospermia. Andrologia 50(1):e12817

    Google Scholar 

  98. Mazjin M, Salehi Z, Mashayekhi F, Bahadori M (2016) Evaluation of GPx1 Pro198Leu polymorphism in idiopathic male infertility. Mol Biol 50(1):77–80

    CAS  Google Scholar 

  99. Yan L, Guo W, Wu S, Liu J, Zhang S, Shi L, Ji G, Gu A (2014) Genetic variants in nitric oxide synthase genes and the risk of male infertility in a Chinese population: a case-control study. PLoS One 9(12):e115190

    PubMed  PubMed Central  Google Scholar 

  100. Ji G, Yan L, Liu W, Qu J, Gu A (2013) OGG1 Ser326Cys polymorphism interacts with cigarette smoking to increase oxidative DNA damage in human sperm and the risk of male infertility. Toxicol Lett 218(2):144–149

    CAS  PubMed  Google Scholar 

  101. Kolesnikova L, Kurashova N, Bairova T, Dolgikh M, Ershova O, Natyaganova L, Dashiev B, Gutnik I, Koroleva N (2017) Features of lipoperoxidation, antioxidant defense, and thiol/disulfide system in the pathogenesis of infertility in males, carriers of nonfunctional variants of GSTT1 and GSTM1 gene polymorphisms. Bull Exp Biol Med 163(3):378–380

    CAS  PubMed  Google Scholar 

  102. Hashad D, Mohamed N, Hashad M (2012) Luteinising hormone β-subunit gene Gly102Ser variant and oxidative stress biomarkers in Egyptian infertile males. Andrologia 44:484–489

    PubMed  Google Scholar 

  103. Liu H, Zhao J, Xu J, Zhu P, Yu M, Jiang W, Zhang J, Li W, Wu Q, Li Z (2018) Correlation of the single nucleotide polymorphism rs662 of PON1 with the risk of male infertility. Zhonghua Nan Ke Xue 24(8):708–712

    PubMed  Google Scholar 

  104. Trang NT, Huyen VT, Tuan NT, Phan TD (2018) Association of N-acetyltransferase-2 and glutathione S-transferase polymorphisms with idiopathic male infertility in Vietnam male subjects. Chem Biol Interact 286:11–16

    PubMed  Google Scholar 

  105. Inbar-Feigenberg M, Choufani S, Butcher DT, Roifman M, Weksberg R (2013) Basic concepts of epigenetics. Fertil Steril 99(3):607–615

    CAS  PubMed  Google Scholar 

  106. Feinberg AP, Cui H, Ohlsson R (2002) DNA methylation and genomic imprinting: insights from cancer into epigenetic mechanisms. Semin Cancer Biol 12(5):389–398

    CAS  PubMed  Google Scholar 

  107. Jue K, Benoit G, Alcivar-Warren AA, Trasler JM (1995) Developmental and hormonal regulation of DNA methyltransferase in the rat testis. Biol Reprod 52:1364–1371

    CAS  PubMed  Google Scholar 

  108. Omisanjo OA, Biermann K, Hartmann S, Heukamp LC, Sonnack V, Hild A, Brehm R, Bergmann M, Weidner W, Steger K (2007) DNMT1 and HDAC1 gene expression in impaired spermatogenesis and testicular cancer. Histochem Cell Biol 127(2):175–181

    CAS  PubMed  Google Scholar 

  109. Ariel M, Cedar H, McCarrey J (1994) Developmental changes in methylation of spermatogenesis–specific genes include reprogramming in the epididymis. Nat Genet 7(1):59

    CAS  PubMed  Google Scholar 

  110. Olszewska M, Barciszewska MZ, Fraczek M, Huleyuk N, Chernykh VB, Zastavna D, Barciszewski J, Kurpisz M (2017) Global methylation status of sperm DNA in carriers of chromosome structural aberrations. Asian J Androl 19(1):117

    CAS  PubMed  Google Scholar 

  111. Tunc O, Tremellen K (2009) Oxidative DNA damage impairs global sperm DNA methylation in infertile men. J Assist Reprod Genet 26(9–10):537–544

    PubMed  PubMed Central  Google Scholar 

  112. Franco R, Schoneveld O, Georgakilas AG, Panayiotidis MI (2008) Oxidative stress, DNA methylation and carcinogenesis. Cancer lett 266(1):6–11

    CAS  PubMed  Google Scholar 

  113. Hepburn P, Margison G, Tisdale M (1991) Enzymatic methylation of cytosine in DNA is prevented by adjacent O6-methylguanine residues. J Biol Chem 266(13):7985–7987

    CAS  PubMed  Google Scholar 

  114. Turk PW, Laayoun A, Smith SS, Weitzman SA (1995) DNA adduct 8-hydroxyl-2′-deoxyguanosine (8-hydroxyguanine) affects function of human DNA methyltransferase. Carcinogenesis 16(5):1253–1255

    CAS  PubMed  Google Scholar 

  115. Yi P, Melnyk S, Pogribna M, Pogribny IP, Hine RJ, James SJ (2000) Increase in plasma homocysteine associated with parallel increases in plasma S-adenosylhomocysteine and lymphocyte DNA hypomethylation. J Biol Chem 275(38):29318–29323

    CAS  PubMed  Google Scholar 

  116. Jamaluddin MS, Chen I, Yang F, Jiang X, Jan M, Liu X, Schafer AI, Durante W, Yang X, Wang H (2007) Homocysteine inhibits endothelial cell growth via DNA hypomethylation of the cyclin Agene. Blood 110(10):3648–3655

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Karimian M, Hosseinzadeh Colagar A (2018) Human MTHFR-G1793A transition may be a protective mutation against male infertility: a genetic association study and in silico analysis. Hum Fertil 21(2):128–136

    CAS  Google Scholar 

  118. Aitken RJ, Curry BJ (2011) Redox regulation of human sperm function: from the physiological control of sperm capacitation to the etiology of infertility and DNA damage in the germ line. Antioxid Redox Signal 14(3):367–381

    CAS  PubMed  Google Scholar 

  119. Noblanc A, Damon-Soubeyrand C, Karrich B, Henry-Berger J, Cadet R, Saez F, Guiton R, Janny L, Pons-Rejraji H, Alvarez JG (2013) DNA oxidative damage in mammalian spermatozoa: where and why is the male nucleus affected? Free Radical Biol Med 65:719–723

    CAS  Google Scholar 

  120. Ohno M, Sakumi K, Fukumura R, Furuichi M, Iwasaki Y, Hokama M, Ikemura T, Tsuzuki T, Gondo Y, Nakabeppu Y (2014) 8-Oxoguanine causes spontaneous de novo germline mutations in mice. Sci Rep 4:4689

    PubMed  PubMed Central  Google Scholar 

  121. Muratori M, Tamburrino L, Marchiani S, Cambi M, Olivito B, Azzari C, Forti G, Baldi E (2015) Investigation on the origin of sperm DNA fragmentation: role of apoptosis, immaturity and oxidative stress. Mol Med 21(1):109–122

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Bauer NC, Corbett AH, Doetsch PW (2015) The current state of eukaryotic DNA base damage and repair. Nucleic Acids Res 43(21):10083–10101

    CAS  PubMed  PubMed Central  Google Scholar 

  123. Dorostghoal M, Kazeminejad S, Shahbazian N, Pourmehdi M, Jabbari A (2017) Oxidative stress status and sperm DNA fragmentation in fertile and infertile men. Andrologia 49(10):e12762

    Google Scholar 

  124. Aitken R, Smith T, Lord T, Kuczera L, Koppers A, Naumovski N, Connaughton H, Baker M, De Iuliis G (2013) On methods for the detection of reactive oxygen species generation by human spermatozoa: analysis of the cellular responses to catechol oestrogen, lipid aldehyde, menadione and arachidonic acid. Andrology 1(2):192–205

    CAS  PubMed  Google Scholar 

  125. Gaschler MM, Stockwell BR (2017) Lipid peroxidation in cell death. Biochem Biophys Res Commun 482(3):419–425

    CAS  PubMed  PubMed Central  Google Scholar 

  126. Saleh RA, Ashok Agarwal HCLD (2002) Oxidative stress and male infertility: from research bench to clinical practice. J Androl 23(6):737–752

    CAS  PubMed  Google Scholar 

  127. Aitken RJ, Whiting S, De Iuliis GN, McClymont S, Mitchell LA, Baker MA (2012) Electrophilic aldehydes generated by sperm metabolism activate mitochondrial reactive oxygen species generation and apoptosis by targeting succinate dehydrogenase. J Biol Chem 287(39):33048–33060

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Talebi E, Karimian M, Nikzad H (2018) Association of sperm mitochondrial DNA deletions with male infertility in an Iranian population. Mitochondrial DNA A DNA Mapp Seq Anal 29(4):615–623

    CAS  PubMed  Google Scholar 

  129. Moretti E, Collodel G, Fiaschi AI, Micheli L, Iacoponi F, Cerretani D (2017) Nitric oxide, malondialdheyde and non-enzymatic antioxidants assessed in viable spermatozoa from selected infertile men. Reprod Biol 17(4):370–375

    PubMed  Google Scholar 

  130. Turner TT, Bang HJ, Lysiak JJ (2005) Experimental testicular torsion: reperfusion blood flow and subsequent testicular venous plasma testosterone concentrations. Urology 65(2):390–394

    PubMed  Google Scholar 

  131. Hanukoglu I (2006) Antioxidant protective mechanisms against reactive oxygen species (ROS) generated by mitochondrial P450 systems in steroidogenic cells. Drug Metab Rev 38(1–2):171–196

    CAS  PubMed  Google Scholar 

  132. Aitken RJ, Baker MA, Sawyer D (2003) Oxidative stress in the male germ line and its role in the aetiology of male infertility and genetic disease. Reprod Biomed Online 7(1):65–70

    CAS  PubMed  Google Scholar 

  133. Mancini A, Leone E, Festa R, Grande G, Silvestrini A, De Marinis L, Pontecorvi A, Maira G, Littarru GP, Meucci E (2008) Effects of testosterone on antioxidant systems in male secondary hypogonadism. J Androl 29(6):622–629

    CAS  PubMed  Google Scholar 

  134. Shang X, Huang Y, Ye Z, Yu X, Gu W (2004) Protection of melatonin against damage of sperm mitochondrial function induced by reactive oxygen species. Zhonghua Nan Ke Xue 10(8):604–607

    CAS  PubMed  Google Scholar 

  135. Adewoyin M, Mohsin SMN, Arulselvan P, Hussein MZ, Fakurazi S (2015) Enhanced anti-inflammatory potential of cinnamate-zinc layered hydroxide in lipopolysaccharide-stimulated RAW 264.7 macrophages. Drug Des Devel Ther 9:2475

    CAS  PubMed  PubMed Central  Google Scholar 

  136. Sarkar O, Bahrainwala J, Chandrasekaran S, Kothari S, Mathur PP, Agarwal A (2011) Impact of inflammation on male fertility. Front Biosci (Elite Ed) 3:89–95

    Google Scholar 

  137. Liew SH, Meachem SJ, Hedger MP (2007) A stereological analysis of the response of spermatogenesis to an acute inflammatory episode in adult rats. J Androl 28(1):176–185

    PubMed  Google Scholar 

  138. Pasqualotto FF, Sharma RK, Potts JM, Nelson DR, Thomas AJ Jr, Agarwal A (2000) Seminal oxidative stress in patients with chronic prostatitis. Urology 55(6):881–885

    CAS  PubMed  Google Scholar 

  139. Zamani-Badi T, Karimian M, Azami-Tameh A, Nikzad H (2019) Association of C3953T transition in interleukin 1β gene with idiopathic male infertility in an Iranian population. Hum Fertil 22(2):111–117

    CAS  Google Scholar 

  140. Zamani-Badi T, Nikzad H, Karimian M (2018) IL-1RA VNTR and IL-1α 4845G> T polymorphisms and risk of idiopathic male infertility in Iranian men: a case–control study and an in silico analysis. Andrologia 50(9):e13081

    PubMed  Google Scholar 

  141. Azenabor A, Ekun AO, Akinloye O (2015) Impact of inflammation on male reproductive tract. J Reprod Infertil 16(3):123

    PubMed  PubMed Central  Google Scholar 

  142. Agarwal A, Esteves SC (2016) Varicocele and male infertility: current concepts and future perspectives. Asian J Androl 18(2):161

    PubMed  PubMed Central  Google Scholar 

  143. Mostafa T, Anis T, El Nashar A, Imam H, Osman I (2012) Seminal plasma reactive oxygen species–antioxidants relationship with varicocele grade. Andrologia 44(1):66–69

    CAS  PubMed  Google Scholar 

  144. Agarwal A, Hamada A, Esteves SC (2012) Insight into oxidative stress in varicocele-associated male infertility: part 1. Nat Rev Urol 9(12):678

    PubMed  Google Scholar 

  145. Hamada A, Esteves SC, Agarwal A (2013) Insight into oxidative stress in varicocele-associated male infertility: part 2. Nat Rev Urol 10(1):26

    CAS  PubMed  Google Scholar 

  146. Türkyilmaz Z, Gülen Ş, Sönmez K, Karabulut R, Dinçer S, Can Başaklar A, Kale N (2004) Increased nitric oxide is accompanied by lipid oxidation in adolescent varicocele. Int J Androl 27(3):183–187

    PubMed  Google Scholar 

  147. Altunoluk B, Efe E, Kurutas EB, Gul AB, Atalay F, Eren M (2012) Elevation of both reactive oxygen species and antioxidant enzymes in vein tissue of infertile men with varicocele. Urol Int 88(1):102–106

    CAS  PubMed  Google Scholar 

  148. Soubry A, Guo L, Huang Z, Hoyo C, Romanus S, Price T, Murphy SK (2016) Obesity-related DNA methylation at imprinted genes in human sperm: results from the TIEGER study. Clin Epigenetics 8(1):51

    PubMed  PubMed Central  Google Scholar 

  149. Bakos H, Mitchell M, Setchell B, Lane M (2011) The effect of paternal diet-induced obesity on sperm function and fertilization in a mouse model. Int J Androl 34(5pt1):402–410

    CAS  PubMed  Google Scholar 

  150. Garolla A, Torino M, Miola P, Caretta N, Pizzol D, Menegazzo M, Bertoldo A, Foresta C (2015) Twenty-four-hour monitoring of scrotal temperature in obese men and men with a varicocele as a mirror of spermatogenic function. Hum Reprod 30(5):1006–1013

    CAS  PubMed  Google Scholar 

  151. Du Plessis SS, Cabler S, McAlister DA, Sabanegh E, Agarwal A (2010) The effect of obesity on sperm disorders and male infertility. Nat Rev Urol 7(3):153

    PubMed  Google Scholar 

  152. Jia Y-F, Feng Q, Ge Z-Y, Guo Y, Zhou F, Zhang K-S, Wang X-W, Lu W-H, Liang X-W, Gu Y-Q (2018) Obesity impairs male fertility through long-term effects on spermatogenesis. BMC Urol 18(1):42

    PubMed  PubMed Central  Google Scholar 

  153. Adewoyin M, Ibrahim M, Roszaman R, Isa M, Alewi N, Rafa A, Anuar M (2017) Male infertility: the effect of natural antioxidants and phytocompounds on seminal oxidative stress. Diseases 5(1):9

    PubMed Central  Google Scholar 

  154. Walczak-Jedrzejowska R, Wolski JK, Slowikowska-Hilczer J (2013) The role of oxidative stress and antioxidants in male fertility. Cent Eur J Urol 66(1):60

    CAS  Google Scholar 

  155. Esteves SC, Agarwal A (2011) Novel concepts in male infertility. Int Braz J Urol 37(1):5–15

    PubMed  Google Scholar 

  156. Zini A, San Gabriel M, Baazeem A (2009) Antioxidants and sperm DNA damage: a clinical perspective. J Assist Reprod Genet 26(8):427–432

    PubMed  PubMed Central  Google Scholar 

  157. Sengupta P, Agarwal A, Pogrebetskaya M, Roychoudhury S, Durairajanayagam D, Henkel R (2018) Role of Withania somnifera (Ashwagandha) in the management of male infertility. Reprod Biomed Online 36(3):311–326

    PubMed  Google Scholar 

  158. Fujii J, Iuchi Y, Matsuki S, Ishii T (2003) Cooperative function of antioxidant and redox systems against oxidative stress in male reproductive tissues. Asian J Androl 5(3):231–242

    CAS  PubMed  Google Scholar 

  159. Kobayashi T, Miyazaki T, Natori M, Nozawa S (1991) Protective role of superoxide dismutase in human sperm motifity: superoxide dismutase activity and lipid peroxide in human seminal plasma and spermatozoa. Hum Reprod 6(7):987–991

    CAS  PubMed  Google Scholar 

  160. Valko M, Rhodes C, Moncol J, Izakovic M, Mazur M (2006) Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 160(1):1–40

    CAS  PubMed  Google Scholar 

  161. Lenzi A, Lombardo F, Sgrò P, Salacone P, Caponecchia L, Dondero F, Gandini L (2003) Use of carnitine therapy in selected cases of male factor infertility: a double-blind crossover trial. Fertil Steril 79(2):292–300

    PubMed  Google Scholar 

  162. Opuwari CS, Henkel RR (2016) An update on oxidative damage to spermatozoa and oocytes. Biomed Res Int 2016:9540142

    PubMed  PubMed Central  Google Scholar 

  163. Ciftci H, Verit A, Savas M, Yeni E, Erel O (2009) Effects of N-acetylcysteine on semen parameters and oxidative/antioxidant status. Urology 74(1):73–76

    PubMed  Google Scholar 

  164. Kefer JC, Agarwal A, Sabanegh E (2009) Role of antioxidants in the treatment of male infertility. Int J Urol 16(5):449–457

    CAS  PubMed  Google Scholar 

  165. Da Silva RF, Borges CdS, Villela e Silva P, Missassi G, Kiguti LRA, Pupo AS, Barbosa Junior F, Anselmo-Franci JA, Kempinas WDG (2016) The coadministration of N-acetylcysteine ameliorates the effects of arsenic trioxide on the male mouse genital system. Oxidative Med Cell Longev 2016:4257498

    Google Scholar 

  166. Bucak MN, Ateşşahin A, Varışlı Ö, Yüce A, Tekin N, Akçay A (2007) The influence of trehalose, taurine, cysteamine and hyaluronan on ram semen: microscopic and oxidative stress parameters after freeze–thawing process. Theriogenology 67(5):1060–1067

    CAS  PubMed  Google Scholar 

  167. Maya-Soriano MJ, Taberner E, Sabes-Alsina M, Lopez-Bejar M (2013) Retinol might stabilize sperm acrosomal membrane in situations of oxidative stress because of high temperatures. Theriogenology 79(2):367–373

    CAS  PubMed  Google Scholar 

  168. Comhaire F, Mahmoud A (2016) The andrologist’s contribution to a better life for ageing men: part 1. Andrologia 48(1):87–98

    CAS  PubMed  Google Scholar 

  169. Jacob RA, Pianalto FS, Agee RE (1992) Cellular ascorbate depletion in healthy men. J Nutr 122(5):1111–1118

    CAS  PubMed  Google Scholar 

  170. Thiele JJ, Friesleben HJ, Fuchs J, Ochsendorf FR (1995) Ascorbic acid and urate in human seminal plasma: determination and interrelationships with chemiluminescence in washed semen. Human Reprod 10(1):110–115

    CAS  Google Scholar 

  171. Song GJ, Norkus EP, Lewis V (2006) Relationship between seminal ascorbic acid and sperm DNA integrity in infertile men. Int J Androl 29(6):569–575

    CAS  PubMed  Google Scholar 

  172. Eskenazi B, Kidd S, Marks A, Sloter E, Block G, Wyrobek A (2005) Antioxidant intake is associated with semen quality in healthy men. Human Reprod 20(4):1006–1012

    CAS  Google Scholar 

  173. Geva E, Bartoov B, Zabludovsky N, Lessing JB, Lerner-Geva L, Amit A (1996) The effect of antioxidant treatment on human spermatozoa and fertilization rate in an in vitro fertilization program. Fertil Steril 66(3):430–434

    CAS  PubMed  Google Scholar 

  174. Suleiman SA, Ali ME, Zaki Z, El-Malik E, Nasr M (1996) Lipid peroxidation and human sperm motility: protective role of vitamin E. J Androl 17(5):530–537

    CAS  PubMed  Google Scholar 

  175. Comhaire F (2010) The role of food supplementation in the treatment of the infertile couple and for assisted reproduction. Andrologia 42(5):331–340

    PubMed  Google Scholar 

  176. Gvozdjáková A, Kucharská J, Dubravicky J, Mojto V, Singh RB (2015) Coenzyme Q10, α-tocopherol, and oxidative stress could be important metabolic biomarkers of male infertility. Dis Markers 2015:827941

    PubMed  PubMed Central  Google Scholar 

  177. Balercia G, Buldreghini E, Vignini A, Tiano L, Paggi F, Amoroso S, Ricciardo-Lamonica G, Boscaro M, Lenzi A, Littarru G (2009) Coenzyme Q10 treatment in infertile men with idiopathic asthenozoospermia: a placebo-controlled, double-blind randomized trial. Fertil Steril 91(5):1785–1792

    CAS  PubMed  Google Scholar 

  178. Safarinejad MR (2012) The effect of coenzyme Q 10 supplementation on partner pregnancy rate in infertile men with idiopathic oligoasthenoteratozoospermia: an open-label prospective study. Int Urol Nephrol 44(3):689–700

    CAS  PubMed  Google Scholar 

  179. Mancini A, Conte G, Milardi D, De Marinis L, Littarru G (1998) Relationship between sperm cell ubiquinone and seminal parameters in subjects with and without varicocele. Andrologia 30(1):1–4

    CAS  PubMed  Google Scholar 

  180. Atig F, Raffa M, Ali HB, Abdelhamid K, Saad A, Ajina M (2012) Altered antioxidant status and increased lipid per-oxidation in seminal plasma of tunisian infertile men. J Hum Reprod Sci 8(1):139

    CAS  Google Scholar 

  181. Agarwal A, Sekhon LH (2011) Oxidative stress and antioxidants for idiopathic oligoasthenoteratospermia: is it justified? Indian J Urol 27(1):74

    PubMed  PubMed Central  Google Scholar 

  182. Greco E, Iacobelli M, Rienzi L, Ubaldi F, Ferrero S, Tesarik J (2005) Reduction of the incidence of sperm DNA fragmentation by oral antioxidant treatment. J Androl 26(3):349–353

    CAS  PubMed  Google Scholar 

  183. Mishra M, Acharya UR (2004) Protective action of vitamins on the spermatogenesis in lead-treated Swiss mice. J Trace Elem Med Biol 18(2):173–178

    CAS  PubMed  Google Scholar 

  184. Aguirre-Arias MV, Velarde V, Moreno RD (2017) Effects of ascorbic acid on spermatogenesis and sperm parameters in diabetic rats. Cell Tissue Res 370(2):305–317

    CAS  PubMed  Google Scholar 

  185. Tahvilzadeh M, Hajimahmoodi M, Toliyat T, Karimi M, Rahimi R (2016) An evidence-based approach to medicinal plants for the treatment of sperm abnormalities in traditional Persian medicine. Andrologia 48(8):860–879

    CAS  PubMed  Google Scholar 

  186. Zhang L, Diao RY, Duan YG, Yi TH, Cai ZM (2017) In vitro antioxidant effect of curcumin on human sperm quality in leucocytospermia. Andrologia 49(10):e12760

    Google Scholar 

  187. Yüce A, Türk G, Çeribaşi S, Sönmez M, Ciftci M, Güvenç M (2013) Effects of cinnamon (Cinnamomum zeylanicum) bark oil on testicular antioxidant values, apoptotic germ cell and sperm quality. Andrologia 45(4):248–255

    PubMed  Google Scholar 

  188. Heidary M, Vahhabi S, Nejadi JR, Delfan B, Birjandi M, Kaviani H, Givrad S (2008) Effect of saffron on semen parameters of infertile men. Urol J 5(4):255–259

    PubMed  Google Scholar 

  189. Safarinejad MR, Shafiei N, Safarinejad S (2011) A prospective double-blind randomized placebo-controlled study of the effect of saffron (Crocus sativus Linn.) on semen parameters and seminal plasma antioxidant capacity in infertile men with idiopathic oligoasthenoteratozoospermia. Phytother Res 25(4):508–516

    CAS  PubMed  Google Scholar 

  190. Kolahdooz M, Nasri S, Modarres SZ, Kianbakht S, Huseini HF (2014) Effects of Nigella sativa L. seed oil on abnormal semen quality in infertile men: a randomized, double-blind, placebo-controlled clinical trial. Phytomedicine 21(6):901–905

    CAS  PubMed  Google Scholar 

  191. Roychoudhury S, Agarwal A, Virk G, Cho C-L (2017) Potential role of green tea catechins in the management of oxidative stress-associated infertility. Reprod Biomed online 34(5):487–498

    CAS  PubMed  Google Scholar 

  192. Omu AE, Al-Azemi MK, Al-Maghrebi M, Mathew CT, Omu FE, Kehinde EO, Anim JT, Oriowo MA, Memon A (2015) Molecular basis for the effects of zinc deficiency on spermatogenesis: an experimental study in the Sprague-dawley rat model. Indian J Urol 31(1):57

    PubMed  PubMed Central  Google Scholar 

  193. Hijazi MM, Khatoon N, Azmi MA, Rajput MT, Zaidi H, Ijaz S, Azmi MA, Perveen R, Naqvi H, Naimul S (2015) Effects of Camellia sinensis L. (green tea) extract on the body and testicular weight changes in adult Wistar rate. Pak J Pharm Sci 28(1):249–253

    PubMed  Google Scholar 

  194. Sakr SA, Zowail ME, Marzouk AM (2014) Effect of saffron (Crocus sativus L.) on sodium valporate induced cytogenetic and testicular alterations in albino rats. Anat Cell Biol 47(3):171–179

    PubMed  PubMed Central  Google Scholar 

  195. Modaresi M, Messripour M, Asadi Marghmaleki M, Hamadanian M (2008) Effect of saffron (Crocus sativus) extract on level of FSH, LH and testosterone in mice. J Adv Med Biomed Res 16(63):11–18

    Google Scholar 

  196. Parandin R, Yousofvand N, Ghorbani R (2012) The enhancing effects of alcoholic extract of Nigella sativa seed on fertility potential, plasma gonadotropins and testosterone in male rats. Iran J Reprod Med 10(4):355

    PubMed  PubMed Central  Google Scholar 

  197. Ashamu E, Salawu E, Oyewo O, Alhassan A, Alamu O, Adegoke A (2010) Efficacy of vitamin C and ethanolic extract of Sesamum indicum in promoting fertility in male Wistar rats. J Hum Reprod Sci 3(1):11

    PubMed  PubMed Central  Google Scholar 

  198. Zarepourfard H, Riasi A, Frouzanfar M, Hajian M, Esfahani MHN (2019) Pomegranate seed in diet, affects sperm parameters of cloned goats following freezing-thawing. Theriogenology 125:203–209

    CAS  PubMed  Google Scholar 

  199. Chenniappan K, Murugan K (2017) Therapeutic and fertility restoration effects of Ionidium suffruticosum on sub-fertile male albino Wistar rats: effects on testis and caudal spermatozoa. Pharm Biol 55(1):946–957

    PubMed  PubMed Central  Google Scholar 

  200. Hala A, Khattab Z, Abdallah G, Kamel M (2010) Grape seed extract alleviate reproductive toxicity caused by aluminium chloride in male rats. J Am Sci 6(12):352–361

    Google Scholar 

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Acknowledgements

This work was supported by grants from the Vice Chancellor for Research and Technology, Kashan University of Medical Sciences, Kashan, Iran.

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  1. Anatomical Sciences Research Center, Kashan University of Medical Sciences, Kashan, Iran

    Erfaneh Barati, Hossein Nikzad & Mohammad Karimian

  2. Gametogenesis Research Center, Kashan University of Medical Sciences, Kashan, Iran

    Hossein Nikzad & Mohammad Karimian

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Barati, E., Nikzad, H. & Karimian, M. Oxidative stress and male infertility: current knowledge of pathophysiology and role of antioxidant therapy in disease management. Cell. Mol. Life Sci. 77, 93–113 (2020). https://doi.org/10.1007/s00018-019-03253-8

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