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Reactive Oxygen Species in the Reproductive System: Sources and Physiological Roles

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Oxidative Stress and Toxicity in Reproductive Biology and Medicine

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1358))

Abstract

Reactive oxygen species (ROS) are oxygen-containing molecules which are reactive in nature and are capable of independent existence in the body. ROS comprise mostly of free radicals that contain at least one unpaired electron. Endogenous sources are the foremost birthplaces of ROS, which include mitochondrial electron transport chain, endoplasmic reticulum and peroxisome. Conversely, numerous enzymatic pathways such as xanthine oxidase and cyclooxygenase systems are among the prominent generators of cellular ROS. Major sources of ROS in the female reproductive tract include Graafian follicles, follicular fluid, fallopian tube, peritoneal cavity and endometrium. On the contrary, leukocytes, immature spermatozoa and varicocele are the key originators of ROS in the male reproductive system. For the sake of maintaining a proper oxidative balance, cells have evolved a variety of antioxidative molecules. From the physiological perspective, ROS and antioxidants are actively involved in the regulation of myriad female reproductive processes, such as cyclic luteal and endometrial changes, follicular development, ovulation, fertilization, embryonic implantation, maintenance of pregnancy and parturition. Similarly, physiological amounts of ROS are crucial in the accomplishment of various male reproductive functions as well, which include spermatozoa maturation, capacitation, hyperactivation and acrosome reaction. This chapter highlights the birthplaces of ROS in the female and male reproductive tract along with mechanisms of their production. This chapter will also put forward specific physiological roles of these reactive molecules in upholding the structural integrity and functionality of both the reproductive systems.

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References

  1. Ray PD, Huang B-W, Tsuji Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signalling. Cell Signal. 2012;24:981–90. https://doi.org/10.1016/j.cellsig.2012.01.008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Snezkina AV, Kudryavtseva AV, Kardymon OL, Savvateeva MV, Melnikova NV, Krasnov GS, Dmitriev AA. ROS generation and antioxidant defence systems in normal and malignant cells. Oxidative Med Cell Longev. 2019;2019:6175804. https://doi.org/10.1155/2019/6175804.

    Article  CAS  Google Scholar 

  3. Agarwal A, Gupta S, Sharma RK. Role of oxidative stress in female reproduction. Reprod Biol Endocrinol. 2005;3:28. https://doi.org/10.1186/1477-7827-3-28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Al-Gubory KH, Fowler PA, Garrel C. The roles of cellular reactive oxygen species, oxidative stress and antioxidants in pregnancy outcomes. Int J Biochem Cell Biol. 2010;42:1634–50. https://doi.org/10.1016/j.biocel.2010.06.001.

    Article  CAS  PubMed  Google Scholar 

  5. Finkel T, Holbrook NJ. Oxidants, oxidative stress and the biology of ageing. Nature. 2000;408:239–47. https://doi.org/10.1038/35041687.

    Article  CAS  PubMed  Google Scholar 

  6. Schieber M, Chandel NS. ROS function in redox signalling and oxidative stress. Curr Biol. 2014;24:R453–62. https://doi.org/10.1016/j.cub.2014.03.034.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ahmad G, Almasry M, Dhillon AS, Abuayyash MM, Kothandaraman N, Cakar Z. Overview and sources of reactive oxygen species (ROS) in the reproductive system. In: Agarwal A, Sharma RK, Gupta S, Harlev A, Ahmad G, du Plessis SS, Esteves SC, Wang SM, Durairajanayagam D, editors. Oxidative stress in human reproduction shedding light on a complicated phenomenon. Springer; 2017. p. 1–16. https://doi.org/10.1007/978-3-319-48427-3_1.

    Chapter  Google Scholar 

  8. Finkel T. Signal transduction by reactive oxygen species. J Cell Biol. 2011;194:7–15. https://doi.org/10.1083/jcb.201102095.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Roychoudhury S, Agarwal A, Virk G, Cho C-L. Potential role of green tea catechins in the management of oxidative stress-associated infertility. Reprod Biomed Online. 2017;34:487–98. https://doi.org/10.1016/j.rbmo.2017.02.006.

    Article  CAS  PubMed  Google Scholar 

  10. Wood ZA, Poole LB, Karplus PA. Peroxiredoxin evolution and the regulation of hydrogen peroxide signalling. Science. 2003;300:650–3. https://doi.org/10.1126/science.1080405.

    Article  CAS  PubMed  Google Scholar 

  11. du Plessis SS, Harlev A, Mohamed MI, Habib E, Kothandaraman N, Cakar Z. Physiological roles of reactive oxygen species (ROS) in the reproductive system. In: Agarwal A, Sharma RK, Gupta S, Harlev A, Ahmad G, du Plessis SS, Esteves SC, Wang SM, Durairajanayagam D, editors. Oxidative stress in human reproduction shedding light on a complicated phenomenon. Springer; 2017. p. 47–64. https://doi.org/10.1007/978-3-319-48427-3_3.

    Chapter  Google Scholar 

  12. Aitken RJ, Clarkson JS, Fishel S. Generation of reactive oxygen species, lipid peroxidation and human sperm function. Biol Reprod. 1989;41:183–97. https://doi.org/10.1095/biolreprod41.1.183.

    Article  CAS  PubMed  Google Scholar 

  13. Martindale JL, Holbrook NJ. Cellular response to oxidative stress: signalling for suicide and survival. J Cell Physiol. 2002;192:1–15. https://doi.org/10.1002/jcp.10119.

    Article  CAS  PubMed  Google Scholar 

  14. Li R, Jia Z, Trush MA. Defining ROS in biology and medicine. React Oxyg Species. 2016;1:9–21. https://doi.org/10.20455/ros.2016.803.

    Article  Google Scholar 

  15. Di Meo S, Reed TT, Venditti P, Victor VM. Role of ROS and RNS sources in physiological and pathological conditions. Oxidative Med Cell Longev. 2016;2016:1245049. https://doi.org/10.1155/2016/1245049.

    Article  CAS  Google Scholar 

  16. Phaniendra A, Jestadi DB, Periyasamy L. Free radicals: properties, sources, targets and their implication in various diseases. Indian J Clin Biochem. 2015;30:11–26. https://doi.org/10.1007/s12291-014-0446-0.

    Article  CAS  PubMed  Google Scholar 

  17. Nunes-Silva A, Freitas-Lima L. The association between physical exercise and reactive oxygen species (ROS) production. J Sports Med Doping Stud. 2014;4:2161-0673.1000152. https://doi.org/10.4172/2161-0673.1000152.

    Article  Google Scholar 

  18. Buettner GR. Superoxide dismutase in redox biology: the roles of superoxide and hydrogen peroxide. Anti Cancer Agents Med Chem. 2011;11:341–6. https://doi.org/10.2174/187152011795677544.

    Article  CAS  Google Scholar 

  19. Droge W. Free radicals in the physiological control of cell function. Physiol Rev. 2002;82:47–95. https://doi.org/10.1152/physrev.00018.2001.

    Article  CAS  PubMed  Google Scholar 

  20. Kehrer JP, Robertson JD, Smith CV. Free radicals and reactive oxygen species. In: McQueen CA, editor. Comprehensive toxicology, vol. 1. 2nd ed. London: Elsevier Inc; 2010. p. 277–307.

    Chapter  Google Scholar 

  21. Fridovich I. Superoxide radical: an endogenous toxicant. Annu Rev Pharmacol Toxicol. 1983;23:239–57. https://doi.org/10.1146/annurev.pa.23.040183.001323.

    Article  CAS  PubMed  Google Scholar 

  22. Fridovich I. The biology of oxygen radicals. Science. 1978;201:875–80. https://doi.org/10.1126/science.210504.

    Article  CAS  PubMed  Google Scholar 

  23. Tchobanoglous G, Burton FL, Stensel HD. Wasterwater engineering: treatment and reuse. 4th ed. New York: Mc Graw Hill; 2003.

    Google Scholar 

  24. Munter R. Advanced oxidation processes: current status and prospects. Proc Estonian Acad Sci Chem. 2001;50:59–80.

    Article  CAS  Google Scholar 

  25. Underbakke ES, Surmeli NB, Smith BC, Wynia-Smith SL, Marletta MA. Nitric oxide signalling. In: Reedijk J, Poeppelmeier K, editors. Comprehensive inorganic chemistry ІІ: from elements to applications. 2nd ed. London: Elsevier Inc; 2013. p. 241–62. https://doi.org/10.1016/B978-0-08-097774-4.00320-X.

    Chapter  Google Scholar 

  26. Radi R. Oxygen radicals, nitric oxide and peroxynitrite: redox pathways in molecular medicine. Proc Natl Acad Sci U S A. 2018;115:5839–48. https://doi.org/10.1073/pnas.1804932115.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Bruckdorfer R. The basics about nitric oxide. Mol Asp Med. 2005;26:3–31. https://doi.org/10.1016/j.mam.2004.09.002.

    Article  CAS  Google Scholar 

  28. Genestra M. Oxyl radicals, redox-sensitive signalling cascades and antioxidants. Cell Signal. 2007;19:1807–19. https://doi.org/10.1016/j.cellsig.2007.04.009.

    Article  CAS  PubMed  Google Scholar 

  29. Wong H-S, Dighe PA, Mezera V, Monternier P-A, Brand MD. Production of superoxide and hydrogen peroxide from specific mitochondrial sites under different bioenergetic conditions. J Biol Chem. 2017;292:16804–9. https://doi.org/10.1074/jbc.R117.789271.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Giorgio M, Trinei M, Migliaccio E, Pelicci PG. Hydrogen peroxide: a metabolic by-product or a common mediator of ageing signals? Nat Rev Mol Cell Biol. 2007;8:722–8. https://doi.org/10.1038/nrm2240.

    Article  CAS  PubMed  Google Scholar 

  31. Dringen R, Pawlowski PG, Hirrlinger J. Peroxide detoxification by brain cells. J Neurosci Res. 2005;79:157–65. https://doi.org/10.1002/jnr.20280.

    Article  CAS  PubMed  Google Scholar 

  32. Halliwell B, Clement MV, Long LH. Hydrogen peroxide in the human body. FEBS Lett. 2000;486:10–3. https://doi.org/10.1016/s0014-5793(00)02197-9.

    Article  CAS  PubMed  Google Scholar 

  33. Armogida M, Nistico R, Mercury NB. Therapeutic potential of targeting hydrogen peroxide metabolism in the treatment of brain ischemia. Br J Pharmacol. 2012;166:1211–24. https://doi.org/10.1111/j.1476-5381.2012.01912.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Aldred EM, Buck C, Vall K. Free radicals. In: Pharmacology: A handbook for Complementary Healthcare Professionals. London: Elsevier Inc; 2009. p. 1–3.

    Google Scholar 

  35. Hrycay EG, Bandiera SM. Involvement of cytochrome P450 in reactive oxygen species formation and cancer. Adv Pharmacol. 2015;74:35–84. https://doi.org/10.1016/bs.apha.2015.03.003.

    Article  CAS  PubMed  Google Scholar 

  36. Manda G, Nechifor M, Neagu M. Reactive oxygen species, cancer and anti-cancer therapies. Curr Chem Biol. 2009;3:22–46.

    Article  Google Scholar 

  37. Stief TW. The physiology and pharmacology of singlet oxygen. Med Hypotheses. 2003;60:567–72. https://doi.org/10.1016/s0306-9877(03)00026-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Schoonbroodt S, Legrand-Poels S, Best-Belpomme M, Piette J. Activation of the NF-kappaB transcription factor in a T-lymphocytic cell line by hypochlorous acid. Biochem J. 1997;321:777–85. https://doi.org/10.1042/bj3210777.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Wentworth P Jr, McDunn JE, Wentworth AD, Takeuchi C, Nieva J, Jones T, Bautista C, Ruedi JM, Gutierrez A, Janda KD, Babior BM, Eschenmoser A, Lerner RA. Evidence for antibody-catalyzed ozone formation in bacterial killing and inflammation. Science. 2002;298:2195–9. https://doi.org/10.1126/science.1077642.

    Article  CAS  PubMed  Google Scholar 

  40. Zhu X, Wentworth P Jr, Wentworth AD, Eschenmoser A, Lerner RA, Wilson IA. Probing the antibody-catalyzed water-oxidation pathway at atomic resolution. Proc Natl Acad Sci U S A. 2004;101:2247–52. https://doi.org/10.1073/pnas.0307311101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Lerner RA, Eschenmoser A. Ozone in biology. Proc Natl Acad Sci U S A. 2003;100:3013–5. https://doi.org/10.1073/pnas.0730791100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Bocci V. Ozone as a bioregulator: pharmacology and toxicology of ozonetherapy today. J Biol Regul Homeost Agents. 1996;10:31–53.

    CAS  PubMed  Google Scholar 

  43. Agarwal A, Allamaneni SS. Role of free radicals in female reproductive diseases and assisted reproduction. Reprod Biomed Online. 2004;9:338–47. https://doi.org/10.1016/s1472-6483(10)62151-7.

    Article  CAS  PubMed  Google Scholar 

  44. Li W, Young JF, Sun J. NADPH oxidase-generated reactive oxygen species in mature follicles are essential for Drosophila ovulation. Proc Natl Acad Sci U S A. 2018;115:7765–70. https://doi.org/10.1073/pnas.1800115115.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Kampfer C, Saller S, Windschuttl S, Berg D, Berg U, Mayerhofer A. Pigment-epithelium derived factor (PEDF) and the human ovary: a role in the generation of ROS in granulosa cells. Life Sci. 2014;97:129–36. https://doi.org/10.1016/j.lfs.2013.12.007.

    Article  CAS  PubMed  Google Scholar 

  46. Fujii J, Iuchi Y, Okada F. Fundamental roles of reactive oxygen species and protective mechanisms in the female reproductive system. Reprod Biol Endocrinol. 2005;3:43. https://doi.org/10.1186/1477-7827-3-43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Agarwal A, Aponte-Mellado A, Premkumar BJ, Shaman A, Gupta S. The effects of oxidative stress on female reproduction: a review. Reprod Biol Endocrinol. 2012;10:49. https://doi.org/10.1186/1477-7827-10-49.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Ruder EH, Hartman TJ, Goldman MB. Impact of oxidative stress on female fertility. Curr Opin Obstet Gynecol. 2009;21:219. https://doi.org/10.1097/gco.0b013e32832924ba.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Behrman HR, Kodaman PH, Preston SL, Gao S. Oxidative stress and the ovary. J Soc Gynecol Investig. 2001;8:S40–2. https://doi.org/10.1016/s1071-5576(00)00106-4.

    Article  CAS  PubMed  Google Scholar 

  50. Freitas C, Neto AC, Matos L, Silva E, Ribeiro A, Silva-Carvalho J, Almeida H. Follicular fluid redox involvement for ovarian follicle growth. J Ovarian Res. 2017;10:44.

    Article  Google Scholar 

  51. Luddi A, Governini L, Capaldo A, Campanella G, De Leo V, Piomboni P, Morgante G. Characterization of the age-dependent changes in antioxidant defences and protein’s sulfhydryl/carbonyl stress in human follicular fluid. Antioxidants. 2020;9:927. https://doi.org/10.3390/antiox9100927.

    Article  CAS  PubMed Central  Google Scholar 

  52. Nelson SM, Telfer EE, Anderson RA. The ageing ovary and uterus: new biological insights. Hum Reprod Update. 2013;19:67–83. https://doi.org/10.1093/humupd/dms043.

    Article  CAS  PubMed  Google Scholar 

  53. Roselli M, Dubey RK, Imthurn B, Macas E, Keller PJ. Effects of nitric oxide on human spermatozoa: evidence that nitric oxide decreases sperm motility and induces sperm toxicity. Hum Reprod. 1995;10:1786–90. https://doi.org/10.1093/oxfordjournals.humrep.a136174.

    Article  Google Scholar 

  54. El Mouatassim S, Guerin P, Menezo Y. Expression of genes encoding antioxidant enzymes in human and mouse oocytes during the final stages of maturation. Mol Hum Reprod. 1999;5:720–5. https://doi.org/10.1093/molehr/5.8.720.

    Article  CAS  PubMed  Google Scholar 

  55. Ekerhovd E, Norstrom A. Involvement of a nitric oxide-cyclic guanosine monophosphate pathway in control of fallopian tube contractility. Gynecol Endocrinol. 2004;19:239–46. https://doi.org/10.1080/09513590400019296.

    Article  CAS  PubMed  Google Scholar 

  56. Al-Azemi M, Refaat B, Amer S, Ola B, Chapman N, Ledger W. The expression of inducible nitric oxide synthase in the human fallopian tube during the menstrual cycle and in ectopic pregnancy. Fertil Steril. 2010;94:833–40. https://doi.org/10.1016/j.fertnstert.2009.04.020.

    Article  CAS  PubMed  Google Scholar 

  57. Shao R, Zhang SX, Weijdegard B, Shein Z, Egecioglu E, Norstrom A, Brannstrom M, Billig H. Nitric oxide synthases and tubal ectopic pregnancies induced by Chlamydia infection: basic and clinical insights. Mol Hum Reprod. 2010;16:907–15.

    Article  CAS  Google Scholar 

  58. Griffith OW, Stuehr DJ. Nitric oxide synthases: properties and catalytic mechanisms. Annu Rev Physiol. 1995;57:707–36. https://doi.org/10.1146/annurev.ph.57.030195.003423.

    Article  CAS  PubMed  Google Scholar 

  59. Morris SM Jr, Billiar TR. New insights into the regulation of inducible nitric oxide synthesis. Am J Phys. 1994;266:E829–39. https://doi.org/10.1152/ajpendo.1994.266.6.E829.

    Article  CAS  Google Scholar 

  60. Tranguch S, Huet-Hudson Y. Decreased viability of nitric oxide synthase double knockout mice. Mol Reprod Dev. 2003;65:175–9. https://doi.org/10.1002/mrd.10274.

    Article  CAS  PubMed  Google Scholar 

  61. Zhan X, Li D, Johns RA. Expression of endothelial nitric oxide synthase in ciliated epithelia of rats. J Histochem Cytochem. 2003;51:81–7. https://doi.org/10.1177/002215540305100110.

    Article  CAS  PubMed  Google Scholar 

  62. Kalra A, Wehrle CJ, Tuma F. Anatomy, abdomen and pelvis, peritoneum. In: StatPearls. StatPearls Publishing; 2020.

    Google Scholar 

  63. Hoare BS, Khan YS. Anatomy, Abdomen and pelvis, female internal genitals. In: StatPearls. StatPearls Publishing; 2020.

    Google Scholar 

  64. Van Langerdonckt A, Casanas-Roux F, Donnez J. Oxidative stress and peritoneal endometriosis. Fertil Steril. 2002;77:861–70. https://doi.org/10.1016/s0015-0282(02)02959-x.

    Article  Google Scholar 

  65. Das S, Chattopadhyay R, Ghosh S, Ghosh S, Goswami SK, Chakravarty BN, Chaudhury K. Reactive oxygen species level in follicular fluid: embryo quality marker in IVF? Hum Reprod. 2006;21:2403–7. https://doi.org/10.1093/humrep/del156.

    Article  CAS  PubMed  Google Scholar 

  66. Donnez J, Binda MM, Donnez O, Dolmans M-M. Oxidative stress in the pelvic cavity and its role in the pathogenesis of endometriosis. Fertil Steril. 2016;106:1011–7. https://doi.org/10.1016/j.fertnstert.2016.07.1075.

    Article  CAS  PubMed  Google Scholar 

  67. Agarwal A, Durairajanayagam D, du Plessis SS. Utility of antioxidants during assisted reproductive techniques: an evidence-based review. Reprod Biol Endocrinol. 2014;12:112. https://doi.org/10.1186/1477-7827-12-112.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. DeCherney A, Hill MJ. The future of imaging and assisted reproduction. In: Rizk B, editor. Ultrasonography in reproductive medicine and infertility. Cambridge University Press; 2010. p. 1–10.

    Google Scholar 

  69. Rizk B, Badr M, Talerico C. Oxidative stress and the endometrium. In: Agarwal A, Aziz N, Rizk B, editors. Studies on women’s health. Springer; 2013. p. 61–74. https://doi.org/10.1007/978-1-62703-041-0_3.

    Chapter  Google Scholar 

  70. Ngo C, Chereaau C, Nicco C, Weill B, Chapron C, Batteux F. Reactive oxygen species controls endometriosis progression. Am J Pathol. 2009;175:225–34. https://doi.org/10.2353/ajpath.2009.080804.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Sikka SC. Relative impact of oxidative stress on male reproductive function. Curr Med Chem. 2001;8:851–62. https://doi.org/10.2174/0929867013373039.

    Article  CAS  PubMed  Google Scholar 

  72. Chen S-J, Allam J-P, Duan Y-G, Haidi G. Influence of reactive oxygen species on human sperm functions and fertilizing capacity including therapeutical approaches. Arch Gynecol Obstet. 2013;288:191–9. https://doi.org/10.1007/s00404-013-2801-4.

    Article  CAS  PubMed  Google Scholar 

  73. Haber F, Weiss J. Uber die katalyse des hydroperoxydes. Naturwissenschaften. 1932;20:948–50.

    Article  CAS  Google Scholar 

  74. Sen CK. Antioxidants and redox regulation of cellular signalling: introduction. Med Sci Sports Exerc. 2001;33:368–70. https://doi.org/10.1097/00005768-200103000-00005.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  76. Agarwal A, Virk G, Ong C, du Plessis SS. Effect of oxidative stress on male reproduction. World J Mens Health. 2014;32:1–17. https://doi.org/10.5534/wjmh.2014.32.1.1.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Sabeur K, Ball BA. Characterization of NADPH oxidase 5 in equine testis and spermatozoa. Reproduction. 2007;134:263–70. https://doi.org/10.1530/REP-06-0120.

    Article  CAS  PubMed  Google Scholar 

  78. Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol. 2003;552:335–44. https://doi.org/10.1113/jphysiol.2003.049478.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Attaran M, Pasqualotto E, Falcone T, Goldberg JM, Miller KF, Agarwal A, Sharma RK. The effect of follicular fluid reactive oxygen species on the outcome of in vitro fertilization. Int J Fertil Womens Med. 2000;45:314–20.

    CAS  PubMed  Google Scholar 

  80. Gharagozloo P, Aitken RJ. The role of sperm oxidative stress in male infertility and the significance of oral antioxidant therapy. Hum Reprod. 2011;26:1628–40. https://doi.org/10.1093/humrep/der132.

    Article  PubMed  Google Scholar 

  81. Agarwal A, Roychoudhury S, Bjugstad KB, Cho C-L. Oxidation-reduction potential of semen: what is its role in the treatment of male infertility? Ther Adv Urol. 2016;8:302–18. https://doi.org/10.1177/1756287216652779.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Saleh RA, Agarwal A, Nada EA, El-Tonsy MH, Sharma RK, Meyer A, Nelson DR, Thomas AJ. Negative effects of increased sperm DNA damages in relation to seminal oxidative stress in men with idiopathic and male factor infertility. Fertil Steril. 2003;79:1597–605. https://doi.org/10.1016/s0015-0282(03)00337-6.

    Article  PubMed  Google Scholar 

  83. Gil-Guzman E, Ollero M, Lopez MC, Shamra RK, Alvarez JG, Thomas AJ Jr, Agarwal A. Differential production of reactive oxygen species by subsets of human spermatozoa at different stages of maturation. Hum Reprod. 2001;16:1922–30. https://doi.org/10.1093/humrep/16.9.1922.

    Article  CAS  PubMed  Google Scholar 

  84. Agarwal A, Saleh RA, Bedaiwy MA. 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 

  85. Lavranos G, Balla M, Tzortzopoulou A, Syriou V, Angelopoulou R. Investigating ROS sources in male infertility: a common end for numerous pathways. Reprod Toxicol. 2012;34:298–307. https://doi.org/10.1016/j.reprotox.2012.06.007.

    Article  CAS  PubMed  Google Scholar 

  86. Shang Y, Liu C, Cui D, Han G, Yi S. The effect of chronic bacterial prostatitis on semen quality in adult men: a meta-analysis of case-control studies. Sci Rep. 2014;4:7233. https://doi.org/10.1038/srep07233.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Lu J-C, Huang Y-F, Lu N-Q. WHO laboratory manual for the examination and processing of human semen: its applicability to andrology laboratories in China. Zhonghua Nan Ke Xue. 2010;16:867–71.

    PubMed  Google Scholar 

  88. Rengan AK, Agarwal A, van der Linde M, du Plessis SS. An investigation of excess residual cytoplasm in human spermatozoa and its distinction from the cytoplasmic droplet. Reprod Biol Endocrinol. 2012;10:92. https://doi.org/10.1186/1477-7827-10-92.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Aziz N, Saleh RA, Sharma RK, Lewis-Jones I, Esfandiari N, Thomas AJ Jr, Agarwal A. Novel association between sperm reactive oxygen species production, sperm morphological defects and the sperm deformity index. Fertil Steril. 2004;81:349–54. https://doi.org/10.1016/j.fertnstert.2003.06.026.

    Article  CAS  PubMed  Google Scholar 

  90. Will MA, Swain J, Fode M, Sonksen J, Christman GM, Ohl D. The great debate: varicocele treatment and impact on fertility. Fertil Steril. 2011;95:841–52. https://doi.org/10.1016/j.fertnstert.2011.01.002.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Cho C-L, Esteves SC, Agarwal A. Novel insighst into the pathophysiology of varicocele and its association with reactive oxygen species and sperm DNA fragmentation. Asian J Androl. 2016;18:186–93. https://doi.org/10.4103/1008-682X.170441.

    Article  CAS  PubMed  Google Scholar 

  92. Shiraishi K, Matsuyama H, Takihara H. Pathophysiology of varicocele in male infertility in the era of assisted reproductive technology. Int J Urol. 2012;19:538–50. https://doi.org/10.1111/j.1442-2042.2012.02982.x.

    Article  CAS  PubMed  Google Scholar 

  93. Voglmayr JK, Setchell BP, White IG. The effects of heat on the metabolism and ultrastructure of ram testicular spermatozoa. J Reprod Fertil. 1971;24:71–80. https://doi.org/10.1530/jrf.0.0240071.

    Article  CAS  PubMed  Google Scholar 

  94. Morgan D, Cherny VV, Murphy R, Xu W, Thomas LL, DeCoursey TE. Temperature dependence of NADPH oxidase in human eosinophils. J Physiol. 2003;550:447–58. https://doi.org/10.1113/jphysiol.2003.041525.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Sakamoto Y, Ishikawa T, Kondo Y, Yamaguchi K, Fujisawa M. The assessment of oxidative stress in infertile patients with varicocele. BJU Int. 2008;101:1547–52. https://doi.org/10.1111/j.1464-410X.2008.07517.x.

    Article  CAS  PubMed  Google Scholar 

  96. Mostafa T, Anis T, Imam H, El-Nashar AR, Osman IA. Seminal reaxctive oxygen species-antioxidant relationship in fertile males with and without varicocele. Andrologia. 2009;41:125–9. https://doi.org/10.1111/j.1439-0272.2008.00900.x.

    Article  CAS  PubMed  Google Scholar 

  97. Monniaux D, Cadoret V, Clement F, Dalbies-Tran R, Elis S, Fabre S, Maillard V, Monget P, Uzbekova S. Folliculogenesis. In: Huhtaniemi I, Martini L, editors. Encyclopedia of endocrine diseases, vol. 2. 2nd ed; 2018. p. 377–98.

    Google Scholar 

  98. Tropea A, Miceli F, Minici F, Tiberi F, Orlando M, Gangale MF, Romani F, Catino S, Mancuso S, Navarra P, Lanzone A, Apa R. Regulation of vascular endothelial growth factor synthesis and release by human luteal cells in vitro. J Clin Endocrinol Metab. 2006;91:2303–9. https://doi.org/10.1210/jc.2005-2457.

    Article  CAS  PubMed  Google Scholar 

  99. Basini G, Grasselli F, Bianco F, Tirelli M, Tamanini C. Effects of reduced oxygen tension on reactive oxygen species production and activity of antioxidant enzymes in swine granulosa cells. Biofactors. 2004;20:61–9. https://doi.org/10.1002/biof.5520200201.

    Article  CAS  PubMed  Google Scholar 

  100. Laloraya M, Pradeep KG, Laloraya MM. Changes in the levels of superoxide anion radical and superoxide dismutase during the estrous cycle of Rattus norvegicus and induction of superoxide dismutase in rat ovary by lutropin. Biochem Biophys Res Commun. 1988;157:146–53. https://doi.org/10.1016/s0006-291x(88)80025-1.

    Article  CAS  PubMed  Google Scholar 

  101. Devine PJ, Perreault SD, Luderer U. Roles of reactive oxygen species and antioxidants in ovarian toxicity. Biol Reprod. 2012;86:27. https://doi.org/10.1095/biolreprod.111.095224.

    Article  CAS  PubMed  Google Scholar 

  102. Yu YS, Sui HS, Han ZB, Li W, Luo MJ, Tan JH. Apoptosis in granulosa cells during follicular atresia: relationship with steroids and insulin-like growth factors. Cell Res. 2004;14:341–6. https://doi.org/10.1038/sj.cr.7290234.

    Article  CAS  PubMed  Google Scholar 

  103. Kaipia A, Hsueh AJ. Regulation of ovarian follicle atresia. Annu Rev Physiol. 1997;59:349–63. https://doi.org/10.1146/annurev.physiol.59.1.349.

    Article  CAS  PubMed  Google Scholar 

  104. Sugino N. Reactive oxygen species in ovarian physiology. Reprod Med Biol. 2005;4:31–44. https://doi.org/10.1007/BF03016135.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Forman HJ, Torres M. Reactive oxygen species and cell signalling: respiratory burst in macrophage signalling. Am J Respir Crit Care Med. 2002;166:S4–8. https://doi.org/10.1164/rccm.2206007.

    Article  PubMed  Google Scholar 

  106. Rizzo A, Roscino MT, Binetti F, Sciorsci RL. Roles of reactive oxygen species in female reproduction. Reprod Domest Anim. 2012;47:344–52. https://doi.org/10.1111/j.1439-0531.2011.01891.x.

    Article  CAS  PubMed  Google Scholar 

  107. Ishikawa Y, Hirai K, Ogawa K. Cytochemical localization of hydrogen peroxide production in the rat uterus. J Histochem Cytochem. 1984;32:674–6. https://doi.org/10.1177/32.6.6725936.

    Article  CAS  PubMed  Google Scholar 

  108. Hemler ME, Cook HW, Lands WE. Prostaglandin biosynthesis can be triggered by lipid peroxidase. Arch Biochem Biophys. 1979;193:340–5. https://doi.org/10.1016/0003-9861(79)90038-9.

    Article  CAS  PubMed  Google Scholar 

  109. Morrow JD, Hill KE, Burk RF, Nammour TM, Badr KF, Roberts LJ 2nd. A series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism. Proc Natl Acad Sci U S A. 1990;87:9383–7. https://doi.org/10.1073/pnas.87.23.9383.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Riley JC, Behrman HR. Oxygen radicals and reactive oxygen species in reproduction. Proc Soc Exp Biol Med. 1991;198:781–91. https://doi.org/10.3181/00379727-198-43321c.

    Article  CAS  PubMed  Google Scholar 

  111. Russel DL, Robker RL. Molecular mechanism of ovulation: co-ordination through the cumulus complex. Hum Reprod Update. 2007;13:289–312. https://doi.org/10.1093/humupd/dml062.

    Article  Google Scholar 

  112. Richards JS, Russell DL, Ochsner S, Espey LL. Ovulation: new dimensions and new regulators of the inflammatory-like response. Annu Rev Physiol. 2002;64:69–92. https://doi.org/10.1146/annurev.physiol.64.081501.131029.

    Article  CAS  PubMed  Google Scholar 

  113. Shkolnik K, Tadmor A, Ben-Dor S, Nevo N, Galiani D, Dekel N. Reactive oxygen species are indispensable in ovulation. Proc Natl Acad Sci U S A. 2011;108:1462–7. https://doi.org/10.1073/pnas.1017213108.

    Article  PubMed  PubMed Central  Google Scholar 

  114. Brannstrom M, Mayrhofer G, Robertson SA. Localization of leukocyte subsets in the rat ovary during the pre-ovulatory period. Biol Reprod. 1993;48:277–86. https://doi.org/10.1095/biolreprod48.2.277.

    Article  CAS  PubMed  Google Scholar 

  115. Van der Hoek KH, Maddocks S, Woodhouse CM, van Rooijen N, Robertson SA, Norman RJ. Intrabursal injection of clodronate liposomes cause macrophage depletion and inhibits ovulation in the mouse ovary. Biol Reprod. 2000;62:1059–66. https://doi.org/10.1095/biolreprod62.4.1059.

    Article  PubMed  Google Scholar 

  116. DeYulia GJ Jr, Carcamo JM. EFG receptor-ligand interaction generates extracellular hydrogen peroxide that inhibits EGFR-associated protein tyrosine phosphatases. Biochem Biophys Res Commun. 2005;334:38–42. https://doi.org/10.1016/j.bbrc.2005.06.056.

    Article  CAS  PubMed  Google Scholar 

  117. Hsieh M, Lee D, Panigone S, Horner K, Chen R, Theologis A, Lee DC, Threadgill DW, Conti M. Luteinizing hormone-dependent activation of the epidermal growth factor network is essential for ovulation. Mol Cell Biol. 2007;27:1914–24. https://doi.org/10.1128/MCB.01919-06.

    Article  CAS  PubMed  Google Scholar 

  118. Miyazaki T, Sueoka K, Dharmarajan AM, Atlas SJ, Bulkley GB, Wallach EE. Effect of inhibition of oxygen free radical on ovulation and progesterone production by the in-vitro perfused rabbit ovary. J Reprod Fertil. 1991;91:207–12. https://doi.org/10.1530/jrf.0.0910207.

    Article  CAS  PubMed  Google Scholar 

  119. Chen L, Russell PT, Larsen WJ. Functional significance of cumulus expansion in the mouse: roles for the preovulatory synthesis of hyaluronic acid within the cumulus mass. Mol Reprod Dev. 1993;34:87–93. https://doi.org/10.1002/mrd.1080340114.

    Article  CAS  PubMed  Google Scholar 

  120. Kodaman PH, Behrman HR. Endocrine-regulated and protein kinase C-dependent generation of superoxide by rat preovulatory follicles. Endocrinology. 2001;142:687–93. https://doi.org/10.1210/endo.142.2.7961.

    Article  CAS  PubMed  Google Scholar 

  121. de Lamirande E, Gagnon C. Reactive oxygen species (ROS) and reproduction. In: Armstrong D, editor. Free radicals in diagnostic medicine. Springer; 1994. p. 185–97. https://doi.org/10.1007/978-1-4615-1833-4_14.

    Chapter  Google Scholar 

  122. Al-Gubory KH, Garrel C, Faure P, Sugino N. Roles of antioxidant enzymes in corpus luteum rescue from reactive oxygen species-induced oxidative stress. Reprod Biomed Online. 2012;25:551–60. https://doi.org/10.1016/j.rbmo.2012.08.004.

    Article  CAS  PubMed  Google Scholar 

  123. Sawada M, Carlson JC. Studies on the mechanism controlling generation of superoxide radical in luteinized rat ovaries during regression. Endocrinology. 1994;135:1645–50. https://doi.org/10.1210/endo.135.4.7925128.

    Article  CAS  PubMed  Google Scholar 

  124. Tanaka M, Miyazaki T, Tanigaki S, Kasai K, Minegishi K, Miyakoshi K, Ishimoto H, Yoshimura Y. Participation of reactive oxygen species in PGF2alpha-induced apoptosis in rat luteal cells. J Reprod Fertil. 2000;120:239–45. https://doi.org/10.1530/jrf.0.1200239.

    Article  CAS  PubMed  Google Scholar 

  125. Noda Y, Ota K, Shirasawa T, Shimizu T. Copper/zinc superoxide dismutase insufficiency impairs progesterone secretion and fertility in female mice. Biol Reprod. 2012;86:1–8. https://doi.org/10.1095/biolreprod.111.092999.

    Article  CAS  PubMed  Google Scholar 

  126. Shimamura K, Sugino N, Yoshida Y, Nakamura Y, Ogino K, Kato H. Changes in lipid peroxide and antioxidant enzyme activities in corpora lutea during pseudopregnancy in rats. J Reprod Fertil. 1995;105:253–7. https://doi.org/10.1530/jrf.0.1050253.

    Article  CAS  PubMed  Google Scholar 

  127. Sawada M, Carlson JC. Superoxide radical production in plasma membrane samples from regressing rat corpora lutea. Can J Physiol Pharmacol. 1989;67:465–71. https://doi.org/10.1139/y89-074.

    Article  CAS  PubMed  Google Scholar 

  128. Behrman HR, Preston SL. Luteolytic actions of peroxide in rat ovarian cells. Endocrinology. 1989;124:2895–900. https://doi.org/10.1210/endo-124-6-2895.

    Article  CAS  PubMed  Google Scholar 

  129. Behrman HR, Alten RF. Evidence that hydrogen peroxide blocks hormone-sensitive cholesterol transport into mitochondria of rat luteal cells. Endocrinology. 1991;128:2958–66. https://doi.org/10.1210/endo-128-6-2958.

    Article  CAS  PubMed  Google Scholar 

  130. Gagioti S, Colepicolo P, Bevilacqua E. Post-implantation mouse embryos have the capability to generate and release reactive oxygen species. Reprod Fertil Dev. 1995;7:1111–6. https://doi.org/10.1071/rd9951111.

    Article  CAS  PubMed  Google Scholar 

  131. Nasr-Esfahani MH, Winston NJ, Johnson MH. Effect of glucose, glutamine, ethylenediaminetetraacetic acid and oxygen tension on the concentration of reactive oxygen species and on development of the mouse preimplantation embryo in vitro. J Reprod Fertil. 1992;96:219–31. https://doi.org/10.1530/jrf.0.0960219.

    Article  CAS  PubMed  Google Scholar 

  132. Yamashita T, Yamazaki H, Kon Y, Watanabe T, Arikawa J, Miyoshi I, Kasai N, Kuwabara M. Progressive effect of alpha-phenyl-N-tert-butyl nitrone (PBN) on rat embryo development in vitro. Free Radic Biol Med. 1997;23:1073–7. https://doi.org/10.1016/s0891-5849(97)00139-1.

    Article  CAS  PubMed  Google Scholar 

  133. Guerin P, El Mouatassim S, Menezo Y. Oxidative stress and protection against reactive oxygen species in the pre-implantation embryo and its surroundings. Hum Reprod Update. 2001;7:175–89. https://doi.org/10.1093/humupd/7.2.175.

    Article  CAS  PubMed  Google Scholar 

  134. Mannaerts D, Faes E, Cos P, Briede JJ, Gyselaers W, Cornette J, Gorbanev Y, Bogaerts A, Spaanderman M, Van Craenenbroek E, Jacquemyn Y. Oxidative stress in healthy pregnancy and preeclampsia in linked to chronic inflammation, iron status and vascular function. PLoS One. 2018;13:e0202919. https://doi.org/10.1371/journal.pone.0202919.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Myatt L, Cui X. Oxidative stress in the placenta. Histochem Cell Biol. 2004;122:369–82. https://doi.org/10.1007/s00418-004-0677-x.

    Article  CAS  PubMed  Google Scholar 

  136. Abrahams VM, Kim YM, Straszewski SL, Romero R, Mor G. Macrophage and apoptotic cell clearance during pregnancy. Am J Reprod Immunol. 2004;51:275–82. https://doi.org/10.1111/j.1600-0897.2004.00156.x.

    Article  PubMed  Google Scholar 

  137. Khalil A, Jauniaux E, Cooper D, Harrington K. Pulse wave analysis in normal pregnancy: a prospective longitudinal study. PLoS One. 2009;4:e6134. https://doi.org/10.1371/journal.pone.0006134.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Wu F, Tian F-J, Lin Y, Xu W-M. Oxidative stress: placenta function and dysfunction. Am J Reprod Immunol. 2016;76:258–71. https://doi.org/10.1111/aji.12454.

    Article  PubMed  Google Scholar 

  139. Krause BJ, Hanson MA, Casanello P. Role of nitric oxide in placental vascular development and function. Placenta. 2011;32:797–805. https://doi.org/10.1016/j.placenta.2011.06.025.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Wu F, Tian F-J, Lin Y. Oxidative stress in placenta: health and diseases. Biomed Res Int. 2015;2015:293271. https://doi.org/10.1155/2015/293271.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Liu A-X, Jin F, Zhang W-W, Zhou T-H, Zhou C-Y, Yao W-M, Qian Y-L, Huang H-F. Proteomic analysis on the alteration of protein expression in the placental villous tissue of early pregnancy loss. Biol Reprod. 2006;75:414–20. https://doi.org/10.1095/biolreprod.105.049379.

    Article  CAS  PubMed  Google Scholar 

  142. Conner EM, Grisham MB. Inflammation, free radicals and antioxidants. Nutrition. 1996;12:274–7. https://doi.org/10.1016/s0899-9007(96)00000-8.

    Article  CAS  PubMed  Google Scholar 

  143. Jenkin G, Young IR. Mechanism responsible for parturition: the use of experimental models. Anim Reprod Sci. 2004;82–83:567–81. https://doi.org/10.1016/j.anireprosci.2004.05.010.

    Article  CAS  PubMed  Google Scholar 

  144. Golightly E, Jabbour HN, Norman JE. Endocrine immune interactions in human parturition. Mol Cell Endocrinol. 2011;335:52–9. https://doi.org/10.1016/j.mce.2010.08.005.

    Article  CAS  PubMed  Google Scholar 

  145. Masumoto N, Tasaka K, Miyake A, Tanizawa O. Superoxide anion increases intracellular free calcium in human myometrial cells. J Biol Chem. 1990;265:22533–6.

    Article  CAS  Google Scholar 

  146. Appiah I, Milovanovic S, Radojicic R, Nikolic-Kokic A, Orescanin-Dusic Z, Slavic M, Trbojevic S, Skrbic R, Spasic M, Blagojevic D. Hydrogen peroxide affects contractile activity and antioxidant enzymes in rat uterus. Br J Pharmacol. 2009;158:1932–41. https://doi.org/10.1111/j.1476-5381.2009.00490.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. O’Donovan DJ, Fernandes CJ. Free radicals and diseases in premature infants. Antioxid Redox Signal. 2004;6:169–76. https://doi.org/10.1089/152308604771978471.

    Article  CAS  PubMed  Google Scholar 

  148. Kovalski N, de Lamirande E, Gagnon C. Reactive oxygen species generated by human neutrophils inhibit sperm motility: protective effect of seminal plasma and scavengers. Fertil Steril. 1992;58:809–16. https://doi.org/10.1016/S0015-0282(16)55332-1.

    Article  CAS  PubMed  Google Scholar 

  149. Guerriero G, Trocchia S, Abdel-Gawad FK, Ciarcia G. Roles of reactive oxygen species in the spermatogenesis regulation. Front Endocrinol (Lausanne). 2014;5:56. https://doi.org/10.3389/fendo.2014.00056.

    Article  Google Scholar 

  150. Shi Y, Buffenstein R, Pulliam DA, Van Remmen H. Comparative study of oxidative stress and mitochondrial function in aging. Integr Comp Biol. 2010;50:869–79. https://doi.org/10.1093/icb/icq079.

    Article  PubMed  Google Scholar 

  151. Fujii J, Imai H. Redox reactions in mammalian spermatogenesis and the potential targets of reactive oxygen species under oxidative stress. Spermatogenesis. 2014;4:e979108. https://doi.org/10.4161/21565562.2014.979108.

    Article  PubMed  PubMed Central  Google Scholar 

  152. Lui W-Y, Cheng CY. Transcription regulation in spermatogenesis. Adv Exp Med Biol. 2008;636:115–32. https://doi.org/10.1007/978-0-387-09597-4_7.

    Article  CAS  PubMed  Google Scholar 

  153. Chen C, Ouyang W, Grigura V, Zhou Q, Carnes K, Lim H, Zhao G-Q, Arber S, Kurpios N, Murphy TL, Cheng AM, Hassell JA, Chandrashekar V, Hofmann M-C, Hess RA, Murphy KM. ERM is required for transcriptional control of the spermatogonial stem cell niche. Nature. 2005;436:1030–4. https://doi.org/10.1038/nature03894.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Grimes SR. Testis-specific transcriptional control. Gene. 2004;343:11–22. https://doi.org/10.1016/j.gene.2004.08.021.

    Article  CAS  PubMed  Google Scholar 

  155. Aitken RJ, Roman SD. Antioxidant system and oxidative stress in the stress. Oxidative Med Cell Longev. 2008;1:15–24. https://doi.org/10.4161/oxim.1.1.6843.

    Article  Google Scholar 

  156. Montano MM, Deng H, Liu M, Sun X, Singal R. Transcriptional regulation by the estrogen receptor of antioxidative stress enzymes and its functional implications. Oncogene. 2004;23:2442–53. https://doi.org/10.1038/sj.onc.1207358.

    Article  CAS  PubMed  Google Scholar 

  157. Aitken RJ, Gordon E, Harkiss D, Twigg JP, Milne P, Jennings Z, Irvine DS. Relative impact of oxidative stress on the functional competence and genomic integrity of human spermatozoa. Biol Reprod. 1998;59:1037–46. https://doi.org/10.1095/biolreprod59.5.1037.

    Article  CAS  PubMed  Google Scholar 

  158. Saowaros W, Panyim S. The formation of disulphide bonds in human protamines during sperm maturation. Experientia. 1979;35:191–2. https://doi.org/10.1007/BF01920608.

    Article  CAS  PubMed  Google Scholar 

  159. Cheng W-M, An L, Wu Z-H, Zhu Y-B, Liu J-H, Gao H-M, Li X-H, Zheng S-J, Chen D-B, Tian J-H. Effects of disulphide bond reducing agents on sperm chromatin structural integrity and developmental competence of in vitro matured oocytes after intracytoplasmic sperm injection in pigs. Reproduction. 2009;137:633–43. https://doi.org/10.1530/REP-08-0143.

    Article  CAS  PubMed  Google Scholar 

  160. Hutchinson JM, Rau DC, DeRouchey JE. Role of disulphide bonds on DNA packaging forces in bull sperm chromatin. Biophys J. 2017;113:1925–33. https://doi.org/10.1016/j.bpj.2017.08.050.

    Article  CAS  Google Scholar 

  161. Rousseaux J, Rousseaux-Prevost R. Molecular localization of free thiols in human sperm chromatin. Biol Reprod. 1995;52:1066–72. https://doi.org/10.1095/biolreprod52.5.1066.

    Article  CAS  PubMed  Google Scholar 

  162. Roveri A, Ursini F, Flohe L, Maiorino M. PHGPx and spermatogenesis. Biofactors. 2001;14:213–22. https://doi.org/10.1002/biof.5520140127.

    Article  CAS  PubMed  Google Scholar 

  163. Eisenbach M. Mammalian sperm chemotaxis and its association with capacitation. Dev Genet. 1999;25:87–94. https://doi.org/10.1002/(SICI)1520-6408(1999)25:2<87::AID-DVG2>3.0.CO;2-4.

    Article  CAS  PubMed  Google Scholar 

  164. Aitken RJ. Reactive oxygen species as mediators of sperm capacitation and pathological damage. Mol Reprod Dev. 2017;84:1039–52. https://doi.org/10.1002/mrd.22871.

    Article  CAS  PubMed  Google Scholar 

  165. Gualtieri R, Mollo V, Duma G, Talevi R. Redox control of surface protein sulphhydryls in bovine spermatozoa reversibly modulates sperm adhesion to the oviductal epithelium and capacitation. Reproduction. 2009;138:33–43. https://doi.org/10.1530/REP-08-0514.

    Article  CAS  PubMed  Google Scholar 

  166. O’Flaherty C. Redox regulation of mammalian sperm capacitation. Asian J Urol. 2015;17:583–90. https://doi.org/10.4103/1008-682X.153303.

    Article  CAS  Google Scholar 

  167. Kralikova M, Crha I, Huser M, Melounova J, Zakova J, Matejovicova M, Ventruba P. The intracellular concentration of homocysteine and related thiols is negatively correlated to sperm quality after highly effective method of sperm lysis. Andrologia. 2017;49:e12702. https://doi.org/10.1111/and.12702.

    Article  CAS  Google Scholar 

  168. de Lamirande E, Harakat A, Gagnon C. 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. 1998;19:215–25. https://doi.org/10.1002/j.1939-4640.1998.tb01991.x.

    Article  PubMed  Google Scholar 

  169. Suarez SS. Control of hyperactivation in sperm. Hum Reprod Update. 2008;14:647–57. https://doi.org/10.1093/humupd/dmn029.

    Article  CAS  PubMed  Google Scholar 

  170. de Lamirande E, Jiang H, Zini A, Kodama H, Gagnon C. Reactive oxygen species and sperm physiology. Rev Reprod. 1997;2:48–54. https://doi.org/10.1530/ror.0.0020048.

    Article  PubMed  Google Scholar 

  171. Zini A, de Lamirande E, Gagnon C. Low levels of nitric oxide promote human sperm capacitation in vitro. J Androl. 1995;16:424–31. https://doi.org/10.1002/j.1939-4640.1995.tb00558.x.

    Article  CAS  PubMed  Google Scholar 

  172. de Lamirande E, Lamothe G. Reactive oxygen-induces reactive oxygen formation during human sperm capacitation. Free Radic Biol Med. 2009;46:502–10. https://doi.org/10.1016/j.freeradbiomed.2008.11.004.

    Article  CAS  PubMed  Google Scholar 

  173. du Plessis SS, Agarwal A, Halabi J, Tvrda E. Contemporary evidence on the physiological role of reactive oxygen species in human sperm function. J Assist Reprod Genet. 2015;32:509–20. https://doi.org/10.1007/s10815-014-0425-7.

    Article  PubMed  PubMed Central  Google Scholar 

  174. Breitbart H, Spungin B. The biochemistry of the acrosome reaction. Mol Hum Reprod. 1997;3:195–202. https://doi.org/10.1093/molehr/3.3.195.

    Article  CAS  PubMed  Google Scholar 

  175. Breitbart H, Naor Z. Protein kinase in mammalian sperm capacitation and the acrosome reaction. Rev Reprod. 1999;4:151–9. https://doi.org/10.1530/ror.0.0040151.

    Article  CAS  PubMed  Google Scholar 

  176. Ichikawa T, Oeda T, Ohmori H, Schill WB. Reactive oxygen species influence the acrosome reaction but not acrosin activity in human spermatozoa. Int J Androl. 1999;22:37–42. https://doi.org/10.1046/j.1365-2605.1999.00145.x.

    Article  CAS  PubMed  Google Scholar 

  177. de Lamirande E, Gagnon C. A positive role for the superoxide anion in triggering hyperactivation and capacitation of human spermatozoa. Int J Androl. 1993;16:21–5. https://doi.org/10.1111/j.1365-2605.1993.tb01148.x.

    Article  PubMed  Google Scholar 

  178. Boerke A, Tsai PS, Garcia-Gill N, Brewis IA, Gadella BM. Capacitation-dependent reorganization of microdomains in the apical sperm head plasma membrane: functional relationship with zona binding and the zona-induced acrosome reaction. Theriogenology. 2008;70:1188–96. https://doi.org/10.1016/j.theriogenology.2008.06.021.

    Article  CAS  PubMed  Google Scholar 

  179. de Lamirande E, Tsai C, Harakat A, Gagnon C. Involvement of reactive oxygen species in human sperm acrosome reaction induced by A23187, lysophosphatidylcholine and biological fluid ultrafiltrates. J Androl. 1998;19:585–94. https://doi.org/10.1002/j.1939-4640.1998.tb02061.x.

    Article  PubMed  Google Scholar 

  180. Herrero MB, de Lamirande E, Gagnon C. Nitric oxide is a signalling molecule in spermatozoa. Curr Pharm Des. 2003;9:419–25. https://doi.org/10.2174/1381612033391720.

    Article  CAS  PubMed  Google Scholar 

  181. Aitken RJ, Paterson M, Fisher H, Buckingham DW, van Duin M. Redox regulation of tyrosine phosphorylation in human spermatozoa and its role in the control of human sperm function. J Cell Sci. 1995;108:2017–25. https://doi.org/10.1242/jcs.108.5.2017.

    Article  CAS  PubMed  Google Scholar 

  182. Griveau JF, Renard P, Le Lannou D. Superoxide anion production by human spermatozoa as a part of the ionophore-induced acrosome reaction process. Int J Androl. 1995;18:67–74. https://doi.org/10.1111/j.1365-2605.1995.tb00388.x.

    Article  CAS  PubMed  Google Scholar 

  183. Aitken RJ, Buckingham DW, Harkiss D, Paterson M, Fisher H, Irvine DS. The extragenomic action of progesterone on human spermatozoa is influenced by redox regulated changes in tyrosine phosphorylation during capacitation. Mol Cell Endocrinol. 1996;117:83–93. https://doi.org/10.1016/0303-7207(95)03733-0.

    Article  CAS  PubMed  Google Scholar 

  184. Aitken RJ, Buckingham DW, West KM. Reactive oxygen species and human spermatozoa: analysis of the cellular mechanism involved in luminol- and lucigenin-dependent chemiluminescence. J Cell Physiol. 1992;151:466–77. https://doi.org/10.1002/jcp.1041510305.

    Article  CAS  PubMed  Google Scholar 

  185. Ohzu E, Yanagimachi R. Acceleration of acrosome reaction in hamster spermatozoa by lysolecithin. J Exp Zool. 1982;224:259–63. https://doi.org/10.1002/jez.1402240216.

    Article  CAS  PubMed  Google Scholar 

  186. Goldman R, Ferber E, Zort U. Reactive oxygen species are involved in the activation of cellular phospholipase A2. FEBS Lett. 1992;309:190–2. https://doi.org/10.1016/0014-5793(92)81092-z.

    Article  CAS  PubMed  Google Scholar 

  187. Zor U, Ferber E, Gergely P, Szucs K, Dombradi V, Goldman R. Reactive oxygen species mediate phorbol ester-regulated tyrosine phosphorylation and phospholipase A2 activation: potentiation by vanadate. Biochem J. 1993;295:879–88. https://doi.org/10.1042/bj2950879.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Aitken RJ. Molecular mechanisms regulating human sperm function. Mol Hum Reprod. 1997;3:169–73. https://doi.org/10.1093/molehr/3.3.169.

    Article  CAS  PubMed  Google Scholar 

  189. Sanchez R, Sepulveda C, Risopatron J, Villegas J, Giojalas LC. Human sperm chemotaxis depends on critical levels of reactive oxygen species. Fertil Steril. 2010;93:150–3. https://doi.org/10.1016/j.fertnstert.2008.09.049.

    Article  CAS  PubMed  Google Scholar 

  190. Sharma R, Roychoudhury S, Alsaad R, Bamajbuor F. Negative effects of oxidative stress (OS) on reproductive system at cellular level. In: Agarwal A, Sharma RK, Gupta S, Harlev A, Ahmad G, du Plessis SS, Esteves SC, Wang SM, Durairajanayagam D, editors. Oxidative stress in human reproduction shedding light on a complicated phenomenon. Springer; 2017. p. 65–88. https://doi.org/10.1007/978-3-319-48427-3_4.

    Chapter  Google Scholar 

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Authors and Affiliations

  1. Department of Life Science and Bioinformatics, Assam University, Silchar, India

    Anandan Das & Shubhadeep Roychoudhury

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  1. Anandan Das
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  2. Shubhadeep Roychoudhury
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  1. Department of Bioproducts and Biosystems, School of Chemical Engineering, Aalto University, Espoo, Finland

    Kavindra Kumar Kesari

  2. Department of Life Science and Bioinformatics, Assam University, Silchar, India

    Shubhadeep Roychoudhury

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Das, A., Roychoudhury, S. (2022). Reactive Oxygen Species in the Reproductive System: Sources and Physiological Roles. In: Kesari, K.K., Roychoudhury, S. (eds) Oxidative Stress and Toxicity in Reproductive Biology and Medicine. Advances in Experimental Medicine and Biology, vol 1358. Springer, Cham. https://doi.org/10.1007/978-3-030-89340-8_2

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