Advertisement

New Insights into Sperm Physiology and Pathology

  • R. John Aitken
  • Mark A. Baker
  • Geoffry N. De Iuliis
  • Brett Nixon
Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 198)

Abstract

Infertility is a relatively common condition affecting approximately one in ten of the population. In half of these cases, a male factor is involved, making defective sperm function the largest single, defined cause of human infertility. Among other factors, recent data suggest that oxidative stress plays a major role in the etiology of this condition. Spermatozoa spontaneously produce a variety of reactive oxygen species (ROS) including the superoxide anion, hydrogen peroxide and nitric oxide. Produced in small amounts, ROS are functionally important in driving the tyrosine phosphorylation cascades associated with sperm capacitation. However, when ROS production exceeds the spermatozoa’s limited antioxidant defenses, a state of oxidative stress is induced characterized by peroxidative damage to the sperm plasma membrane and DNA strand breakage in the sperm nucleus. Such oxidative stress not only disrupts the fertilizing potential of human spermatozoa but also the ability of these cells to create a normal healthy embryo. As a result, DNA damage in human spermatozoa is correlated with an increased incidence of miscarriage and various kinds of morbidity in the offspring. These insights into the pathophysiology of defective sperm function have clear implications for the diagnosis and treatment of male infertility, particularly with respect to the potential importance of antioxidant therapy. These concepts may also be relevant to the design of novel approaches to male contraception that attempt to replicate the pathological situation.

Keywords

Chromatin protamination Oxidative stress Reactive oxygen species DNA damage Spermatozoa 

Abbreviations

8OHdG

8-OH, 2′-deoxyguanosine

cAMP

Cyclic adenosine monophosphate

CMA3

Chromomycin

DPI

Diphenylene iodonium

DUOX

Dual oxidase

H2O2

Hydrogen peroxide

NAD(P)H

Nicotinamide adenine dinucleotide phosphate

NO

Nitric oxide

NOX

NAD(P)H oxidase family

ONOO

Peroxynitrite

PKA

Protein kinase A

ROS

Reactive oxygen species

SOD

Superoxide dismutase

References

  1. Agarwal A, Makker K, Sharma R (2008) Clinical relevance of oxidative stress in male factor infertility: an update. Am J Reprod Immunol 59:2–11PubMedGoogle Scholar
  2. Aitken RJ (2004) Founders’ Lecture. Human spermatozoa: fruits of creation, seeds of doubt. Reprod Fertil Dev 16:655–664PubMedGoogle Scholar
  3. Aitken RJ, Baker HW (1995) Seminal leukocytes: passengers, terrorists or good samaritans? Hum Reprod 10:1736–1739PubMedGoogle Scholar
  4. Aitken RJ, Baker MA (2006) Oxidative stress, sperm survival and fertility control. Mol Cell Endocrinol 250:66–69PubMedGoogle Scholar
  5. Aitken RJ, Clarkson JS (1987) Cellular basis of defective sperm function and its association with the genesis of reactive oxygen species by human spermatozoa. J Reprod Fertil 81:459–469PubMedGoogle Scholar
  6. Aitken RJ, Clarkson JS (1988) Significance of reactive oxygen species and anti-oxidants in defining the efficacy of sperm preparation techniques. J Androl 9:367–376PubMedGoogle Scholar
  7. Aitken RJ, Fisher H (1994) Reactive oxygen species generation and human spermatozoa: the balance of benefit and risk. Bioessays 16:259–267PubMedGoogle Scholar
  8. Aitken RJ, Krausz CG (2001) Oxidative stress, DNA damage and the Y chromosome. Reproduction 122:497–506PubMedGoogle Scholar
  9. Aitken RJ, Marshall Graves JA (2002) The future of sex. Nature 415:963PubMedGoogle Scholar
  10. Aitken RJ, Clarkson JS, Fishel S (1989a) Generation of reactive oxygen species, lipid peroxidation and human sperm function. Biol Reprod 41:183–187PubMedGoogle Scholar
  11. Aitken RJ, Clarkson JS, Hargreave TB, Irvine DS, Wu FCW (1989b) Analysis of the relationship between defective sperm function and the generation of reactive oxygen species in cases of oligozoospermia. J Androl 10:214–220PubMedGoogle Scholar
  12. Aitken RJ, Irvine DS, Wu FC (1991) Prospective analysis of sperm-oocyte fusion and reactive oxygen species generation as criteria for the diagnosis of infertility. Am J Obstet Gynec 164:542–551PubMedGoogle Scholar
  13. Aitken RJ, Harkiss D, Buckingham D (1993a) Relationship between iron-catalysed lipid peroxidation potential and human sperm function. J Reprod Fert 98:257–265Google Scholar
  14. Aitken RJ, Harkiss D, Buckingham DW (1993b) Analysis of lipid peroxidation mechanisms in human spermatozoa. Molec Reprod Devel 35:302–315Google Scholar
  15. Aitken RJ, Paterson M, Fisher H, Buckingham DW, van Duin M (1995) Redox regulation of tyrosine phosphorylation in human spermatozoa and its role in the control of human sperm function. J Cell Sci 108:2017–2025PubMedGoogle Scholar
  16. 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 21:495–504PubMedGoogle Scholar
  17. Aitken RJ, Fisher HM, Fulton N, Gomez E, Knox W, Lewis B, Irvine S (1997) Reactive oxygen species generation by human spermatozoa is induced by exogenous NADPH and inhibited by the flavoprotein inhibitors diphenylene iodonium and quinacrine. Mol Reprod Dev 47:468–482PubMedGoogle Scholar
  18. Aitken RJ, Gordon E, Harkiss D, Twigg JP, Milne P, Jennings Z, Irvine DS (1998a) Relative impact of oxidative stress on the functional competence and genomic integrity of human spermatozoa. Biol Reprod 59:1037–1046PubMedGoogle Scholar
  19. Aitken RJ, Harkiss D, Knox W, Paterson M, Irvine DS (1998b) A novel signal transduction cascade in capacitating human spermatozoa characterised by a redox-regulated, cAMP-mediated induction of tyrosine phosphorylation. J Cell Sci 111:645–656PubMedGoogle Scholar
  20. Aitken RJ, Ryan AL, Curry BJ, Baker MA (2003) Multiple forms of redox activity in populations of human spermatozoa. Mol Hum Reprod 9:645–661PubMedGoogle Scholar
  21. Aitken RJ, Baker MA, O’Bryan M' (2004a) Shedding light on chemiluminescence: the application of chemiluminescence in diagnostic andrology. J Androl 25:455–465PubMedGoogle Scholar
  22. Aitken RJ, Ryan AL, Baker MA, McLaughlin EA (2004b) Redox activity associated with the maturation and capacitation of mammalian spermatozoa. Free Radic Biol Med 36:994–1010PubMedGoogle Scholar
  23. Aitken RJ, Bennetts LE, Sawyer D, Wiklendt AM, King BV (2005) Impact of radio frequency electromagnetic radiation on DNA integrity in the male germline. Int J Androl 28:171–179PubMedGoogle Scholar
  24. Aitken RJ, Wingate JK, De Iuliis GN, Koppers AJ, McLaughlin EA (2006) Cis-unsaturated fatty acids stimulate reactive oxygen species generation and lipid peroxidation in human spermatozoa. J Clin Endocrinol Metab 91:4154–4163PubMedGoogle Scholar
  25. Aitken RJ, Nixon B, Lin M, Koppers AJ, Lee YH, Baker MA (2007) Proteomic changes in mammalian spermatozoa during epididymal maturation. Asian J Androl 9:554–564PubMedGoogle Scholar
  26. Aitken RJ, Baker MA, Doncel GF, Matzuk MM, Mauck CK, Harper MJ (2008) As the world grows: contraception in the 21st century. J Clin Invest 118:1330–1343PubMedGoogle Scholar
  27. Aitken RJ, De Iuliis GN, McLachlan RI (2009) Biological and clinical significance of DNA damage in the male germ line. Int J Androl 32:46–56PubMedGoogle Scholar
  28. Aleem M, Padwal V, Choudhari J, Balasinor N, Gill-Sharma MK (2008) Sperm protamine levels as indicators of fertilising potential in sexually mature male rats. Andrologia 40:29–37PubMedGoogle Scholar
  29. Alvarez JG, Touchstone JC, Blasco L, Storey BT (1987) Spontaneous lipid peroxidation and production of hydrogen peroxide and superoxide in human spermatozoa. J Androl 8:338–348PubMedGoogle Scholar
  30. Austin CR (1951) Observations on the penetration of the sperm into the mammalian egg. Aust J Sci Res B 4:581–596PubMedGoogle Scholar
  31. Badouard C, Ménézo Y, Panteix G, Ravanat JL, Douki T, Cadet J, Favier A (2008) Determination of new types of DNA lesions in human sperm. Zygote 16:9–13PubMedGoogle Scholar
  32. Baker MA, Krutskikh A, Curry BJ, McLaughlin EA, Aitken RJ (2004) Identification of cytochrome P450-reductase as the enzyme responsible for NADPH-dependent lucigenin and tetrazolium salt reduction in rat epididymal sperm preparations. Biol Reprod 71:307–318PubMedGoogle Scholar
  33. Baker MA, Krutskikh A, Curry BJ, Hetherington L, Aitken RJ (2005) Identification of cytochrome-b5 reductase as the enzyme responsible for NADH-dependent lucigenin chemiluminescence in human spermatozoa. Biol Reprod 73:334–342PubMedGoogle Scholar
  34. Baker MA, Hetherington L, Aitken RJ (2006) Identification of SRC as a key PKA-stimulated tyrosine kinase involved in the capacitation-associated hyperactivation of murine spermatozoa. J Cell Sci 119:3182–3192PubMedGoogle Scholar
  35. Baker MA, Reeves G, Hetherington L, Müller J, Baur I, Aitken RJ (2007) Identification of gene products present in Triton X-100 soluble and insoluble fractions of human spermatozoa lysates using LC-MS/MS analysis. Proteomics Clin Appl 1:524–532PubMedGoogle Scholar
  36. Ball BA (2008) Oxidative stress, osmotic stress and apoptosis: impacts on sperm function and preservation in the horse. Anim Reprod Sci 107:257–267PubMedGoogle Scholar
  37. Banfi B, Molnar G, Maturana A, Steger K, Hegedus B, Demaurex N, Krause KH (2001) A Ca(2+)-activated NADPH oxidase in testis, spleen, and lymph nodes. J Biol Chem 276:37594–37601PubMedGoogle Scholar
  38. Baumber J, Ball BA, Linfor JJ, Meyers SA (2003) Reactive oxygen species and cryopreservation promote DNA fragmentation in equine spermatozoa. J Androl 24:621–628PubMedGoogle Scholar
  39. Bennetts LE, Aitken RJ (2005) A comparative study of oxidative DNA damage in mammalian spermatozoa. Molec Reprod Dev 71:77–87PubMedGoogle Scholar
  40. Bennetts LE, De Iuliis GN, Nixon B, Kime M, Zelski K, McVicar CM, Lewis SE, Aitken RJ (2008) Impact of estrogenic compounds on DNA integrity in human spermatozoa: evidence for cross-linking and redox cycling activities. Mutat Res 641:1–11PubMedGoogle Scholar
  41. Bize I, Santander G, Cabello P, Driscoll D, Sharpe C (1991) Hydrogen peroxide is involved in hamster sperm capacitation in vitro. Biol Reprod 44:398–403PubMedGoogle Scholar
  42. Burnaugh L, Sabeur K, Ball BA (2007) Generation of superoxide anion by equine spermatozoa as detected by dihydroethidium. Theriogenology 67:580–589PubMedGoogle Scholar
  43. Chang MC (1951) Fertilizing capacity of spermatozoa deposited into the Fallopian tubes. Nature 168:697–698PubMedGoogle Scholar
  44. Codrington AM, Hales BF, Robaire B (2007) Exposure of male rats to cyclophosphamide alters the chromatin structure and basic proteome in spermatozoa. Hum Reprod 22:1431–1442PubMedGoogle Scholar
  45. De Iuliis GN, Wingate JK, Koppers AJ, McLaughlin EA, Aitken RJ (2006) Definitive evidence for the nonmitochondrial production of superoxide anion by human spermatozoa. J Clin Endocrinol Metab 91:1968–1975PubMedGoogle Scholar
  46. De Iuliis GN, Newey RJ, King BV, Aitken RJ (2009) Mobile phone radiation induces reactive oxygen species production and DNA damage in human spermatozoa in vitro. PLoS ONE 4(7):e6446PubMedGoogle Scholar
  47. de Lamirande E, Gagnon C (1993) Human sperm hyperactivation and capacitation as parts of an oxidative process. Free Radic Biol Med 14:157–166PubMedGoogle Scholar
  48. de Lamirande E, Gagnon C (1995) Capacitation-associated production of superoxide anion by human spermatozoa. Free Radic Biol Med 18:487–496PubMedGoogle Scholar
  49. de Lamirande E, O’Flaherty C (2008) Sperm activation: role of reactive oxygen species and kinases. Biochim Biophys Acta 1784:106–115PubMedGoogle Scholar
  50. de Lamirande E, Leclerc P, Gagnon C (1997) Capacitation as a regulatory event that primes spermatozoa for the acrosome reaction and fertilization. Mol Hum Reprod 3:175–194PubMedGoogle Scholar
  51. de Lamirande E, Harakat A, 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 19:215–225PubMedGoogle Scholar
  52. Deepinder F, Makker K, Agarwal A (2007) Cell phones and male infertility: dissecting the relationship. Reprod Biomed Online 15:266–270PubMedGoogle Scholar
  53. Ecroyd H, Jones RC, Aitken RJ (2003) Endogenous redox activity in mouse spermatozoa and its role in regulating the tyrosine phosphorylation events associated with sperm capacitation. Biol Reprod 69:347–354PubMedGoogle Scholar
  54. Fischer MA, Willis J, Zini A (2003) Human sperm DNA integrity: correlation with sperm cytoplasmic droplets. Urology 61:207–211PubMedGoogle Scholar
  55. Ford WC (2004) Regulation of sperm function by reactive oxygen species. Hum Reprod Update 10:387–399PubMedGoogle Scholar
  56. 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 17:276–287PubMedGoogle Scholar
  57. Gomez E, Irvine DS, Aitken RJ (1998) Evaluation of a spectrophotometric assay for the measurement of malondialdehyde and 4-hydroxyalkenals in human spermatozoa: relationships with semen quality and sperm function. Int J Androl 21:81–94PubMedGoogle Scholar
  58. Griveau JF, Renard P, Le Lannou D (1994) An in vitro promoting role for hydrogen peroxide in human sperm capacitation. Int J Androl 17:300–307PubMedGoogle Scholar
  59. Hecht D, Zick Y (1992) Selective inhibition of protein tyrosine phosphatase activities by H2O2 and vanadate in vitro. Biochem Biophys Res Commun 188:773–779PubMedGoogle Scholar
  60. Herrero MB, Perez Martinez S, Viggiano JM, Polak JM, Gimeno MF (1996) Localization by indirect immunofluorescence of nitric oxidase synthase in mouse and human spermatozoa. Reprod Fertil Dev 8:931–934PubMedGoogle Scholar
  61. Herrero MB, de Lamirande E, Gagnon C (2001) Tyrosine nitration in human spermatozoa: a physiological function of peroxynitrite, the reaction product of nitric oxide and superoxide. Mol Hum Reprod 7:913–921PubMedGoogle Scholar
  62. Herrero MB, de Lamirande E, Gagnon C (2003) Nitric oxide is a signaling molecule in spermatozoa. Curr Pharm Des 9:419–425PubMedGoogle Scholar
  63. Hong CY, Chiang BN, Turner P (1984) Calcium ion is the key regulator of human sperm function. Lancet December 22:1449–1451Google Scholar
  64. Huszar G, Ozkavukcu S, Jakab A, Celik-Ozenci C, Sati GL, Cayli S (2006) Hyaluronic acid binding ability of human sperm reflects cellular maturity and fertilizing potential: selection of sperm for intracytoplasmic sperm injection. Curr Opin Obstet Gynecol 18:260–267PubMedGoogle Scholar
  65. Iuchi Y, Okada F, Tsunoda S, Kibe N, Shirasawa N, Ikawa M, Okabe M, Ikeda Y, Fujii J (2008) Peroxiredoxin 4 knockout results in elevated spermatogenic cell death via oxidative stress. Biochem J 419(1):149–158Google Scholar
  66. Jones R, Mann T, Sherins R (1979) Peroxidative breakdown of phospholipids in human spermatozoa, spermicidal properties of fatty acid peroxides, and protective action of seminal plasma. Fertil Steril 31:531–537PubMedGoogle Scholar
  67. Kadirvel G, Kumar S, Kumaresan A (2009) Lipid peroxidation, mitochondrial membrane potential and DNA integrity of spermatozoa in relation to intracellular reactive oxygen species in liquid and frozen-thawed buffalo semen. Anim Reprod Sci 114(1–3):125–134PubMedGoogle Scholar
  68. Koppers AJ, De Iuliis GN, Finnie JM, McLaughlin EA, Aitken RJ (2008) Significance of mitochondrial reactive oxygen species in the generation of oxidative stress in spermatozoa. J Clin Endocrinol Metab 93:3199–3207PubMedGoogle Scholar
  69. 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 22:643–656PubMedGoogle Scholar
  70. Leclerc P, de Lamirande E, 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 19:434–443PubMedGoogle Scholar
  71. Lewis B, Aitken RJ (2001) A redox-regulated tyrosine phosphorylation cascade in rat spermatozoa. J Androl 22:611–622PubMedGoogle Scholar
  72. Li Y, Trush MA (1998) Diphenyleneiodonium, an NAD(P)H oxidase inhibitor, also potently inhibits mitochondrial reactive oxygen species production. Biochem Biophys Res Commun 253:295–299PubMedGoogle Scholar
  73. Li Z, Yang J, Huang H (2006) Oxidative stress induces H2AX phosphorylation in human spermatozoa. FEBS Lett 580:6161–6168PubMedGoogle Scholar
  74. Lin M, Lee YH, Xu W, Baker MA, Aitken RJ (2006) Ontogeny of tyrosine phosphorylation-signaling pathways during spermatogenesis and epididymal maturation in the mouse. Biol Reprod 75:588–597PubMedGoogle Scholar
  75. McKelvey-Martin VJ, Melia N, Walsh IK, Johnston SR, Hughes CM, Lewis SE, Thompson W (1997) Two potential clinical applications of the alkaline single-cell gel electrophoresis assay: (1) Human bladder washings and transitional cell carcinoma of the bladder; and (2) Human sperm and male infertility. Mutat Res 375:93–104PubMedGoogle Scholar
  76. McLachlan RI, de Kretser DM (2001) Male infertility: the case for continued research. Med J Aust 174:116–117PubMedGoogle Scholar
  77. Miranda-Vizuete A, Sadek CM, Jiménez A, Krause WJ, Sutovsky P, Oko R (2004) The mammalian testis-specific thioredoxin system. Antioxid Redox Signal 6:25–40PubMedGoogle Scholar
  78. Nakashima I, Takeda K, Kawamoto Y, Okuno Y, Kato M, Suzuki H (2005) Redox control of catalytic activities of membrane-associated protein tyrosine kinases. Arch Biochem Biophys 434:3–10PubMedGoogle Scholar
  79. Nuti F, Krausz C (2008) Gene polymorphisms/mutations relevant to abnormal spermatogenesis. Reprod Biomed Online 16(5):04–513Google Scholar
  80. O’Flaherty C, de Lamirande E, Gagnon C (2006) Positive role of reactive oxygen species in mammalian sperm capacitation: triggering and modulation of phosphorylation events. Free Radic Biol Med 41:528–540PubMedGoogle Scholar
  81. O’Flaherty C, Beorlegui N, Beconi MT (2003) Participation of superoxide anion in the capacitation of cryopreserved bovine sperm. Int J Androl 26:109–114PubMedGoogle Scholar
  82. Paul C, Murray AA, Spears N, Saunders PT (2008) A single, mild, transient scrotal heat stress causes DNA damage, subfertility and impairs formation of blastocysts in mice. Reproduction 136:73–84PubMedGoogle Scholar
  83. Piña-Guzmán B, Solís-Heredia MJ, Rojas-García AE, Urióstegui-Acosta M, Quintanilla-Vega B (2006) Genetic damage caused by methyl-parathion in mouse spermatozoa is related to oxidative stress. Toxicol Appl Pharmacol 216:216–224PubMedGoogle Scholar
  84. Plastira K, Msaouel P, Angelopoulou R, Zanioti K, Plastiras A, Pothos A, Bolaris S, Paparisteidis N, Mantas D (2007) The effects of age on DNA fragmentation, chromatin packaging and conventional semen parameters in spermatozoa of oligoasthenoteratozoospermic patients. J Assist Reprod Genet 24:437–443PubMedGoogle Scholar
  85. Rivlin J, Mendel J, Rubinstein S, Etkovitz N, Breitbart H (2004) Role of hydrogen peroxide in sperm capacitation and acrosome reaction. Biol Reprod 70:518–522PubMedGoogle Scholar
  86. Roy SC, Atreja SK (2008) Effect of reactive oxygen species on capacitation and associated protein tyrosine phosphorylation in buffalo (Bubalus bubalis) spermatozoa. Anim Reprod Sci 107:68–84PubMedGoogle Scholar
  87. Sabeur K, Ball BA (2007) Characterization of NADPH oxidase 5 in equine testis and spermatozoa. Reproduction 134:263–270PubMedGoogle Scholar
  88. Sakkas D, Urner F, Bizzaro D, Manicardi G, Bianchi PG, Shoukir Y, Campana A (1998) Sperm nuclear DNA damage and altered chromatin structure: effect on fertilization and embryo development. Hum Reprod 13(Suppl 4):11–29PubMedGoogle Scholar
  89. Sawyer DE, Mercer BG, Wiklendt AM, Aitken RJ (2003) Quantitative analysis of gene-specific DNA damage in human spermatozoa. Mutat Res 529:21–34PubMedGoogle Scholar
  90. Sega GA (1991) Adducts in sperm protamine and DNA vs. mutation frequency. Prog Clin Biol Res 372:521–530PubMedGoogle Scholar
  91. Shukla S, Jha RK, Laloraya M, Kumar PG (2005) Identification of non-mitochondrial NADPH oxidase and the spatio-temporal organization of its components in mouse spermatozoa. Biochem Biophys Res Commun 331:476–483PubMedGoogle Scholar
  92. Spermon JR, Ramos L, Wetzels AM, Sweep CG, Braat DD, Kiemeney LA, Witjes JA (2006) Sperm integrity pre- and post-chemotherapy in men with testicular germ cell cancer. Hum Reprod 21:1781–1786PubMedGoogle Scholar
  93. Suleiman SA, Elamin Ali M, Zaki ZMS, El-Malik EMA, Nasr MA (1996) Lipid peroxidation and human sperm motility: protective role of vitamin E. J Androl 17:530–537PubMedGoogle Scholar
  94. Tosic J, Walton A (1946) Formation of hydrogen peroxide by spermatozoa and its inhibitory effect on respiration. Nature 158:485PubMedGoogle Scholar
  95. Tremellen K (2008) Oxidative stress and male infertility – a clinical perspective. Hum Reprod Update 14:243–258PubMedGoogle Scholar
  96. Urner F, Sakkas D (2003) Protein phosphorylation in mammalian spermatozoa. Reproduction 125:17–26PubMedGoogle Scholar
  97. Verma A, Kanwar KC (1999) Effect of vitamin E on human sperm motility and lipid peroxidation in vitro. Asian J Androl 1:151–154PubMedGoogle Scholar
  98. Vernet P, Fulton N, Wallace C, Aitken RJ (2001) Analysis of reactive oxygen species generating systems in rat epididymal spermatozoa. Biol Reprod 65:1102–1113PubMedGoogle Scholar
  99. Visconti PE, Moore GD, Bailey JL, Leclerc P, Connors SA, Pan D, Olds-Clarke P, Kopf GS (1995) Capacitation of mouse spermatozoa. II. Protein tyrosine phosphorylation and capacitation are regulated by a cAMP-dependent pathway. Development 121:1139–1150PubMedGoogle Scholar
  100. Vorup-Jensen T, Hjort T, Abraham-Peskir JV, Guttmann P, Jensenius JC, Uggerhøj E, Medenwaldt R (1999) X-ray microscopy of human spermatozoa shows change of mitochondrial morphology after capacitation. Hum Reprod 14:880–884PubMedGoogle Scholar
  101. Zhang H, Zheng R-L (1996) Promotion of human sperm capacitation by superoxide anion. Free Rad Res 24:261–268Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  • R. John Aitken
    • 1
  • Mark A. Baker
    • 1
  • Geoffry N. De Iuliis
    • 1
  • Brett Nixon
    • 1
  1. 1.ARC Centre of Excellence in Biotechnology and Development, Hunter Medical Research Institute, Discipline of Biological SciencesUniversity of NewcastleCallaghanAustralia

Personalised recommendations