Spermatogenesis: An Overview

Abstract

The purpose of this chapter is to provide a comprehensive overview of spermatogenesis and the various steps involved in the development of the male gamete, including cellular processes and nuclear transformations that occur during spermatogenesis, to provide a clear understanding of one of the most complex cellular metamorphosis that occurs in the human body. Spermatogenesis is a highly complex temporal event during which a relatively undifferentiated diploid cell called spermatogonium slowly evolves into a highly specialized haploid cell called spermatozoon. The goal of spermatogenesis is to produce a genetically unique male gamete that can fertilize an ovum and produce offspring. It involves a series of intricate, cellular, proliferative, and developmental phases. Spermatogenesis is initiated through the neurological axis by the hypothalamus, which releases gonadotropin-releasing hormone, which in turn signals follicle-stimulating hormone (FSH) and luteinizing hormone (LH) to be transmitted to the reproductive tract. LH interacts with the Leydig cells to produce testosterone, and FSH interacts with the Sertoli cells that provide support and nutrition for sperm proliferation and development. Spermatogenesis involves a series of cell phases and divisions by which the diploid spermatogonial cells develop into primary spermatocytes via mitosis. Primary spermatocytes in the basal compartment of Sertoli cells undergo meiosis to produce haploid secondary spermatocytes in the ­adluminal compartment of Sertoli cells in a process called spermatocytogenesis. This process gives the cells a unique genetic identity within the population of secondary spermatocytes and subsequent developing cells. After spermatocytogenesis, spermatids elongate to form spermatozoa by spermiogenesis, a morphological development phase in which the nuclear transformations involving chromatin remodeling and compaction occur. Spermatozoa then leave the Sertoli cells through the lumen of the seminiferous tubules, exit through the rete testis, and enter the epididymis for final maturation. This is where spermatozoa acquire motility and acrosomal function. Spermatogenesis in the human male takes about 74 days. Spermatogenesis is regulated by intrinsic and extrinsic factors. Not all spermatogonia mature into spermatozoa – most are eliminated and phagocytosed in a process called apoptosis. The overall goals of spermatogenesis are (1) to enable the male to transfer genetically recombined DNA by contributing to half of the offspring’s genome and (2) to equip the spermatozoa to effectively navigate through the female reproductive tract and deliver the genetic material to the ovum. In the following sections, the complex transformation of the simple single diploid cell into a fully functional haploid cell is described.

Keywords

Spermatogenesis Male gamete Neurological pathways in spermatogenesis Spermiogenesis Meiosis and mitosis 

References

  1. 1.
    Wilson JD. Syndromes of androgen resistance. Biol Reprod. 1992;46:168–73.PubMedGoogle Scholar
  2. 2.
    Lubahn DB, Moyer JS, Golding TS, Couse JF, Korach KS, Smithies O. Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene. Proc Natl Acad Sci USA. 1993;90:11162–6.PubMedGoogle Scholar
  3. 3.
    Smith EP, Boyd J, Frank GR, Takahashi H, Cohen RM, Specker B, et al. Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N Engl J Med. 1994;331:1056–61.PubMedGoogle Scholar
  4. 4.
    Tishler PV. Diameter of testicles. N Engl J Med. 1971;285:1489.PubMedGoogle Scholar
  5. 5.
    Winter JS, Faiman C. Pituitary-gonadal relations in male children and adolescents. Pediatr Res. 1972;6:126–35.PubMedGoogle Scholar
  6. 6.
    Middendorff R, Müller D, Mewe M, Mukhopadhyay AK, Holstein AF, Davidoff MS. The tunica albuginea of the human testis is characterized by complex contraction and relaxation activities regulated by cyclic GMP. J Clin Endocrinol Metab. 2002;87:3486–99.PubMedGoogle Scholar
  7. 7.
    Prader A. Testicular size: assessment and clinical importance. Triangle. 1966;7:240–3.PubMedGoogle Scholar
  8. 8.
    Agger P. Scrotal and testicular temperature: its ­relation to sperm count before and after operation for varicocele. Fertil Steril. 1971;22:286–97.PubMedGoogle Scholar
  9. 9.
    de Kretser DM, Temple-Smith PD, Kerr JB. Anatomical and functional aspects of the male reproductive organs. In: Bandhauer K, Fricks J, editors. Handbook of urology, vol. XVI. Berlin: Springer; 1982. p. 1–131.Google Scholar
  10. 10.
    Christensen AK. Leydig cells. In: Hamilton DW, Greep RO, editors. Handbook of physiology. Baltimore: Williams and Wilkins; 1975. p. 57–94.Google Scholar
  11. 11.
    Kaler LW, Neaves WB. Attrition of the human Leydig cell population with advancing age. Anat Rec. 1978;192:513–8.PubMedGoogle Scholar
  12. 12.
    DeKretser DM, Kerr JB. The cytology of the testis. In: Knobill E, Neil JD, editors. The physiology of reproduction. New York: Raven; 1994. p. 1177–290.Google Scholar
  13. 13.
    Payne AH, Wong KL, Vega MM. Differential effects of single and repeated administrations of gonadotropins on luteinizing hormone receptors and testosterone synthesis in two populations of Leydig cells. J Biol Chem. 1980;255:7118–22.PubMedGoogle Scholar
  14. 14.
    Glover TD, Barratt CLR, Tyler JJP, Hennessey JF. Human male fertility. London: Academic; 1980. p. 247.Google Scholar
  15. 15.
    Ewing LL, Keeney DS. Leydig cells: structure and function. In: Desjardins C, Ewin LL, editors. Cell and molecular biology of the testis. New York: Oxford University Press; 1993.Google Scholar
  16. 16.
    Davidoff MS, Breucker H, Holstein AF, Seidel K. Cellular architecture of the lamina propria of human tubules. Cell Tissue Res. 1990;262:253–61.PubMedGoogle Scholar
  17. 17.
    Roosen-Runge EC, Holstein A. The human rete testis. Cell Tissue Res. 1978;189:409–33.PubMedGoogle Scholar
  18. 18.
    Russell LD, Griswold MD, editors. The Sertoli cell. Clearwater: Cache Press; 1993.Google Scholar
  19. 19.
    de França LR, Ghosh S, Ye SJ, Russell LD. Surface and surface-to-volume relationships of the Sertoli cell during the cycle of the seminiferous epithelium in the rat. Biol Reprod. 1993;49:1215–28.PubMedGoogle Scholar
  20. 20.
    Behringer RR. The müllerian inhibitor and mammalian sexual development. Philos Trans R Soc Lond B Biol Sci. 1995;350:285–8.PubMedGoogle Scholar
  21. 21.
    Josso N, di Clemente N, Gouédard L. Anti-Müllerian hormone and its receptors. Mol Cell Endocrinol. 2001;179:25–32.PubMedGoogle Scholar
  22. 22.
    Clermont Y. Kinetics of spermatogenesis in mammals: seminiferous epithelium cycle and spermatogonial renewal. Physiol Rev. 1972;52:198–236.PubMedGoogle Scholar
  23. 23.
    Clermont Y. The cycle of the seminiferous epithelium in man. Am J Anat. 1963;112:35–51.PubMedGoogle Scholar
  24. 24.
    Schulze C. Morphological characteristics of the spermatogonial stem cells in man. Cell Tissue Res. 1974;198:191–9.Google Scholar
  25. 25.
    Clermont Y, Bustos-Obregon E. Re-examination of spermatogonial renewal in the rat by means of seminiferous tubules mounted “in toto”. Am J Anat. 1968;122:237–47.PubMedGoogle Scholar
  26. 26.
    Huckins C. The spermatogonial stem cell population in adult rats. I. Their morphology, proliferation and maturation. Anat Rec. 1971;169:533–57.PubMedGoogle Scholar
  27. 27.
    Dym M, Fawcett DW. Further observations on the numbers of spermatogonia, spermatocytes, and spermatids connected by intercellular bridges in the mammalian testis. Biol Reprod. 1971;4:195–215.PubMedGoogle Scholar
  28. 28.
    Berezney R, Coffey DS. Nuclear matrix. Isolation and characterization of a framework structure from rat liver nuclei. J Cell Biol. 1977;73:616–37.PubMedGoogle Scholar
  29. 29.
    Mirkovitch J, Mirault ME, Laemmli UK. Organization of the higher-order chromatin loop: specific DNA attachment sites on nuclear scaffold. Cell. 1984;39:223–32.PubMedGoogle Scholar
  30. 30.
    Gasse S. Studies on scaffold attachment sites and their relation to genome function. Int Rev Cytol. 1989;119:57.Google Scholar
  31. 31.
    Izaurralde E, Kas E, Laemmli UK. Highly preferential nucleation of histone H1 assembly on scaffold-associated regions. J Mol Biol. 1989;210:573–85.PubMedGoogle Scholar
  32. 32.
    Adachi Y, Kas E, Laemmli UK. Preferential cooperative binding of DNA topoisomerase II to scaffold-associated regions. EMBO J. 1989;13:3997.Google Scholar
  33. 33.
    Dickinson LA, Joh T, Kohwi Y, Kohwi-Shigematsu T. A tissue-specific MAR/SAR DNA-binding protein with unusual binding site recognition. Cell. 1992;70:631–45.PubMedGoogle Scholar
  34. 34.
    Breucker H, Schäfer E, Holstein AF. Morphogenesis and fate of the residual body in human spermiogenesis. Cell Tissue Res. 1985;240:303–9.PubMedGoogle Scholar
  35. 35.
    Leblond CP, Clermont Y. Definition of the stages of the cycle of the seminiferous epithelium in the rat. Ann N Y Acad Sci. 1952;55:548–73.PubMedGoogle Scholar
  36. 36.
    Clermont Y, Perey B. The stages of the cycle of the seminiferous epithelium of the rat: practical definitions in PA-Schiff-hematoxylin and hematoxylin-eosin stained sections. Rev Can Biol. 1957;16:451–62.PubMedGoogle Scholar
  37. 37.
    Schulze W, Rehder U. Organization and morphogenesis of the human seminiferous epithelium. Cell Tissue Res. 1984;237:395–407.PubMedGoogle Scholar
  38. 38.
    Ward WS, Coffey DS. DNA packaging and organization in mammalian spermatozoa: comparison with somatic cells. Biol Reprod. 1991;44:569–74.PubMedGoogle Scholar
  39. 39.
    McGhee JD, Felsenfeld G, Eisenberg H. Nucleosome structure and conformational changes. Biophys J. 1980;32:261–70.PubMedGoogle Scholar
  40. 40.
    Sassone-Corsi P. Unique chromatin remodeling and transcriptional regulation in spermatogenesis. Science. 2002;296:2176–8.PubMedGoogle Scholar
  41. 41.
    Dadoune JP, Siffroi JP, Alfonsi MF. Transcription in haploid male germ cells. Int Rev Cytol. 2004;237:1–56.PubMedGoogle Scholar
  42. 42.
    Ward WS, Partin AW, Coffey DS. DNA loop domains in mammalian spermatozoa. Chromosoma. 1989;98:153–9.PubMedGoogle Scholar
  43. 43.
    McPherson S, Longo FJ. Chromatin structure-function alterations during mammalian spermatogenesis: DNA nicking and repair in elongating spermatids. Eur J Histochem. 1993;37:109–28.PubMedGoogle Scholar
  44. 44.
    Allen MJ, Lee C, Lee IV JD, Pogany GC, Balooch M, Siekhaus WJ, et al. Atomic force microscopy of mammalian sperm chromatin. Chromosoma. 1993;102:623–30.PubMedGoogle Scholar
  45. 45.
    Lewis JD, Abbott DW, Ausió J. A haploid affair: core histone transitions during spermatogenesis. Biochem Cell Biol. 2003;81:131–40.PubMedGoogle Scholar
  46. 46.
    Lewis JD, Song Y, de Jong ME, Bagha SM, Ausió J. A walk though vertebrate and invertebrate protamines. Chromosoma. 2003;111:473–82.PubMedGoogle Scholar
  47. 47.
    Braun RE. Packaging paternal chromosomes with protamine. Nat Genet. 2001;28:10–2.PubMedGoogle Scholar
  48. 48.
    Wu TF, Chu DS. Sperm chromatin: fertile grounds for proteomic discovery of clinical tools. Mol Cell Proteomics. 2008;7:1876–86.PubMedGoogle Scholar
  49. 49.
    Ooi SL, Henikoff S. Germline histone dynamics and epigenetics. Curr Opin Cell Biol. 2007;19:257–65.PubMedGoogle Scholar
  50. 50.
    Cho C, Willis WD, Goulding EH, Jung-Ha H, Choi YC, Hecht NB, et al. Haploinsufficiency of protamine-1 or -2 causes infertility in mice. Nat Genet. 2001;28:82–6.PubMedGoogle Scholar
  51. 51.
    Yu YE, Zhang Y, Unni E, Shirley CR, Deng JM, Russell LD, et al. Abnormal spermatogenesis and reduced ­fertility in transition nuclear protein 1-deficient mice. Proc Natl Acad Sci USA. 2000;97:4683–8.PubMedGoogle Scholar
  52. 52.
    Zhao M, Shirley CR, Yu YE, Mohapatra B, Zhang Y, Unni E, et al. Targeted disruption of the transition protein 2 gene affects sperm chromatin structure and reduces fertility in mice. Mol Cell Biol. 2001;21:7243–55.PubMedGoogle Scholar
  53. 53.
    Churikov D, Zalenskaya IA, Zalensky AO. Male germline-specific histones in mouse and man. Cytogenet Genome Res. 2004;105:203–14.PubMedGoogle Scholar
  54. 54.
    Dadoune JP. The nuclear status of human sperm cells. Micron. 1995;26:323–45.PubMedGoogle Scholar
  55. 55.
    Kierszenbaum AL. Transition nuclear proteins during spermiogenesis: unrepaired DNA breaks not allowed. Mol Reprod Dev. 2001;58:357–8.PubMedGoogle Scholar
  56. 56.
    Lee CH, Cho YH. Aspects of mammalian spermatogenesis: electrophoretical analysis of protamines in mammalian species. Mol Cells. 1999;9:556–9.PubMedGoogle Scholar
  57. 57.
    Bench GS, Friz AM, Corzett MH, Morse DH, Balhorn R. DNA and total protamine masses in ­individual sperm from fertile mammalian subjects. Cytometry. 1996;23:263–71.PubMedGoogle Scholar
  58. 58.
    Gatewood JM, Cook GR, Balhorn R, Bradbury EM, Schmid CW. Sequence-specific packaging of DNA in human sperm chromatin. Science. 1987;236:962–4.PubMedGoogle Scholar
  59. 59.
    Laberge RM, Boissonneault G. On the nature and origin of DNA strand breaks in elongating spermatids. Biol Reprod. 2005;73:289–96.PubMedGoogle Scholar
  60. 60.
    Marcon L, Boissonneault G. Transient DNA strand breaks during mouse and human spermiogenesis new insights in stage specificity and link to chromatin remodeling. Biol Reprod. 2004;70:910–8.PubMedGoogle Scholar
  61. 61.
    McPherson SM, Longo FJ. Nicking of rat spermatid and spermatozoa DNA: possible involvement of DNA topoisomerase II. Dev Biol. 1993;158:122–30.PubMedGoogle Scholar
  62. 62.
    Muratori M, Marchiani S, Maggi M, Forti G, Baldi E. Origin and biological significance of DNA fragmentation in human spermatozoa. Front Biosci. 2006;11:1491–9.PubMedGoogle Scholar
  63. 63.
    Zhao M, Shirley CR, Mounsey S, Meistrich ML. Nucleoprotein transitions during spermiogenesis in mice with transition nuclear protein Tnp1 and Tnp2 mutations. Biol Reprod. 2004;71:1016–25.PubMedGoogle Scholar
  64. 64.
    Kistler WS, Noyes C, Hsu R, Heinrikson RL. The amino acid sequence of a testis-specific basic protein that is associated with spermatogenesis. J Biol Chem. 1975;250:1847–53.PubMedGoogle Scholar
  65. 65.
    Kleene KC, Borzorgzadeh A, Flynn JF, Yelick PC, Hecht NB. Nucleotide sequence of a cDNA clone encoding mouse transition protein 1. Biochim Biophys Acta. 1988;950:215–20.PubMedGoogle Scholar
  66. 66.
    Schlüter G, Celik A, Obata R, Schlicker M, Hofferbert S, Schlung A, et al. Sequence analysis of the conserved protamine gene cluster shows that it contains a fourth expressed gene. Mol Reprod Dev. 1996;43:1–6.PubMedGoogle Scholar
  67. 67.
    Meistrich ML. Calculation of the incidence of infertility in human populations from sperm measures using the two-distribution model. Prog Clin Biol Res. 1989;302:275–85.PubMedGoogle Scholar
  68. 68.
    Alfonso PJ, Kistler WS. Immunohistochemical localization of spermatid nuclear transition protein 2 in the testes of rats and mice. Biol Reprod. 1993;48:522–9.PubMedGoogle Scholar
  69. 69.
    Heidaran MA, Showman RM, Kistler WS. A cytochemical study of the transcriptional and translational regulation of nuclear transition protein 1 (TP1), a major chromosomal protein of mammalian spermatids. J Cell Biol. 1988;106:1427–33.PubMedGoogle Scholar
  70. 70.
    Baskaran R, Rao MR. Interaction of spermatid-specific protein TP2 with nucleic acids, in vitro. A comparative study with TP1. J Biol Chem. 1990;265:21039–47.PubMedGoogle Scholar
  71. 71.
    Lévesque D, Veilleux S, Caron N, Boissonneault G. Architectural DNA-binding properties of the spermatidal transition proteins 1 and 2. Biochem Biophys Res Commun. 1998;252:602–9.PubMedGoogle Scholar
  72. 72.
    Kundu TK, Rao MR. Zinc dependent recognition of a human CpG island sequence by the mammalian spermatidal protein TP2. Biochemistry. 1996;35:15626–32.PubMedGoogle Scholar
  73. 73.
    Boissonneault G. Chromatin remodeling during spermiogenesis: a possible role for the transition proteins in DNA strand break repair. FEBS Lett. 2002;514:111–4.PubMedGoogle Scholar
  74. 74.
    Caron N, Veilleux S, Boissonneault G. Stimulation of DNA repair by the spermatidal TP1 protein. Mol Reprod Dev. 2001;58:437–43.PubMedGoogle Scholar
  75. 75.
    Brewer L, Corzett M, Balhorn R. Condensation of DNA by spermatid basic nuclear proteins. J Biol Chem. 2002;277:38895–900.PubMedGoogle Scholar
  76. 76.
    Adham IM, Nayernia K, Burkhardt-Göttges E, Topaloglu O, Dixkens C, Holstein AF, et al. Teratozoospermia in mice lacking the transition ­protein 2 (Tnp2). Mol Hum Reprod. 2001;7:513–20.PubMedGoogle Scholar
  77. 77.
    Carrell DT, Liu L. Altered protamine 2 expression is uncommon in donors of known fertility, but common among men with poor fertilizing capacity, and may reflect other abnormalities of spermiogenesis. J Androl. 2001;22:604–10.PubMedGoogle Scholar
  78. 78.
    de Yebra L, Ballescá JL, Vanrell JA, Corzett M, Balhorn R, Oliva R. Detection of P2 precursors in the sperm cells of infertile patients who have reduced protamine P2 levels. Fertil Steril. 1998;69:755–9.PubMedGoogle Scholar
  79. 79.
    Balhorn R, Corzett M, Mazrimas JA. Formation of intraprotamine disulfides in vitro. Arch Biochem Biophys. 1992;296:384–93.PubMedGoogle Scholar
  80. 80.
    Balhorn R, Cosman M, Thornton K, Krishnan VV, Corzett M, Bench G, et al. Protamine-mediated condensation of DNA in mammalian sperm. In: Gagnon C, editor. The male gamete: from basic science to ­clinical applications. Vienna: Cache River Press; 1999.Google Scholar
  81. 81.
    Corzett M, Mazrimas J, Balhorn R. Protamine 1: protamine 2 stoichiometry in the sperm of eutherian mammals. Mol Reprod Dev. 2002;61:519–27.PubMedGoogle Scholar
  82. 82.
    Fuentes-Mascorro G, Serrano H, Rosado A. Sperm chromatin. Arch Androl. 2000;45:215–25.PubMedGoogle Scholar
  83. 83.
    Dixon GH, Aiken JM, Jankowski JM, McKenzie D, Moir R, States JC, et al. Organization and evolution of protamine gene of salmoind fishes. In: Reeck GR, Goodwin GH, Puigdomenech P, editors. Chromosomal proteins and gene expression. New York: Plenum; 1986.Google Scholar
  84. 84.
    Krawetz SA, Dixon GH. Sequence similarities of the protamine genes: implications for regulation and evolution. J Mol Evol. 1988;27:291–7.PubMedGoogle Scholar
  85. 85.
    Balhorn R, Brewer L, Corzett M. DNA condensation by protamine and arginine-rich peptides: analysis of toroid stability using single DNA molecules. Mol Reprod Dev. 2000;56:230–4.PubMedGoogle Scholar
  86. 86.
    Courtens JL, Loir M. Ultrastructural detection of basic nucleoproteins: alcoholic phosphotungstic acid does not bind to arginine residues. J Ultrastruct Res. 1981;74:322–6.PubMedGoogle Scholar
  87. 87.
    Loir M, Lanneau M. Structural function of the basic nuclear proteins in ram spermatids. J Ultrastruct Res. 1984;86:262–72.PubMedGoogle Scholar
  88. 88.
    Singh J, Rao MR. Interaction of rat testis protein, TP, with nucleosome core particle. Biochem Int. 1988;17:701–10.PubMedGoogle Scholar
  89. 89.
    Le Lannic G, Arkhis A, Vendrely E, Chevaillier P, Dadoune JP. Production, characterization, and immunocytochemical applications of monoclonal antibodies to human sperm protamines. Mol Reprod Dev. 1993;36:106–12.PubMedGoogle Scholar
  90. 90.
    Szczygiel MA, Ward WS. Combination of dithiothreitol and detergent treatment of spermatozoa causes paternal chromosomal damage. Biol Reprod. 2002;67:1532–7.PubMedGoogle Scholar
  91. 91.
    Hecht NB. Post-meiotic gene expression during spermatogenesis. Prog Clin Biol Res. 1988;267:291–313.PubMedGoogle Scholar
  92. 92.
    Hecht NB. Regulation of ‘haploid expressed genes’ in male germ cells. J Reprod Fertil. 1990;88:679–93.PubMedGoogle Scholar
  93. 93.
    Oliva R, Dixon GH. Vertebrate protamine gene evolution I. Sequence alignments and gene structure. J Mol Evol. 1990;30:333–46.PubMedGoogle Scholar
  94. 94.
    Steger K. Transcriptional and translational regulation of gene expression in haploid spermatids. Anat Embryol (Berl). 1999;199:471–87.Google Scholar
  95. 95.
    Oliva R. Protamines and male infertility. Hum Reprod Update. 2006;12:417–35.PubMedGoogle Scholar
  96. 96.
    Chevaillier P, Mauro N, Feneux D, Jouannet P, David G. Anomalous protein complement of sperm nuclei in some infertile men. Lancet. 1987;2:806–7.PubMedGoogle Scholar
  97. 97.
    Balhorn R, Reed S, Tanphaichitr N. Aberrant protamine 1/protamine 2 ratios in sperm of infertile human males. Experientia. 1988;44:52–5.PubMedGoogle Scholar
  98. 98.
    Aoki VW, Moskovtsev SI, Willis J, Liu L, Mullen JB, Carrell DT. DNA integrity is compromised in protamine-deficient human sperm. J Androl. 2005;26:741–8.PubMedGoogle Scholar
  99. 99.
    Carrell DT, Emery BR, Hammoud S. Altered protamine expression and diminished spermatogenesis: what is the link? Hum Reprod Update. 2007;13:313–27.PubMedGoogle Scholar
  100. 100.
    Kosower NS, Katayose H, Yanagimachi R. Thiol-disulfide status and acridine orange fluorescence of mammalian sperm nuclei. J Androl. 1992;13:342–8.PubMedGoogle Scholar
  101. 101.
    Sakkas D, Mariethoz E, Manicardi G, et al. Origin of DNA damage in ejaculated human spermatozoa. Rev Reprod. 1999;4:31–7.PubMedGoogle Scholar
  102. 102.
    Aoki VW, Carrell DT. Human protamines and the developing spermatid: their structure, function, expression and relationship with male infertility. Asian J Androl. 2003;5:315–24.PubMedGoogle Scholar
  103. 103.
    Mengual L, Ballescá JL, Ascaso C, Oliva R. Marked differences in protamine content and P1/P2 ratios in sperm cells from percoll fractions between patients and controls. J Androl. 2003;24:438–47.PubMedGoogle Scholar
  104. 104.
    Steger K, Pauls K, Klonisch T, Franke FE, Bergmann M. Expression of protamine-1 and -2 mRNA during human spermiogenesis. Mol Hum Reprod. 2000;6:219–25.PubMedGoogle Scholar
  105. 105.
    Rousseaux S, Caron C, Govin J, Lestrat C, Faure AK, Khochbin S. Establishment of male-specific epigenetic information. Gene. 2005;345:139–53.PubMedGoogle Scholar
  106. 106.
    Arpanahi A, Brinkworth M, Iles D, Krawetz SA, Paradowska A, Platts AE, et al. Endonuclease-sensitive regions of human spermatozoal chromatin are highly enriched in promoter and CTCF binding sequences. Genome Res. 2009;19:1338–49.PubMedGoogle Scholar
  107. 107.
    Hammoud SS, Purwar J, Pflueger C, Cairns BR, Carrell DT. Alterations in sperm DNA methylation patterns at imprinted loci in two classes of infertility. Fertil Steril. 2010;94:1728–33.PubMedGoogle Scholar
  108. 108.
    Razin A, Riggs AD. DNA methylation and gene function. Science. 1980;210:604–10.PubMedGoogle Scholar
  109. 109.
    Cedar H. DNA methylation and gene expression. In: Razin A, Cedar H, Riggs AD, editors. DNA methylation: biochemistry and biological significance. New York: Springer; 1985.Google Scholar
  110. 110.
    Sanford JP, Clark HJ, Chapman VM, Rossant J. Differences in DNA methylation during oogenesis and spermatogenesis and their persistence during early embryogenesis in the mouse. Genes Dev. 1987;1:1039–46.PubMedGoogle Scholar
  111. 111.
    Rahe B, Erickson RP, Quinto M. Methylation of unique sequence DNA during spermatogenesis in mice. Nucleic Acids Res. 1983;11:7947–59.PubMedGoogle Scholar
  112. 112.
    Trasler JM. Epigenetics in spermatogenesis. Mol Cell Endocrinol. 2009;306:33–6.PubMedGoogle Scholar
  113. 113.
    Oakes CC, La Salle S, Smiraglia DJ, Robaire B, Trasler JM. Developmental acquisition of genome-wide DNA methylation occurs prior to meiosis in male germ cells. Dev Biol. 2007;307:368–79.PubMedGoogle Scholar
  114. 114.
    Benchaib M, Braun V, Lornage J, et al. Sperm DNA fragmentation decreases the pregnancy rate in an assisted reproductive technique. Hum Reprod. 2003;18:1023–8.PubMedGoogle Scholar
  115. 115.
    Ward WS. The structure of the sleeping genome: implications of sperm DNA organization for somatic cells. J Cell Biochem. 1994;55:77–82.PubMedGoogle Scholar
  116. 116.
    Risley MS, Einheber S, Bumcrot DA. Changes in DNA topology during spermatogenesis. Chromosoma. 1986;94:217–27.PubMedGoogle Scholar
  117. 117.
    Aitken RJ, De Iuliis GN. On the possible origins of DNA damage in human spermatozoa. Mol Hum Reprod. 2010;16:3–13.PubMedGoogle Scholar
  118. 118.
    Aitken RJ, De Iuliis GN, McLachlan RI. Biological and clinical significance of DNA damage in the male germ line. Int J Androl. 2009;32:46–56.PubMedGoogle Scholar
  119. 119.
    Carrell DT, Emery BR, Hammoud S. The aetiology of sperm protamine abnormalities and their potential impact on the sperm epigenome. Int J Androl. 2008;31:537–45.PubMedGoogle Scholar
  120. 120.
    De Iuliis GN, Thomson LK, Mitchell LA, Finnie JM, Koppers AJ, Hedges A, et al. DNA damage in human spermatozoa is highly correlated with the efficiency of chromatin remodeling and the formation of 8-hydroxy-2´, -deoxyguanosine, a marker of oxidative stress. Biol Reprod. 2009;81:517–24.PubMedGoogle Scholar
  121. 121.
    Leduc F, Maquennehan V, Nkoma GB, Boissonneault G. DNA damage response during chromatin remodeling in elongating spermatids of mice. Biol Reprod. 2008;78:324–32.PubMedGoogle Scholar
  122. 122.
    Kramer JA, Krawetz SA. Nuclear matrix interactions within the sperm genome. J Biol Chem. 1996;271:11619–22.PubMedGoogle Scholar
  123. 123.
    Ward WS, Kimura Y, Yanagimachi R. An intact sperm nuclear matrix may be necessary for the mouse paternal genome to participate in embryonic development. Biol Reprod. 1999;60:702–6.PubMedGoogle Scholar
  124. 124.
    Singleton S, Zalensky A, Doncel GF, Morshedi M, Zalenskaya IA. Testis/sperm-specific histone 2B in the sperm of donors and subfertile patients: variability and relation to chromatin packaging. Hum Reprod. 2007;22:743–50.PubMedGoogle Scholar
  125. 125.
    Iranpour FG, Nasr-Esfahani MH, Valojerdi MR, al-Taraihi TM. Chromomycin A3 staining as a useful tool for evaluation of male fertility. J Assist Reprod Genet. 2000;17:60–6.PubMedGoogle Scholar
  126. 126.
    Bizzaro D, Manicardi GC, Bianchi PG, Bianchi U, Mariethoz E, Sakkas D. In-situ competition between protamine and fluorochromes for sperm DNA. Mol Hum Reprod. 1998;4:127–32.PubMedGoogle Scholar
  127. 127.
    Manicardi GC, Bianchi PG, Pantano S, Azzoni P, Bizzaro D, Bianchi U, et al. Presence of endogenous nicks in DNA of ejaculated human spermatozoa and its relationship to chromomycin A3 accessibility. Biol Reprod. 1995;52:864–7.PubMedGoogle Scholar
  128. 128.
    Bianchi PG, Manicardi GC, Bizzaro D, Bianchi U, Sakkas D. Effect of deoxyribonucleic acid protamination on fluorochrome staining and in situ nick-translation of murine and human mature spermatozoa. Biol Reprod. 1993;49:1083–8.PubMedGoogle Scholar
  129. 129.
    Zini A, Gabriel MS, Zhang X. The histone to protamine ratio in human spermatozoa: comparative study of whole and processed semen. Fertil Steril. 2007;87:217–9.PubMedGoogle Scholar
  130. 130.
    Aoki VW, Emery BR, Liu L, Carrell DT. Protamine levels vary between individual sperm cells of infertile human males and correlate with viability and DNA integrity. J Androl. 2006;27:890–8.PubMedGoogle Scholar
  131. 131.
    Carrell DT, De Jonge C, Lamb DJ. The genetics of male infertility: a field of study whose time is now. Arch Androl. 2006;52:269–74.PubMedGoogle Scholar
  132. 132.
    Irvine DS, Twigg JP, Gordon EL, Fulton N, Milne PA, Aitken RJ. DNA integrity in human spermatozoa: relationships with semen quality. J Androl. 2000;21:33–44.PubMedGoogle Scholar
  133. 133.
    Weng SL, Taylor SL, Morshedi M, Schuffner A, Duran EH, Beebe S, et al. Caspase activity and apoptotic markers in ejaculated human sperm. Mol Hum Reprod. 2002;8:984–91.PubMedGoogle Scholar
  134. 134.
    Sinha Hikim AP, Swerdloff RS. Hormonal and genetic control of germ cell apoptosis in the testis. Rev Reprod. 1999;4:38–47.PubMedGoogle Scholar
  135. 135.
    Rodriguez I, Ody C, Araki K, Garcia I, Vassalli P. An early and massive wave of germinal cell apoptosis is required for the development of functional spermatogenesis. EMBO J. 1997;16:2262–70.PubMedGoogle Scholar
  136. 136.
    Hikim AP, Lue Y, Yamamoto CM, Vera Y, Rodriguez S, Yen PH, et al. Key apoptotic pathways for ­heat-induced programmed germ cell death in the ­testis. Endocrinology. 2003;144:3167–75.PubMedGoogle Scholar
  137. 137.
    Sakkas D, Seli E, Bizzaro D, Tarozzi N, Manicardi GC. Abnormal spermatozoa in the ejaculate: ­abortive apoptosis and faulty nuclear remodelling during spermatogenesis. Reprod Biomed Online. 2003;7:428–32.PubMedGoogle Scholar
  138. 138.
    Paul C, Povey JE, Lawrence NJ, Selfridge J, Melton DW, Saunders PT. Deletion of genes ­implicated in protecting the integrity of male germ cells has ­differential effects on the incidence of DNA breaks and germ cell loss. PLoS One. 2007;3:e989.Google Scholar
  139. 139.
    Bauché F, Fouchard MH, Jégou B. Antioxidant system in rat testicular cells. FEBS Lett. 1994;349:392–6.PubMedGoogle Scholar
  140. 140.
    Fraga CG, Motchnik PA, Wyrobek AJ, Rempel DM, Ames BN. Smoking and low antioxidant levels increase oxidative damage to sperm DNA. Mutat Res. 1996;351:199–203.PubMedGoogle Scholar
  141. 141.
    Meyer-Ficca ML, Lonchar J, Credidio C, Ihara M, Li Y, Wang ZQ, et al. Disruption of poly(ADP-ribose) homeostasis affects spermiogenesis and sperm chromatin integrity in mice. Biol Reprod. 2009;81:46–55.PubMedGoogle Scholar
  142. 142.
    Aitken RJ, Gordon E, Harkiss D, Twigg JP, Milne P, Jennings Z, et al. Relative impact of oxidative stress on the functional competence and genomic integrity of human spermatozoa. Biol Reprod. 1998;59:1037–46.PubMedGoogle Scholar
  143. 143.
    Piña-Guzmán B, Solís-Heredia MJ, Rojas-García AE, Urióstegui-Acosta M, Quintanilla-Vega B. Genetic damage caused by methyl-parathion in mouse spermatozoa is related to oxidative stress. Toxicol Appl Pharmacol. 2006;216:216–24.PubMedGoogle Scholar
  144. 144.
    Zubkova EV, Robaire B. Effects of ageing on ­spermatozoal chromatin and its sensitivity to in vivo and in vitro oxidative challenge in the Brown Norway rat. Hum Reprod. 2006;11:2901–10.Google Scholar
  145. 145.
    Heller C, Clermont Y. Kinetics of the germinal epithelium in man. Recent Prog Horm Res. 1964;20:545–75.PubMedGoogle Scholar
  146. 146.
    Sculze W, Salzbrunn A. Spatial and quantitative aspects of spermatogenetic tissue in primates. In: Neischlag E, Habenicht U, editors. Spermatogenesis-fertilization-contraception. Berlin: Springer; 1992. p. 267–83.Google Scholar
  147. 147.
    Rowe PJ, Comhaire F, Hargreave TB, Mellows HJ, editors. WHO manual for the standardized investigation and diagnosis of the infertile couple. Cambridge: Cambridge University Press; 1993.Google Scholar
  148. 148.
    Sharpe RM. Regulation of spermatogenesis. In: Knobill E, Neil JD, editors. The physiology of reproduction. New York: Raven; 1994. p. 1363–434.Google Scholar
  149. 149.
    De Kretser DM. Ultrastructural features of human spermiogenesis. Z Zellforsch Mikrosk Anat. 1969;98:477–505.PubMedGoogle Scholar
  150. 150.
    Hafez ES. The human semen and fertility regulation in the male. J Reprod Med. 1976;16:91–6.PubMedGoogle Scholar
  151. 151.
    Kruger TF, Menkveld R, Stander FS, Lombard CJ, Van der Merwe JP, van Zyl JA, et al. Sperm ­morphologic features as a prognostic factor in in vitro fertilization. Fertil Steril. 1986;46:1118–23.PubMedGoogle Scholar
  152. 152.
    Menkveld R, Stander FS, Kotze TJ, Kruger TF, van Zyl JA. The evaluation of morphological characteristics of human spermatozoa according to stricter ­criteria. Hum Reprod. 1990;5:586–92.PubMedGoogle Scholar
  153. 153.
    Katz DF, Overstreet JW, Samuels SJ, Niswander PW, Bloom TD, Lewis EL. Morphometric analysis of spermatozoa in the assessment of human male ­fertility. J Androl. 1986;7:203–10.PubMedGoogle Scholar
  154. 154.
    World Health Organization. World Health Orga­ni­zation laboratory manual for the examination of human semen and sperm-cervical mucus interaction. 4th ed. Cambridge: Cambridge University Press; 1999.Google Scholar
  155. 155.
    White IG. Mammalian sperm. In: Hafez ESE, editor. Reproduction of farm animals. Philadelphia: Lea & Febiger; 1974.Google Scholar
  156. 156.
    Jegou B. The Sertoli cell. Baillières Clin Endocrinol Metab. 1992;6:273–311.PubMedGoogle Scholar
  157. 157.
    Bellve AR, Zheng W. Growth factors as autocrine and paracrine modulators of male gonadal functions. J Reprod Fertil. 1989;85:771–93.PubMedGoogle Scholar
  158. 158.
    Sharpe T. Intratesticular control of steroidogenesis. Clin Endocrinol. 1990;33:787–807.Google Scholar
  159. 159.
    Sharpe RM. Monitoring of spermatogenesis in man-measurement of Sertoli cell- or germ cell-secreted proteins in semen or blood. Int J Androl. 1992;15:201–10.PubMedGoogle Scholar
  160. 160.
    Mahi-Brown CA, Yule TD, Tung KS. Evidence for active immunological regulation in prevention of testicular autoimmune disease independent of the blood-testis barrier. Am J Reprod Immunol Microbiol. 1988;16:165–70.PubMedGoogle Scholar
  161. 161.
    Barratt CL, Bolton AE, Cooke ID. Functional significance of white blood cells in the male and female reproductive tract. Hum Reprod. 1990;5:639–48.PubMedGoogle Scholar
  162. 162.
    Holstein AF, Schulze W, Breucker H. Histopathology of human testicular and epididymal tissue. In: Hargreave TB, editor. Male infertility. London: Springer; 1994. p. 105–48.Google Scholar
  163. 163.
    Nieschlag E, Behre H. Andrology. Male reproductive health and dysfunction. Berlin: Springer; 2001.Google Scholar
  164. 164.
    Tredway DR, Settlage DS, Nakamura RM, Motoshima M, Umezaki CU, Mishell Jr DR. Significance of timing for the postcoital evaluation of cervical mucus. Am J Obstet Gynecol. 1975;121:387–93.PubMedGoogle Scholar
  165. 165.
    Tredway DR, Buchanan GC, Drake TS. Comparison of the fractional postcoital test and semen analysis. Am J Obstet Gynecol. 1978;130:647–52.PubMedGoogle Scholar
  166. 166.
    Settlage DSF, Motoshima M, Tredway DR. Sperm transport from the external cervical os to the fallopian tubes in women: a time and quantitation study. In: Hafez ESE, Thibault CG, editors. Sperm transport, survival and fertilizing ability in vertebrates, vol. 26. Paris: INSERM; 1974. p. 201–17.Google Scholar
  167. 167.
    Eddy EM, O’Brien DA. The spermatozoon. In: Knobill EO, NO’Nneill JD, editors. The physiology of reproduction. New York: Raven; 1994.Google Scholar
  168. 168.
    Yanagamachi R. Mammalian fertilization. In: Knobill E, O’Brien NJ, editors. The physiology of reproduction. New York: Raven; 1994.Google Scholar
  169. 169.
    Mahanes MS, Ochs DL, Eng LA. Cell calcium of ejaculated rabbit spermatozoa before and following in vitro capacitation. Biochem Biophys Res Commun. 1986;134:664–70.PubMedGoogle Scholar
  170. 170.
    Thomas P, Meizel S. Phosphatidylinositol 4,5-­bisphosphate hydrolysis in human sperm stimulated with follicular fluid or progesterone is dependent upon Ca2+ influx. Biochem J. 1989;264:539–46.PubMedGoogle Scholar
  171. 171.
    Parks JE, Ehrenwalt E. Cholesterol efflux from mammalian sperm and its potential role in capacitation. In: Bavister BD, Cummins J, Raldon E, editors. Fertil­ization in mammals. Norwell: Serono Symposia; 1990.Google Scholar
  172. 172.
    Ravnik SE, Zarutskie PW, Muller CH. Purification and characterization of a human follicular fluid lipid transfer protein that stimulates human sperm capacitation. Biol Reprod. 1992;47:1126–33.PubMedGoogle Scholar
  173. 173.
    Benoff S, Cooper GW, Hurley I, Mandel FS, Rosenfeld DL. Antisperm antibody binding to human sperm inhibits capacitation induced changes in the levels of plasma membrane sterols. Am J Reprod Immunol. 1993;30:113–30.PubMedGoogle Scholar
  174. 174.
    Benoff S, Hurley I, Cooper GW, Mandel FS, Hershlag A, Scholl GM, et al. Fertilization potential in vitro is correlated with head-specific mannose-ligand receptor expression, acrosome status and membrane cholesterol content. Hum Reprod. 1993;8:2155–66.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Andrology Laboratory and Center for Reproductive MedicineGlickman Urological and Kidney Institute, OB-GYN and Women’s Health Institute, Cleveland ClinicClevelandUSA
  2. 2.Center for Reproductive MedicineGlickman Urological and Kidney Institute, OB-GYN and Women’s Health Institute, Cleveland ClinicClevelandUSA

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