Skip to main content
SpringerLink
Log in

Spermatogenesis: An Overview

  • Chapter
  • First Online:
Book cover Sperm Chromatin

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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Wilson JD. Syndromes of androgen resistance. Biol Reprod. 1992;46:168–73.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  4. Tishler PV. Diameter of testicles. N Engl J Med. 1971;285:1489.

    PubMed  CAS  Google Scholar 

  5. Winter JS, Faiman C. Pituitary-gonadal relations in male children and adolescents. Pediatr Res. 1972;6:126–35.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  7. Prader A. Testicular size: assessment and clinical importance. Triangle. 1966;7:240–3.

    PubMed  CAS  Google Scholar 

  8. Agger P. Scrotal and testicular temperature: its ­relation to sperm count before and after operation for varicocele. Fertil Steril. 1971;22:286–97.

    PubMed  CAS  Google Scholar 

  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. Christensen AK. Leydig cells. In: Hamilton DW, Greep RO, editors. Handbook of physiology. Baltimore: Williams and Wilkins; 1975. p. 57–94.

    Google Scholar 

  11. Kaler LW, Neaves WB. Attrition of the human Leydig cell population with advancing age. Anat Rec. 1978;192:513–8.

    PubMed  CAS  Google Scholar 

  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. 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.

    PubMed  CAS  Google Scholar 

  14. Glover TD, Barratt CLR, Tyler JJP, Hennessey JF. Human male fertility. London: Academic; 1980. p. 247.

    Google Scholar 

  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. Davidoff MS, Breucker H, Holstein AF, Seidel K. Cellular architecture of the lamina propria of human tubules. Cell Tissue Res. 1990;262:253–61.

    PubMed  CAS  Google Scholar 

  17. Roosen-Runge EC, Holstein A. The human rete testis. Cell Tissue Res. 1978;189:409–33.

    PubMed  CAS  Google Scholar 

  18. Russell LD, Griswold MD, editors. The Sertoli cell. Clearwater: Cache Press; 1993.

    Google Scholar 

  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.

    PubMed  Google Scholar 

  20. Behringer RR. The müllerian inhibitor and mammalian sexual development. Philos Trans R Soc Lond B Biol Sci. 1995;350:285–8.

    PubMed  CAS  Google Scholar 

  21. Josso N, di Clemente N, Gouédard L. Anti-Müllerian hormone and its receptors. Mol Cell Endocrinol. 2001;179:25–32.

    PubMed  CAS  Google Scholar 

  22. Clermont Y. Kinetics of spermatogenesis in mammals: seminiferous epithelium cycle and spermatogonial renewal. Physiol Rev. 1972;52:198–236.

    PubMed  CAS  Google Scholar 

  23. Clermont Y. The cycle of the seminiferous epithelium in man. Am J Anat. 1963;112:35–51.

    PubMed  CAS  Google Scholar 

  24. Schulze C. Morphological characteristics of the spermatogonial stem cells in man. Cell Tissue Res. 1974;198:191–9.

    Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  26. Huckins C. The spermatogonial stem cell population in adult rats. I. Their morphology, proliferation and maturation. Anat Rec. 1971;169:533–57.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  30. Gasse S. Studies on scaffold attachment sites and their relation to genome function. Int Rev Cytol. 1989;119:57.

    Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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. 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.

    PubMed  CAS  Google Scholar 

  34. Breucker H, Schäfer E, Holstein AF. Morphogenesis and fate of the residual body in human spermiogenesis. Cell Tissue Res. 1985;240:303–9.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  37. Schulze W, Rehder U. Organization and morphogenesis of the human seminiferous epithelium. Cell Tissue Res. 1984;237:395–407.

    PubMed  CAS  Google Scholar 

  38. Ward WS, Coffey DS. DNA packaging and organization in mammalian spermatozoa: comparison with somatic cells. Biol Reprod. 1991;44:569–74.

    PubMed  CAS  Google Scholar 

  39. McGhee JD, Felsenfeld G, Eisenberg H. Nucleosome structure and conformational changes. Biophys J. 1980;32:261–70.

    PubMed  CAS  Google Scholar 

  40. Sassone-Corsi P. Unique chromatin remodeling and transcriptional regulation in spermatogenesis. Science. 2002;296:2176–8.

    PubMed  CAS  Google Scholar 

  41. Dadoune JP, Siffroi JP, Alfonsi MF. Transcription in haploid male germ cells. Int Rev Cytol. 2004;237:1–56.

    PubMed  CAS  Google Scholar 

  42. Ward WS, Partin AW, Coffey DS. DNA loop domains in mammalian spermatozoa. Chromosoma. 1989;98:153–9.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  45. Lewis JD, Abbott DW, Ausió J. A haploid affair: core histone transitions during spermatogenesis. Biochem Cell Biol. 2003;81:131–40.

    PubMed  CAS  Google Scholar 

  46. Lewis JD, Song Y, de Jong ME, Bagha SM, Ausió J. A walk though vertebrate and invertebrate protamines. Chromosoma. 2003;111:473–82.

    PubMed  Google Scholar 

  47. Braun RE. Packaging paternal chromosomes with protamine. Nat Genet. 2001;28:10–2.

    PubMed  CAS  Google Scholar 

  48. Wu TF, Chu DS. Sperm chromatin: fertile grounds for proteomic discovery of clinical tools. Mol Cell Proteomics. 2008;7:1876–86.

    PubMed  CAS  Google Scholar 

  49. Ooi SL, Henikoff S. Germline histone dynamics and epigenetics. Curr Opin Cell Biol. 2007;19:257–65.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  53. Churikov D, Zalenskaya IA, Zalensky AO. Male germline-specific histones in mouse and man. Cytogenet Genome Res. 2004;105:203–14.

    PubMed  CAS  Google Scholar 

  54. Dadoune JP. The nuclear status of human sperm cells. Micron. 1995;26:323–45.

    PubMed  CAS  Google Scholar 

  55. Kierszenbaum AL. Transition nuclear proteins during spermiogenesis: unrepaired DNA breaks not allowed. Mol Reprod Dev. 2001;58:357–8.

    PubMed  CAS  Google Scholar 

  56. Lee CH, Cho YH. Aspects of mammalian spermatogenesis: electrophoretical analysis of protamines in mammalian species. Mol Cells. 1999;9:556–9.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  59. Laberge RM, Boissonneault G. On the nature and origin of DNA strand breaks in elongating spermatids. Biol Reprod. 2005;73:289–96.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  61. McPherson SM, Longo FJ. Nicking of rat spermatid and spermatozoa DNA: possible involvement of DNA topoisomerase II. Dev Biol. 1993;158:122–30.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  74. Caron N, Veilleux S, Boissonneault G. Stimulation of DNA repair by the spermatidal TP1 protein. Mol Reprod Dev. 2001;58:437–43.

    PubMed  CAS  Google Scholar 

  75. Brewer L, Corzett M, Balhorn R. Condensation of DNA by spermatid basic nuclear proteins. J Biol Chem. 2002;277:38895–900.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  Google Scholar 

  79. Balhorn R, Corzett M, Mazrimas JA. Formation of intraprotamine disulfides in vitro. Arch Biochem Biophys. 1992;296:384–93.

    PubMed  CAS  Google Scholar 

  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. Corzett M, Mazrimas J, Balhorn R. Protamine 1: protamine 2 stoichiometry in the sperm of eutherian mammals. Mol Reprod Dev. 2002;61:519–27.

    PubMed  CAS  Google Scholar 

  82. Fuentes-Mascorro G, Serrano H, Rosado A. Sperm chromatin. Arch Androl. 2000;45:215–25.

    PubMed  CAS  Google Scholar 

  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. Krawetz SA, Dixon GH. Sequence similarities of the protamine genes: implications for regulation and evolution. J Mol Evol. 1988;27:291–7.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  87. Loir M, Lanneau M. Structural function of the basic nuclear proteins in ram spermatids. J Ultrastruct Res. 1984;86:262–72.

    PubMed  CAS  Google Scholar 

  88. Singh J, Rao MR. Interaction of rat testis protein, TP, with nucleosome core particle. Biochem Int. 1988;17:701–10.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  Google Scholar 

  90. Szczygiel MA, Ward WS. Combination of dithiothreitol and detergent treatment of spermatozoa causes paternal chromosomal damage. Biol Reprod. 2002;67:1532–7.

    PubMed  CAS  Google Scholar 

  91. Hecht NB. Post-meiotic gene expression during spermatogenesis. Prog Clin Biol Res. 1988;267:291–313.

    PubMed  CAS  Google Scholar 

  92. Hecht NB. Regulation of ‘haploid expressed genes’ in male germ cells. J Reprod Fertil. 1990;88:679–93.

    PubMed  CAS  Google Scholar 

  93. Oliva R, Dixon GH. Vertebrate protamine gene evolution I. Sequence alignments and gene structure. J Mol Evol. 1990;30:333–46.

    PubMed  CAS  Google Scholar 

  94. Steger K. Transcriptional and translational regulation of gene expression in haploid spermatids. Anat Embryol (Berl). 1999;199:471–87.

    CAS  Google Scholar 

  95. Oliva R. Protamines and male infertility. Hum Reprod Update. 2006;12:417–35.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  97. Balhorn R, Reed S, Tanphaichitr N. Aberrant protamine 1/protamine 2 ratios in sperm of infertile human males. Experientia. 1988;44:52–5.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  99. Carrell DT, Emery BR, Hammoud S. Altered protamine expression and diminished spermatogenesis: what is the link? Hum Reprod Update. 2007;13:313–27.

    PubMed  CAS  Google Scholar 

  100. Kosower NS, Katayose H, Yanagimachi R. Thiol-disulfide status and acridine orange fluorescence of mammalian sperm nuclei. J Androl. 1992;13:342–8.

    PubMed  CAS  Google Scholar 

  101. Sakkas D, Mariethoz E, Manicardi G, et al. Origin of DNA damage in ejaculated human spermatozoa. Rev Reprod. 1999;4:31–7.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  105. Rousseaux S, Caron C, Govin J, Lestrat C, Faure AK, Khochbin S. Establishment of male-specific epigenetic information. Gene. 2005;345:139–53.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  108. Razin A, Riggs AD. DNA methylation and gene function. Science. 1980;210:604–10.

    PubMed  CAS  Google Scholar 

  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. 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.

    PubMed  CAS  Google Scholar 

  111. Rahe B, Erickson RP, Quinto M. Methylation of unique sequence DNA during spermatogenesis in mice. Nucleic Acids Res. 1983;11:7947–59.

    PubMed  CAS  Google Scholar 

  112. Trasler JM. Epigenetics in spermatogenesis. Mol Cell Endocrinol. 2009;306:33–6.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  Google Scholar 

  115. Ward WS. The structure of the sleeping genome: implications of sperm DNA organization for somatic cells. J Cell Biochem. 1994;55:77–82.

    PubMed  CAS  Google Scholar 

  116. Risley MS, Einheber S, Bumcrot DA. Changes in DNA topology during spermatogenesis. Chromosoma. 1986;94:217–27.

    PubMed  CAS  Google Scholar 

  117. Aitken RJ, De Iuliis GN. On the possible origins of DNA damage in human spermatozoa. Mol Hum Reprod. 2010;16:3–13.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  122. Kramer JA, Krawetz SA. Nuclear matrix interactions within the sperm genome. J Biol Chem. 1996;271:11619–22.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  134. Sinha Hikim AP, Swerdloff RS. Hormonal and genetic control of germ cell apoptosis in the testis. Rev Reprod. 1999;4:38–47.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  Google Scholar 

  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. Bauché F, Fouchard MH, Jégou B. Antioxidant system in rat testicular cells. FEBS Lett. 1994;349:392–6.

    PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  Google Scholar 

  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. Heller C, Clermont Y. Kinetics of the germinal epithelium in man. Recent Prog Horm Res. 1964;20:545–75.

    PubMed  CAS  Google Scholar 

  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. 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. 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. De Kretser DM. Ultrastructural features of human spermiogenesis. Z Zellforsch Mikrosk Anat. 1969;98:477–505.

    PubMed  Google Scholar 

  150. Hafez ES. The human semen and fertility regulation in the male. J Reprod Med. 1976;16:91–6.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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. White IG. Mammalian sperm. In: Hafez ESE, editor. Reproduction of farm animals. Philadelphia: Lea & Febiger; 1974.

    Google Scholar 

  156. Jegou B. The Sertoli cell. Baillières Clin Endocrinol Metab. 1992;6:273–311.

    PubMed  CAS  Google Scholar 

  157. Bellve AR, Zheng W. Growth factors as autocrine and paracrine modulators of male gonadal functions. J Reprod Fertil. 1989;85:771–93.

    PubMed  CAS  Google Scholar 

  158. Sharpe T. Intratesticular control of steroidogenesis. Clin Endocrinol. 1990;33:787–807.

    CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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. Nieschlag E, Behre H. Andrology. Male reproductive health and dysfunction. Berlin: Springer; 2001.

    Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  165. Tredway DR, Buchanan GC, Drake TS. Comparison of the fractional postcoital test and semen analysis. Am J Obstet Gynecol. 1978;130:647–52.

    PubMed  CAS  Google Scholar 

  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. 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. Yanagamachi R. Mammalian fertilization. In: Knobill E, O’Brien NJ, editors. The physiology of reproduction. New York: Raven; 1994.

    Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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. 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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Andrology Laboratory and Center for Reproductive Medicine, Glickman Urological and Kidney Institute, OB-GYN and Women’s Health Institute, Cleveland Clinic, Cleveland, OH, USA

    Rakesh Sharma PhD

  2. Center for Reproductive Medicine, Glickman Urological and Kidney Institute, OB-GYN and Women’s Health Institute, Cleveland Clinic, 9500 Euclid Avenue, Desk A19.1, Cleveland, OH, 44195, USA

    Ashok Agarwal PhD, HCLD (ABB) (Professor and Director)

Authors
  1. Rakesh Sharma PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ashok Agarwal PhD, HCLD (ABB)
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ashok Agarwal PhD, HCLD (ABB) .

Editor information

Editors and Affiliations

  1. St. Mary's Hospital, Div. Urology, McGill University, Lacombe Avenue 3830, Montreal, H3T 1M5, Québec, Canada

    Armand Zini

  2. Lerner College of Medicine, Center for Reproductive Medicine, Cleveland Clinic, Euclid Avenue 9500, Cleveland, 44195, Ohio, USA

    Ashok Agarwal

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Sharma, R., Agarwal, A. (2011). Spermatogenesis: An Overview. In: Zini, A., Agarwal, A. (eds) Sperm Chromatin. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6857-9_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-4419-6857-9_2

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4419-1781-2

  • Online ISBN: 978-1-4419-6857-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation