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Defective Spermatogenesis and Sperm DNA Damage

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Book cover A Clinician's Guide to Sperm DNA and Chromatin Damage

Abstract

Spermatogenesis is a highly complex temporal event during which relatively undifferentiated diploid cells called spermatogonia slowly evolve into highly specialized haploid cells called spermatozoa. The goal of spermatogenesis is to produce a genetically unique male gamete that can fertilize an ovum and produce offspring. Spermatogenesis is initiated through the neurological axis by the hypothalamus, which releases gonadotropin-releasing hormone (GnRH), which in turn signals follicle-stimulating hormone (FSH) and luteinizing hormone (LH) to be transmitted to the reproductive tract. 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 the seminiferous tubules undergo meiotic divisions to produce haploid secondary spermatocytes in the adluminal compartment in a process called spermatocytogenesis. After spermatocytogenesis, spermatids elongate to form spermatozoa by the process of spermiogenesis, a morphological development phase in which the nuclear transformations involving chromatin remodeling and compaction occur. Finally, spermatozoa are released from the Sertoli cells into the lumen of the seminiferous tubules in a process called spermiation and enter the epididymis for final maturation. Spermatogenesis in the human male takes about 74 days, while the process of epididymal maturation takes an additional 14 days. In the following sections, the complex transformation of the simple single diploid cell into a fully functional haploid cell is described. Furthermore, events associated with defective spermatogenesis and DNA fragmentation are highlighted, and mechanisms to repair DNA fragmentation are described in this chapter.

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References

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

    Article  CAS  PubMed  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 U S A. 1993;90:11162–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Smith EP, Boyd J, Frank GR, Takahashi H, Cohen RM, Specker B, Williams TC, Lubahn DB, Korach KS. Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N Engl J Med. 1994;331:1056–61.

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  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.

    Article  CAS  PubMed  Google Scholar 

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

    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.

    Article  CAS  PubMed  Google Scholar 

  9. de Kretser DM, Temple-Smith PD, Kerr JB. Anatomical and functional aspects of the male reproductive organs. In: Bandhauer K, Fricks JB, editors. Handbook of urology, vol. XVI. Berlin: Springer-Verlag; 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.

    Article  CAS  PubMed  Google Scholar 

  12. de Kretser DM, Kerr JB. The cytology of the testis. In: Knobill E, Neil JD, editors. The physiology of reproduction. New York: Raven Press; 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.

    CAS  PubMed  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.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  18. 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.

    Article  PubMed  Google Scholar 

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

    Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  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.

    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.

    Article  CAS  PubMed  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.

    Article  CAS  PubMed  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.

    Article  CAS  PubMed  PubMed Central  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.

    Article  CAS  PubMed  Google Scholar 

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

    Article  Google Scholar 

  31. Adachi Y, Kas E, Laemmli UK. Preferential cooperative binding of DNA topoisomerase II to scaffold-associated regions. EMBO J. 1989;13:3997.

    Google Scholar 

  32. Izaurralde E, Kas E, Laemmli UK. Highly preferential nucleation of histone H1 assembly on scaffold-associated regions. J Mol Biol. 1989;210:573–85.

    Article  CAS  PubMed  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.

    Article  CAS  PubMed  Google Scholar 

  34. Orthwein A, Fradet-Turcotte A, Noordermeer SM, Canny MD, Brun CM, Strecker J, Escribano-Diaz C, Durocher D. Mitosis inhibits DNA double-strand break repair to guard against telomere fusions. Science. 2015;344:189–93.

    Article  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  37. 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.

    Article  CAS  PubMed  Google Scholar 

  38. 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.

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  45. 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.

    CAS  PubMed  Google Scholar 

  46. Allen MJ, Lee C, Lee JD 4th, Pogany GC, Balooch M, Siekhaus WJ, Balhorn R. Atomic force microscopy of mammalian sperm chromatin. Chromosoma. 1993;102:623–30.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  52. Cho C, Willis WD, Goulding EH, Jung-Ha H, Choi YC, Hecht NB, Eddy EM. Haploinsufficiency of protamine-1 or -2 causes infertility in mice. Nat Genet. 2001;28:82–6.

    CAS  PubMed  Google Scholar 

  53. Yu YE, Zhang Y, Unni E, Shirley CR, Deng JM, Russell LD, Weil MM, Behringer RR, Meistrich ML. Abnormal spermatogenesis and reduced fertility in transition nuclear protein 1-deficient mice. Proc Natl Acad Sci U S A. 2000;97:4683–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Zhao M, Shirley CR, Yu YE, Mohapatra B, Zhang Y, Unni E, Deng JM, Arango NA, Terry NH, Weil MM, Russell LD, Behringer RR, Meistrich ML. Targeted disruption of the transition protein 2 gene affects sperm chromatin structure and reduces fertility in mice. Mol Cell Biol. 2001;21:7243–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  59. 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.

    Article  CAS  PubMed  Google Scholar 

  60. Gatewood JM, Cook GR, Balhorn R, Bradbury EM, Schmid CW. Sequence-specific packaging of DNA in human sperm chromatin. Science. 1987;236:962–4.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  62. 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.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  64. 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.

    Article  CAS  PubMed  Google Scholar 

  65. 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.

    Article  CAS  PubMed  Google Scholar 

  66. 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.

    CAS  PubMed  Google Scholar 

  67. 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.

    Article  CAS  PubMed  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.

    Article  CAS  PubMed  Google Scholar 

  69. 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.

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  71. 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.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  73. 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.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  75. Dixon GH, Aiken JM, Jankowski JM, McKenzie D, Moir R, States JC. 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 Publishing Corp; 1986.

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  78. Balhorn R, Cosman M, Thornton K, Krishnan VV, Corzett M, Bench G, Kramer C, Lee J, Hud NV, Allen MJ, et al. In: Gagnon C, editor. The male gamete: from basic science to clinical applications. Vienna: Cache River Press; 1999.

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  81. 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.

    Article  CAS  PubMed  Google Scholar 

  82. 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.

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  86. Cummins JM. Fertilization and elimination of the paternal mitochondrial genome. Hum Reprod. 2000;15:92–101.

    Article  PubMed  Google Scholar 

  87. Donnelly ET, O’Connell M, McClure N, Lewis SE. Differences in nuclear DNA fragmentation and mitochondrial integrity of semen and prepared human spermatozoa. Hum Reprod. 2000;15:1552–61.

    Article  CAS  PubMed  Google Scholar 

  88. Crow JF. The high spontaneous mutation rate: is it a health risk? ProcNat Acad Sci USA. 1997;94:8380–6.

    Article  CAS  Google Scholar 

  89. 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.

    Article  CAS  PubMed  Google Scholar 

  90. 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.

    Article  PubMed  Google Scholar 

  91. De Iuliis GN, Thomson LK, Mitchell LA, Finnie JM, Koppers AJ, Hedges A, Nixon B, Aitken RJ. 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.

    Article  PubMed  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  93. 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.

    Article  CAS  PubMed  Google Scholar 

  94. Casanueva FF, Villanueva L, Dieguez C, Diaz Y, Cabranes JA, Szoke B, Scanlon MF, Schally AV, Fernandez-Cruz A. Free fatty acids block growth hormone (GH) releasing hormone-stimulated GH secretion in man directly at the pituitary. J Clin Endocrinol Metab. 1987;65:634–42.

    Article  CAS  PubMed  Google Scholar 

  95. Nieschlag E, Leifke E. Empirical therapies for idiopathic infertility. In: Nieschlag E, Behre HM, editors. Andrology: male reproductive health and dysfunction, vol. 12. Heidelberg: Springer; 1997. p. 313–9.

    Chapter  Google Scholar 

  96. Ferlin A, Speltra E, Patassini C, Pati MA, Garolla A, Caretta N, Foresta C. Heat shock protein and heat shock factor expression in sperm: relation to oligozoospermia and varicocele. J Urol. 2010;183:1248–52.

    Article  CAS  PubMed  Google Scholar 

  97. Rendtorff R, Hohmann C, Reinmuth S, Müller A, Dittrich R, Beyer M, Wickmann L, Keil T, Henze G, Staudt BA. Hormone and sperm analyses after chemo- and radiotherapy in childhood and adolescence. Klin Padiatr. 2010;222:145–9.

    Article  CAS  PubMed  Google Scholar 

  98. Print CG, Loveland KL. Germ cell suicide: new insights into apoptosis during spermatogenesis. Bioassays. 2000;22:423–30.

    Article  CAS  Google Scholar 

  99. Martincic DS, Virant Klun I, Zorn B, Vrtovec HM. Germ cell apoptosis in the human testis. Pflugers Arch. 2001;442:59–60.

    Article  Google Scholar 

  100. Weng SL, Taylor SL, Morshedi M, Schuffner A, Duran EH, Beebe S, Oehninger S. Caspase activity and apoptotic markers in ejaculated human sperm. Mol Hum Reprod. 2002;8:984–91.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  102. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. 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.

    Article  PubMed  Google Scholar 

  104. Epstein J. Male genital system and urinary tract infection. In: Robbins Basic Pathology, editors. Kumar V, Abbas AK, Aster JC. Ninth Edition, Elsevier Saunders, PA; 2012. p. 651–680.

    Google Scholar 

  105. Martin SJ, Reutelingsperger CP, McGahon AJ, Rader JA, Van Schie RC, Laface DM, Green DR. Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl. J Exp Med. 1995;182:1545–56.

    Article  CAS  PubMed  Google Scholar 

  106. Sakkas D, Mariethoz E, St John JC. Abnormal sperm parameters in humans are indicative of an abortive apoptotic mechanism linked to the Fas-mediated pathway. Exp Cell Res. 1999b;251:350–5.

    Article  CAS  PubMed  Google Scholar 

  107. 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.

    Article  PubMed  Google Scholar 

  108. Grunewald S, Paasch U, Glander HJ, Anderegg U. Mature human spermatozoa do not transcribe novel RNA. Andrologia. 2005;37:69–71.

    Article  CAS  PubMed  Google Scholar 

  109. Meyer-Ficca ML, Lonchar J, Credidio C, Ihara M, Li Y, Wang ZQ, Meyer RG. Disruption of poly(ADP-ribose) homeostasis affects spermiogenesis and sperm chromatin integrity in mice. Biol Reprod. 2009;81:46–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. 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.

    Article  CAS  PubMed  Google Scholar 

  111. 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.

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  113. 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.

    Article  PubMed  CAS  Google Scholar 

  114. 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.

    Article  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  116. Sculze W, Salzbrunn A. Spatial and quantitative aspects of spermatogenetic tissue in primates. In: Neischlag E, Habenicht U, editors. Spermatogenesis-fertilization-contraception. Berlin: Springer, New York; 1992. p. 267–83.

    Chapter  Google Scholar 

  117. World Health Organization. WHO laboratory manual for the examination and processing of human semen. 5th ed. Geneva: WHO Press; 2010.

    Google Scholar 

  118. Sharpe RM. Regulation of spermatogenesis. In: Knobill E, Neil JD, editors. The physiology of reproduction. New York: Raven Press; 1994. p. 1363–434.

    Google Scholar 

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

    Article  PubMed  Google Scholar 

  120. Hoeijmakers JH. DNA damage, aging, and cancer. N Engl J Med. 2009;361:1475–85.

    Article  CAS  PubMed  Google Scholar 

  121. Gillet LC, Scharer OD. Molecular mechanisms of mammalian global genome nucleotide excision repair. Chem Rev. 2006;106:253–76.

    Article  CAS  PubMed  Google Scholar 

  122. Lyama T, Wilson DM. DNA repair mechanisms in dividing and non-dividing cells. DNA Repair (Amst). 2013;12:620–36.

    Article  CAS  Google Scholar 

  123. Boiteux S, Radicella JP. Base excision repair of 8-hydroxyguanine protects DNA from endogenous oxidative stress. Biochimie. 1999;81:59–67.

    Article  CAS  PubMed  Google Scholar 

  124. Aitken RJ, Smith TB, Jobling MS, Baker MA, De Iuliis GN. Oxidative stress and male reproductive health. Asian J Androl. 2014;16:31–8.

    Article  CAS  PubMed  Google Scholar 

  125. Shimura T, Inoue M, Taga M, Shiraishi K, Uematsu N, Takei N, Yuan ZM, Shinohara T, Niwa O. p53-dependent S-phase damage checkpoint and pronuclear cross talk in mouse zygotes with X-irradiated sperm. Mol Cell Biol. 2002;22:2220–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Champe PC, Harvey RA, Ferrier DR. DNA structure and replication. In: Lippincott’s illustrated reviews: biochemistry. 3rd ed. London: Lippincott Williams & Wilkins; 2005. p. 393–412.

    Google Scholar 

  127. Gordon FKE, Lamb DJ. DNA repair genes and genomic instability in severe male factor infertility. In: Carrell DT, editor. The genetics of male infertility. New York: Humana Press; 2006.

    Google Scholar 

  128. You Z, Bailis JM. DNA damage and decisions: CtIP coordinates DNA repair and cell cycle checkpoints. Trends Cell Biol. 2010;20:402–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Stracker TH, Petrini JH. The MRE11 complex: starting from the ends. Nat Rev Mol Cell Biol. 2011;12:90–103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Kohl KP, Sekelsky J. Meiotic and mitotic recombination in meiosis. Genetics. 2013;194:327–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Hou CC, Yang WX. New insights to the ubiquitin-proteasome pathway (UPP) mechanism during spermatogenesis. Mol Biol Rep. 2013;40:3213–30.

    Article  CAS  PubMed  Google Scholar 

  132. Koczorowska AM, Bialkowska A, Kluzek K, Zdzienicka MZ. The role of the Fanconi anemia pathway in DNA repair and maintenance of genome stability. Postepy Hig Med Dosw. 2014;68:459–72.

    Article  Google Scholar 

  133. Simhadri S, Peterson S, Patel D, Huo Y, Cai H, Bowman-Colin C, Miller S, Ludwig T, Ganesan S, Bhaumik M, Bunting S, Jasin M, Xia B. Male fertility defect associated with disrupted BRCA1-PALB2 interaction in mice. J Biol Chem. 2014;289:24617–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  136. Skinner MK. Cell-cell interactions in the testis. Endocr Rev. 1991;12:45–77.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  138. 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.

    Article  CAS  PubMed  Google Scholar 

  139. 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.

    Article  CAS  PubMed  Google Scholar 

  140. 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.

    Article  CAS  PubMed  Google Scholar 

  141. 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.

    Chapter  Google Scholar 

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

    Google Scholar 

  143. Eddy EM, O’Brien DA. The spermatozoon. In: Knobill EO, NO’Nneill JD, editors. The physiology of reproduction. New York: Raven Press; 1994.

    Google Scholar 

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

    Google Scholar 

  145. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. 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 

  147. 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.

    Article  CAS  PubMed  Google Scholar 

  148. 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.

    Article  CAS  PubMed  Google Scholar 

  149. 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.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA

    Rakesh Sharma

  2. American Center for Reproductive Medicine, Glickman Urological & Kidney Institute, Cleveland Clinic, Cleveland, OH, USA

    Ashok Agarwal

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  1. Rakesh Sharma
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  2. Ashok Agarwal
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Correspondence to Ashok Agarwal .

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Editors and Affiliations

  1. Department of Surgery, Division of Urology, McGill University, Montreal, Québec, Canada

    Armand Zini

  2. American Center for Reproductive Medicine, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio, USA

    Ashok Agarwal

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Sharma, R., Agarwal, A. (2018). Defective Spermatogenesis and Sperm DNA Damage. In: Zini, A., Agarwal, A. (eds) A Clinician's Guide to Sperm DNA and Chromatin Damage. Springer, Cham. https://doi.org/10.1007/978-3-319-71815-6_14

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