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Sperm Nucleoproteins (Histones and Protamines)

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A Clinician's Guide to Sperm DNA and Chromatin Damage

Abstract

Sperm nuclear architecture is unique, since sperm chromatin is packaged in many species by protamines, which are more basic and smaller than histones. The multistep procedure of histone exchange and its replacement by protamines during the late steps of spermatogenesis in mammals is a complex controlled process that requires the contribution of histone variants, histone posttranslational modifications (PTMs), transition proteins, remodeling machinery, and protamines. In the mature human sperm, while 85–95% of the mature sperm chromatin is bound to protamines, a small percentage of the chromatin (5–15%) remains bound to histones. An altered protamine ratio or an altered histone content or distribution in sperm indicates an abnormal chromatin packaging that can lead to male infertility through an increased susceptibility to DNA damage or abnormal epigenetic marking. However, little is known about how the differential distribution of genes in the sperm chromatin (nucleohistone and nucleoprotamine complexes) could impact in the early embryo development. It is suggested that histone variants and its PTMs and, perhaps, in conjunction with protamine PTMs, all together maintained in the mature sperm, could be involved in gene expression in early embryogenesis and transgenerational epigenetic inheritance.

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References

  1. Neto FTL, Bach PV, Najari BB, Li PS, Goldstein M. Spermatogenesis in humans and its affecting factors. Semin Cell Dev Biol. 2016;59:10–26.

    Article  PubMed  Google Scholar 

  2. Balhorn R. The protamine family of sperm nuclear proteins. Genome Biol. 2007;8:227.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Oliva R, Dixon GH. Vertebrate protamine genes and the histone-to-protamine replacement reaction. Prog Nucleic Acid Res Mol Biol. 1991;40:25–94.

    Article  CAS  PubMed  Google Scholar 

  4. Carrell DT, Aston KI, Oliva R, Emery BR, De Jonge CJ. The “omics” of human male infertility: integrating big data in a systems biology approach. Cell Tissue Res. 2016;363(1):295–312.

    Article  CAS  PubMed  Google Scholar 

  5. Rathke C, Baarends WM, Awe S, Renkawitz-Pohl R. Chromatin dynamics during spermiogenesis. Biochim Biophys Acta – Gene Regul Mech. 2014;1839(3):155–68.

    Article  CAS  Google Scholar 

  6. Youds JL, Boulton SJ. The choice in meiosis – defining the factors that influence crossover or non-crossover formation. J Cell Sci. 2011;124:501–13.

    Article  CAS  PubMed  Google Scholar 

  7. Kimmins S, Sassone-Corsi P. Chromatin remodelling and epigenetic features of germ cells. Nature. 2005;434:583–9.

    Article  CAS  PubMed  Google Scholar 

  8. Bao J, Bedford MT. Epigenetic regulation of the histone-to-protamine transition during spermiogenesis. Reproduction. 2016;151:R55–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Goudarzi A, Shiota H, Rousseaux S, Khochbin S. Genome-scale acetylation-dependent histone eviction during spermatogenesis. J Mol Biol. 2014;426(20):3342–9.

    Article  CAS  PubMed  Google Scholar 

  10. Meyer-Ficca ML, Lonchar JD, Ihara M, Meistrich ML, Austin CA, Meyer RG. Poly(ADP-ribose) polymerases PARP1 and PARP2 modulate topoisomerase II beta (TOP2B) function during chromatin condensation in mouse spermiogenesis. Biol Reprod. 2011;84:900–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Gawecka JE, Ribas-Maynou J, Benet J, Ward WS. A model for the control of DNA integrity by the sperm nuclear matrix. Asian J Androl. 2015;17:610–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. 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 

  13. Jones EL, Zalensky AO, Zalenskaya IA. Protamine withdrawal from human sperm nuclei following heterologous ICSI into hamster oocytes. Protein Pept Lett. 2011;18:811–6.

    Article  CAS  PubMed  Google Scholar 

  14. Carrell DT, Hammoud SS. The human sperm epigenome and its potential role in embryonic development. Mol Hum Reprod. 2010;16:37–47.

    Article  CAS  PubMed  Google Scholar 

  15. Vavouri T, Lehner B. Chromatin organization in sperm may be the major functional consequence of base composition variation in the human genome. PLoS Genet. 2011;7(4):e1002036.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Rando OJ. Daddy issues: paternal effects on phenotype. Cell. 2012;151(4):702–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Jodar M, Oliva R. Protamine alterations in human spermatozoa. Adv Exp Med Biol. 2014;791:83–102.

    Article  PubMed  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  19. Castillo J, Amaral A, Azpiazu R, Vavouri T, Estanyol JM, Ballescà JL, et al. Genomic and proteomic dissection and characterization of the human sperm chromatin. Mol Hum Reprod. 2014;20:1041–53.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  21. Björndahl L, Kvist U. Human sperm chromatin stabilization: a proposed model including zinc bridges. Mol Hum Reprod. 2010;16:23–9.

    Article  PubMed  CAS  Google Scholar 

  22. Balhorn R, Corzett M, Mazrimas J, Stanker LH, Wyrobek A. High-performance liquid chromatographic separation and partial characterization of human protamines 1, 2, and 3. Biotechnol Appl Biochem. 1987;9:82–8.

    CAS  PubMed  Google Scholar 

  23. Nelson JE, Krawetz SA. Mapping the clonally unstable recombinogenic PRM1–>PRM2–>TNP2 region of human 16p13.2. DNA Seq. 1995;5:163–8.

    Article  CAS  PubMed  Google Scholar 

  24. Chirat F, Arkhis A, Martinage A, Jaquinod M, Chevaillier P, Sautière P. Phosphorylation of human sperm protamines HP1 and HP2: identification of phosphorylation sites. Biochim Biophys Acta. 1993;1203:109–14.

    Article  CAS  PubMed  Google Scholar 

  25. Castillo J, Estanyol JM, Ballescá JL, Oliva R. Human sperm chromatin epigenetic potential: genomics, proteomics, and male infertility. Asian J Androl. 2015;17:601–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Brunner AM, Nanni P, Mansuy IM. Epigenetic marking of sperm by post-translational modification of histones and protamines. Epigenetics Chromatin. 2014;7:1–12.

    Google Scholar 

  27. Pruslin FH, Imesch E, Winston R, Rodman TC. Phosphorylation state of protamines 1 and 2 in human spermatids and spermatozoa. Gamete Res. 1987;18:179–90.

    Article  CAS  PubMed  Google Scholar 

  28. Papoutsopoulou S, Nikolakaki E, Chalepakis G, Kruft V, Chevaillier P, Giannakouros T. SR protein-specific kinase 1 is highly expressed in testis and phosphorylates protamine 1. Nucleic Acids Res. 1999;27:2972–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Pirhonen A. Identification of phosphoseryl residues in protamines from mature mammalian spermatozoa. Biol Reprod. 1994;50:981–6.

    Article  CAS  PubMed  Google Scholar 

  30. de Mateo S, Ramos L, de Boer P, Meistrich M, Oliva R. Protamine 2 precursors and processing. Protein Pept Lett. 2011;18:778–85.

    Article  PubMed  Google Scholar 

  31. Luense LJ, Wang X, Schon SB, Weller AH, Lin Shiao E, Bryant JM, et al. Comprehensive analysis of histone post-translational modifications in mouse and human male germ cells. Epigenetics Chromatin. 2016;9:24.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Brykczynska U, Hisano M, Erkek S, Ramos L, Oakeley EJ, Roloff TC, et al. Repressive and active histone methylation mark distinct promoters in human and mouse spermatozoa. Nat Struct Mol Biol. 2010;17:679–87.

    Article  CAS  PubMed  Google Scholar 

  33. Carrell DT, Hammoud SS. The human sperm epigenome and its potential role in embryonic development. Mol Hum Reprod. 2009;16:37–47.

    Article  PubMed  CAS  Google Scholar 

  34. van der Heijden GW, Ramos L, Baart EB, van den Berg IM, Derijck AA, van der Vlag J, et al. Sperm-derived histones contribute to zygotic chromatin in humans. BMC Dev Biol. 2008;8:34.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Nanassy L, Liu L, Griffin JT, Carrell D. The clinical utility of the protamine 1/protamine 2 ratio in sperm. Protein Pept Lett. 2011;18:772–7.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  37. 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 

  38. Simon L, Liu L, Murphy K, Ge S, Hotaling J, Aston KI, et al. Comparative analysis of three sperm DNA damage assays and sperm nuclear protein content in couples undergoing assisted reproduction treatment. Hum Reprod. 2014;29:904–17.

    Article  CAS  PubMed  Google Scholar 

  39. Hamad MF, Shelko N, Kartarius S, Montenarh M, Hammadeh ME. Impact of cigarette smoking on histone (H2B) to protamine ratio in human spermatozoa and its relation to sperm parameters. Andrology. 2014;2:666–77.

    Article  CAS  PubMed  Google Scholar 

  40. Aoki VW, Liu L, Jones KP, Hatasaka HH, Gibson M, Peterson CM, et al. Sperm protamine 1/protamine 2 ratios are related to in vitro fertilization pregnancy rates and predictive of fertilization ability. Fertil Steril. 2006;86:1408–15.

    Article  CAS  PubMed  Google Scholar 

  41. Torregrosa N, Domínguez-Fandos D, Camejo MI, Shirley CR, Meistrich ML, Ballescà JL, et al. Protamine 2 precursors, protamine 1/protamine 2 ratio, DNA integrity and other sperm parameters in infertile patients. Hum Reprod. 2006;21:2084–9.

    Article  CAS  PubMed  Google Scholar 

  42. Mengual L, Ballescà JL, Ascaso C, Oliva R. Marked differences in protamine content and P1/P2 ratios. J Androl. 2003;24:438–47.

    Article  PubMed  Google Scholar 

  43. Khara KK, Vlad M, Griffiths M, Kennedy CR. Human protamines and male infertility. J Assist Reprod Genet. 1997;14:282–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. de Yebra L, Ballescà JL, Vanrell JA, Bassas L, Oliva R. Complete selective absence of protamine P2 in humans. J Biol Chem. 1993;268:10553–7.

    PubMed  Google Scholar 

  45. de Mateo S, Gázquez C, Guimerà M, Balasch J, Meistrich ML, Ballescà JL, et al. Protamine 2 precursors (pre-P2), protamine 1 to protamine 2 ratio (P1/P2), and assisted reproduction outcome. Fertil Steril. 2009;91:715–22.

    Article  PubMed  CAS  Google Scholar 

  46. 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.

    CAS  PubMed  Google Scholar 

  47. Bach O, Glander HJ, Scholz G, Schwarz J. Electrophoretic patterns of spermatozoal nucleoproteins (NP) in fertile men and infertility patients and comparison with NP of somatic cells. Andrologia. 1990;22(3):217–24.

    Article  CAS  PubMed  Google Scholar 

  48. Lescoat D, Colleu D, Boujard D, Le Lannou D. Electrophoretic characteristics of nuclear proteins from human spermatozoa. Arch Androl. 1988;20:35–40.

    Article  CAS  PubMed  Google Scholar 

  49. Ribas-Maynou J, García-Peiró A, Martínez-Heredia J, Fernández-Encinas A, Abad C, Amengual MJ, et al. Nuclear degraded sperm subpopulation is affected by poor chromatin compaction and nuclease activity. Andrologia. 2015;47:286–94.

    Article  CAS  PubMed  Google Scholar 

  50. García-Peiró A, Martínez-Heredia J, Oliver-Bonet M, Abad C, Amengual MJ, Navarro J, et al. Protamine 1 to protamine 2 ratio correlates with dynamic aspects of DNA fragmentation in human sperm. Fertil Steril. 2011;95:105–9.

    Article  PubMed  CAS  Google Scholar 

  51. Castillo J, Simon L, de Mateo S, Lewis S, Oliva R. Protamine/DNA ratios and DNA damage in native and density gradient centrifuged sperm from infertile patients. J Androl. 2011;32:324–32.

    Article  CAS  PubMed  Google Scholar 

  52. Simon L, Castillo J, Oliva R, Lewis SEM. Relationships between human sperm protamines, DNA damage and assisted reproduction outcomes. Reprod BioMed Online. 2011;23:724–34.

    Article  CAS  PubMed  Google Scholar 

  53. 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.

    Article  CAS  PubMed  Google Scholar 

  54. Hammadeh ME, Hamad MF, Montenarh M, Fischer-Hammadeh C. Protamine contents and P1/P2 ratio in human spermatozoa from smokers and non-smokers. Hum Reprod. 2010;25:2708–20.

    Article  CAS  PubMed  Google Scholar 

  55. Nasr-Esfahani MH, Salehi M, Razavi S, Mardani M, Bahramian H, Steger K, et al. Effect of protamine-2 deficiency on ICSI outcome. Reprod BioMed Online. 2004;9:652–8.

    Article  CAS  PubMed  Google Scholar 

  56. Jodar M, Oriola J, Mestre G, Castillo J, Giwercman A, Vidal-Taboada JM, et al. Polymorphisms, haplotypes and mutations in the protamine 1 and 2 genes. Int J Androl. 2011;34:470–85.

    Article  CAS  PubMed  Google Scholar 

  57. Ni K, Spiess A-N, Schuppe H-C, Steger K. The impact of sperm protamine deficiency and sperm DNA damage on human male fertility: a systematic review and meta-analysis. Andrology. 2016;4:789–99.

    Article  CAS  PubMed  Google Scholar 

  58. Aoki VW. DNA integrity is compromised in protamine-deficient human sperm. J Androl. 2005;26:741–8.

    Article  CAS  PubMed  Google Scholar 

  59. Aoki VW, Liu L, Carrell DT. Identification and evaluation of a novel sperm protamine abnormality in a population of infertile males. Hum Reprod. 2005;20:1298–306.

    Article  CAS  PubMed  Google Scholar 

  60. Kouzarides T. Chromatin modifications and their function. Cell. 2007;128(4):693–705.

    Article  CAS  PubMed  Google Scholar 

  61. Ausió J. The shades of gray of the chromatin fiber. BioEssays. 2015;37:46–51.

    Article  PubMed  CAS  Google Scholar 

  62. Govin J, Caron C, Lestrat C, Rousseaux S, Khochbin S. The role of histones in chromatin remodelling during mammalian spermiogenesis. Eur J Biochem. 2004;271:3459–69.

    Article  CAS  PubMed  Google Scholar 

  63. Rajender S, Avery K, Agarwal A. Epigenetics, spermatogenesis and male infertility. Mutat Res. 2011;727:62–71.

    Article  CAS  PubMed  Google Scholar 

  64. Lin Q, Sirotkin A, Skoultchi AI. Normal spermatogenesis in mice lacking the testis-specific linker histone H1t. Mol Cell Biol. 2000;20:2122–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Fantz DA, Hatfield WR, Horvath G, Kistler MK, Kistler WS. Mice with a targeted disruption of the H1t gene are fertile and undergo normal changes in structural chromosomal proteins during spermiogenesis. Biol Reprod. 2001;64:425–31.

    Article  CAS  PubMed  Google Scholar 

  66. Martianov I, Brancorsini S, Catena R, Gansmuller A, Kotaja N, Parvinen M, et al. Polar nuclear localization of H1T2, a histone H1 variant, required for spermatid elongation and DNA condensation during spermiogenesis. Proc Natl Acad Sci. 2005;102:2808–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Tanaka H, Iguchi N, Isotani A, Kitamura K, Toyama Y, Matsuoka Y, et al. HANP1/H1T2, a novel histone H1-like protein involved in nuclear formation and sperm fertility. Mol Cell Biol. 2005;25:7107–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Fan Y, Sirotkin A, Russell RG, Ayala J, Skoultchi AI. Individual somatic H1 subtypes are dispensable for mouse development even in mice lacking the H10 replacement subtype. Mol Cell Biol. 2001;21:7933–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Changolkar LN, Costanzi C, Leu NA, Chen D, McLaughlin KJ, Pehrson JR. Developmental changes in histone macroH2A1-mediated gene regulation. Mol Cell Biol. 2007;27:2758–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Boulard M, Storck S, Cong R, Pinto R, Delage H, Bouvet P, et al. Histone variant macroH2A1 deletion in mice causes female-specific steatosis. Epigenetics Chromatin. 2010;3:8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Celeste A, Petersen S, Romanienko PJ, Fernandez-Capetillo O, Chen HT, Sedelnikova OA, et al. Genomic instability in mice lacking histone H2AX. Science. 2002;296:922–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Faast R, Thonglairoam V, Schulz TC, Beall J, Wells JR, Taylor H, et al. Histone variant H2A.Z is required for early mammalian development. Curr Biol. 2001;11:1183–7.

    Article  CAS  PubMed  Google Scholar 

  73. Santoro SW, Dulac C, Banaszynski L, Allis C, Lewis P, Barski A, et al. The activity-dependent histone variant H2BE modulates the life span of olfactory neurons. Elife. 2012;1:662–74.

    Article  CAS  Google Scholar 

  74. Tang MCW, Jacobs SA, Wong LH, Mann JR. Conditional allelic replacement applied to genes encoding the histone variant H3.3 in the mouse. Genesis. 2013;51:142–6.

    Article  CAS  PubMed  Google Scholar 

  75. Howman EV, Fowler KJ, Newson AJ, Redward S, MacDonald AC, Kalitsis P, et al. Early disruption of centromeric chromatin organization in centromere protein A (Cenpa) null mice. Proc Natl Acad Sci. 2000;97:1148–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Kalitsis P, Fowler KJ, Earle E, Griffiths B, Howman E, Newson AJ, et al. Partially functional Cenpa–GFP fusion protein causes increased chromosome missegregation and apoptosis during mouse embryogenesis. Chromosom Res. 2003;11:345–57.

    Article  CAS  Google Scholar 

  77. Maze I, Noh K-M, Soshnev AA, Allis CD. Every amino acid matters: essential contributions of histone variants to mammalian development and disease. Nat Rev Genet. 2014;15:259–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Banaszynski LA, Allis CD, Lewis PW. Histone variants in metazoan development. Dev Cell. 2010;19:662–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Peterson CL, Laniel M-A. Histones and histone modifications. Curr Biol. 2004;14(14):R546–51.

    Article  CAS  PubMed  Google Scholar 

  80. Oliva R, Mezquita C. Histone H4 hyperacetylation and rapid turnover of its acetyl groups in transcriptionally inactive rooster testis spermatids. Nucleic Acids Res. 1982;10:8049–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Sonnack V, Failing K, Bergmann M, Steger K. Expression of hyperacetylated histone H4 during normal and impaired human spermatogenesis. Andrologia. 2002;34:384–90.

    Article  CAS  PubMed  Google Scholar 

  82. Govin J, Escoffier E, Rousseaux S, Kuhn L, Ferro M, Thévenon J, et al. Pericentric heterochromatin reprogramming by new histone variants during mouse spermiogenesis. J Cell Biol. 2007;176:283–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Oliva R, Bazett-Jones D, Mezquita C, Dixon GH. Factors affecting nucleosome disassembly by protamines in vitro. Histone hyperacetylation and chromatin structure, time dependence, and the size of the sperm nuclear proteins. J Biol Chem. 1987;262:17016–25.

    CAS  PubMed  Google Scholar 

  84. Hazzouri M, Pivot-Pajot C, Faure AK, Usson Y, Pelletier R, Sèle B, et al. Regulated hyperacetylation of core histones during mouse spermatogenesis: involvement of histone deacetylases. Eur J Cell Biol. 2000;79:950–60.

    Article  CAS  PubMed  Google Scholar 

  85. Faure AK, Pivot-Pajot C, Kerjean A, Hazzouri M, Pelletier R, Péoc'h M, et al. Misregulation of histone acetylation in Sertoli cell-only syndrome and testicular cancer. Mol Hum Reprod. 2003;9:757–63.

    Article  CAS  PubMed  Google Scholar 

  86. Godmann M, Auger V, Ferraroni-Aguiar V, Di Sauro A, Sette C, Behr R, et al. Dynamic regulation of histone H3 methylation at lysine 4 in mammalian spermatogenesis. Biol Reprod. 2007;77(5):754–64.

    Article  CAS  PubMed  Google Scholar 

  87. Glaser S, Lubitz S, Loveland KL, Ohbo K, Robb L, Schwenk F, et al. The histone 3 lysine 4 methyltransferase, Mll2, is only required briefly in development and spermatogenesis. Epigenetics Chromatin. 2009;2:5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. Payne C, Braun RE. Histone lysine trimethylation exhibits a distinct perinuclear distribution in Plzf-expressing spermatogonia. Dev Biol. 2006;293:461–72.

    Article  CAS  PubMed  Google Scholar 

  89. Hammoud SS, Nix DA, Zhang H, Purwar J, Carrell DT, Cairns BR. Distinctive chromatin in human sperm packages genes for embryo development. Nature. 2009;460:473–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Krejčí J, Stixová L, Pagáčová E, Legartová S, Kozubek S, Lochmanová G, et al. Post-translational modifications of histones in human sperm. J Cell Biochem. 2015;116:2195–209.

    Article  PubMed  CAS  Google Scholar 

  91. Siklenka K, Erkek S, Godmann M, Lambrot R, McGraw S, Lafleur C, et al. Disruption of histone methylation in developing sperm impairs offspring health transgenerationally. Science. 2015;350(6261):aab2006.

    Article  PubMed  CAS  Google Scholar 

  92. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Samans B, Yang Y, Krebs S, Sarode GV, Blum H, Reichenbach M, et al. Uniformity of nucleosome preservation pattern in mammalian sperm and its connection to repetitive DNA elements. Dev Cell. 2014;30:23–35.

    Article  CAS  PubMed  Google Scholar 

  94. Royo H, Stadler MB, Peters AHFM, Arpanahi A, Brinkworth M, Iles D, et al. Alternative computational analysis shows no evidence for nucleosome enrichment at repetitive sequences in mammalian spermatozoa. Dev Cell Elsevier. 2016;37:98–104.

    Article  CAS  Google Scholar 

  95. Zhong HZ, Lv FT, Deng XL, Hu Y, Xie DN, Lin B, et al. Evaluating γh2AX in spermatozoa from male infertility patients. Fertil Steril. 2015;104:574–81.

    Article  CAS  PubMed  Google Scholar 

  96. Zhang X, Gabriel MS, Zini A. Sperm nuclear histone to protamine ratio in fertile and infertile men: evidence of heterogeneous subpopulations of spermatozoa in the ejaculate. J Androl. 2006;27:414–20.

    Article  PubMed  CAS  Google Scholar 

  97. 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.

    Article  PubMed  Google Scholar 

  98. Zini A, Zhang X, Gabriel MS. Sperm nuclear histone H2B: correlation with sperm DNA denaturation and DNA stainability. Asian J Androl. 2008;10:865–71.

    Article  PubMed  Google Scholar 

  99. 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.

    Article  CAS  PubMed  Google Scholar 

  100. Hammoud SS, Nix DA, Hammoud AO, Gibson M, Cairns BR, Carrell DT. Genome-wide analysis identifies changes in histone retention and epigenetic modifications at developmental and imprinted gene loci in the sperm of infertile men. Hum Reprod. 2011;26:2558–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Azpiazu R, Amaral A, Castillo J, Estanyol JM, Guimerà M, Ballescà JL, et al. High-throughput sperm differential proteomics suggests that epigenetic alterations contribute to failed assisted reproduction. Hum Reprod. 2014;29:1225–37.

    Article  CAS  PubMed  Google Scholar 

  102. de Mateo S, Castillo J, Estanyol JM, Ballescà JL, Oliva R. Proteomic characterization of the human sperm nucleus. Proteomics. 2011;11:2714–26.

    Article  PubMed  CAS  Google Scholar 

  103. Baker MA, Naumovski N, Hetherington L, Weinberg A, Velkov T, Aitken RJ. Head and flagella subcompartmental proteomic analysis of human spermatozoa. Proteomics. 2013;13:61–74.

    Article  CAS  PubMed  Google Scholar 

  104. Castillo J, Amaral A, Oliva R. Sperm nuclear proteome and its epigenetic potential. Andrology. 2014;2:326–38.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

Supported by grants to RO from the Spanish Ministry of Economy and Competitiveness (Ministerio de Economía y Competividad; Instituto de Salut Carlos III, Fondos FEDER, “una manera de hacer Europa,” PI13/00699, P16/00346, CP11/00312, BFU2011–29739), EUGIN-UB Research Excellence Program (EU-REP 2014), Fundación Salud 2000 (SERONO 13–015), and EU-FP7-PEOPLE-2011-ITN289880. FB is granted by the Spanish Ministry of Education, Culture and Sports (Ministerio de Educación, Cultura y Deporte para la Formación de Profesorado Universitario, FPU15). MJ is granted by the Government of Catalonia (Generalitat de Catalunya, pla estratègic de recerca i innovació en salut, PERIS 2016–2020).

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  1. Molecular Biology of Reproduction and Development Research Group, Department of Biomedicine, Faculty of Medicine, and Biochemistry and Molecular Genetics Service, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, and Hospital Clínic, Casanova 143, 08036, Barcelona, Spain

    Ferran Barrachina, Ada Soler-Ventura, Rafael Oliva & Meritxell Jodar

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  4. Meritxell Jodar
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Correspondence to Rafael Oliva or Meritxell Jodar .

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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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Barrachina, F., Soler-Ventura, A., Oliva, R., Jodar, M. (2018). Sperm Nucleoproteins (Histones and Protamines). 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_2

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  • DOI: https://doi.org/10.1007/978-3-319-71815-6_2

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  • Print ISBN: 978-3-319-71814-9

  • Online ISBN: 978-3-319-71815-6

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