Abstract
Chromosomes in the human sperm nucleus adopt a hierarchy of structures starting from protamine toroids, the elementary units of DNA packaging, and up to the higher-order organization of chromosome territories. Nonrandom intranuclear positioning of individual chromosomes, with centromeres aggregated in the internally located chromocenter and preferential location of telomeres at the nuclear periphery, suggests a highly defined architecture of the sperm nucleus at the level of genome. Such an ordered chromatin organization in the sperm nucleus may have a functional significance and determine the onset of paternal gene activity at early stages of embryonic development. This chapter describes relevant experimental data with primary attention to studies of human spermatozoa and discusses the implications of sperm chromosome organization for male reproductive health.
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Abbreviations
- CHR:
-
Chromosome
- CT:
-
Chromosome territory
- FISH:
-
Fluorescence in situ hybridization
- ICSI:
-
Intracytoplasmic sperm injection
- MSCI:
-
Meiotic sex chromosome inactivation
- MSUC:
-
Meiotic silencing of unsynapsed chromatin
- WCP:
-
Whole chromosome painting probe
References
Ajduk A, Yamauchi Y, Ward MA (2006) Sperm chromatin remodeling after intracytoplasmic sperm injection differs from that of in vitro fertilization. Biol Reprod 75:442–451
Allen MJ, Bradbury EM, Balhorn R (1996) The chromatin structure of well-spread demembranated human sperm nuclei revealed by atomic force microscopy. Scanning Microsc 10:989–994
Arpanahi A, Brinkworth M, Iles D, Krawetz SA, Paradowska A, Platts AE, Saida M, Steger K, Tedder P, Miller D (2009) Endonuclease-sensitive regions of human spermatozoal chromatin are highly enriched in promoter and CTCF binding sequences. Genome Res 19:1338–1349
Baarends WM, Wassenaar E, Hoogerbrugge JW, Schoenmakers S, Sun ZW, Grootegoed JA (2007) Increased phosphorylation and dimethylation of XY body histones in the Hr6b-knockout mouse is associated with derepression of the X chromosome. J Cell Sci 120:1841–1851
Balhorn R (1982) A model for the structure of chromatin in mammalian sperm. J Cell Biol 93:298–305
Balhorn R (2007) The protamine family of sperm nuclear proteins. Genome Biol 8:227
Banerjee S, Smallwood A (1995) A chromatin model of IGF2/H19 imprinting. Nat Genet 11:237–238
Bickmore WA, Chubb JR (2003) Dispatch. Chromosome position: now, where was I? Curr Biol 13:R357–R359
Bonduelle M, Aytoz A, Van Assche E, Devroey P, Liebaers I, Van Steirteghem A (1998) Incidence of chromosomal aberrations in children born after assisted reproduction through intracytoplasmic sperm injection. Hum Reprod 13:781–782
Borden J, Manuelidis L (1988) Movement of the X chromosome in epilepsy. Science 242:1687–1691
Breed WG (1994) How does sperm meet egg?—in a marsupial. Reprod Fertil Dev 6:485–506
Brewer LR, Corzett M, Balhorn R (1999) Protamine-induced condensation and decondensation of the same DNA molecule. Science 286:120–123
Brykczynska U, Hisano M, Erkek S, Ramos L, Oakeley EJ, Roloff TC, Beisel C, Schübeler D, Stadler MB, Peters A (2010) Repressive and active histone methylation mark distinct promoters in human and mouse spermatozoa. Nat Struct Mol Biol 17:679–687
Carrell DT, Hammoud SS (2010) The human sperm epigenome and its potential role in embryonic development. Mol Hum Reprod 16:37–47
Chow JC, Heard E (2010) Nuclear organization and dosage compensation. Cold Spring Harb Perspect Biol 2:a000604
Churikov D, Zalenskaya IA, Zalensky AO (2004) Male germline-specific histones in mouse and man. Cytogenet Genome Res 105:203–214
Cremer T, Cremer C (2001) Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nat Rev Genet 2:292–301
Croft JA, Bridger JM, Boyle S, Perry P, Teague P, Bickmore WA (1999) Differences in the localization and morphology of chromosomes in the human nucleus. J Cell Biol 145:1119–1131
Dolnik AV, Pochukalina GN, Parfenov VN, Karpushev AV, Podgornaya OI, Voronin AP (2007) Dynamics of satellite binding protein CENP-B and telomere binding protein TRF2/MTBP in the nuclei of mouse spermatogenic line. Cell Biol Int 31:316–329
Finch KA, Fonseka KG, Abogrein A, Ioannou D, Handyside AH, Thornhill AR, Hickson N, Griffin DK (2008) Nuclear organization in human sperm: preliminary evidence for altered sex chromosome centromere position in infertile males. Hum Reprod 23:1263–1270
Foster HA, Abeydeera LR, Griffin DK, Bridger JM (2005) Non-random chromosome positioning in mammalian sperm nuclei, with migration of the sex chromosomes during late spermatogenesis. J Cell Sci 118:1811–1820
Fundele RH, Surani MA (1994) Experimental embryological analysis of genetic imprinting in mouse development. Dev Genet 15:515–522
Garagna S, Zuccotti M, Thornhill A, Fernandez-Donoso R, Berrios S, Capanna E, Redi CA (2001) Alteration of nuclear architecture in male germ cells of chromosomally derived subfertile mice. J Cell Sci 114:4429–4434
Gardiner-Garden M, Ballesteros M, Gordon M, Tam PP (1998) Histone- and protamine-DNA association: conservation of different patterns within the beta-globin domain in human sperm. Mol Cell Biol 18:3350–3356
Gatewood JM, Cook GR, Balhorn R, Bradbury EM, Schmid CW (1987) Sequence-specific packaging of DNA in human sperm chromatin. Science 236:962–964
Gatewood JM, Cook GR, Balhorn R, Schmid CW, Bradbury EM (1990) Isolation of four core histones from human sperm chromatin representing a minor subset of somatic histones. J Biol Chem 265:20662–20666
Geraedts JP, Pearson PL (1975) Spatial distribution of chromosomes 1 and Y in human spermatozoa. J Reprod Fertil 45:515–517
Gineitis AA, Zalenskaya IA, Yau PM, Bradbury EM, Zalensky AO (2000) Human sperm telomere-binding complex involves histone H2B and secures telomere membrane attachment. J Cell Biol 151:1591–1598
Greaves IK, Svartman M, Wakefield M, Taggart D, De Leo A, Ferguson-Smith MA, Rens W, O’Brien PC, Voullaire L, Westerman M, Graves JA (2001) Chromosomal painting detects non-random chromosome arrangement in dasyurid marsupial sperm. Chromosome Res 9:251–259
Greaves IK, Rens W, Ferguson-Smith MA, Griffin D, Marshall Graves JA (2003) Conservation of chromosome arrangement and position of the X in mammalian sperm suggests functional significance. Chromosome Res 11:503–512
Gurevitch M, Amiel A, Ben-Zion M, Fejgin M, Bartoov B (2001) Acrocentric centromere organization within the chromocenter of the human sperm nucleus. Mol Reprod Dev 60:507–516
Haaf T, Ward DC (1995) Higher order nuclear structure in mammalian sperm revealed by in situ hybridization and extended chromatin fibers. Exp Cell Res 219:604–611
Hammadeh ME, Hamad MF, Montenarh M, Fischer-Hammadeh C (2010) Protamine contents and P1/P2 ratio in human spermatozoa from smokers and non-smokers. Hum Reprod 25:2708–2720
Hammoud SS, Nix DA, Zhang H, Purwar J, Carrell DT, Cairns BR (2009) Distinctive chromatin in human sperm packages genes for embryo development. Nature (Lond) 460:473–478
Hammoud SS, Purwar J, Pflueger C, Cairns BR, Carrell DT (2010) Alterations in sperm DNA methylation patterns at imprinted loci in two classes of infertility. Fertil Steril 94:1728–1733
Handel MA (2004) The XY body: a specialized meiotic chromatin domain. Exp Cell Res 296:57–63
Hazzouri M, Rousseaux S, Mongelard F, Usson Y, Pelletier R, Faure AK, Vourc’h C, Sèle B (2000) Genome organization in the human sperm nucleus studied by FISH and confocal microscopy. Mol Reprod Dev 55:307–315
Hewitson L, Dominko T, Takahashi D, Martinovich C, Ramalho-Santos J, Sutovsky P, Fanton J, Jacob D, Monteith D, Neuringer M, Battaglia D, Simerly C, Schatten G (1999) Unique checkpoints during the first cell cycle of fertilization after intracytoplasmic sperm injection in rhesus monkeys. Nat Med 5:431–433
Hoyer-Fender S (2003) Molecular aspects of XY body formation. Cytogenet Genome Res 103:245–255
Hoyer-Fender S, Singh PB, Motzkus D (2000) The murine heterochromatin protein M31 is associated with the chromocenter in round spermatids and is a component of mature spermatozoa. Exp Cell Res 254:72–79
Hud NV, Allen MJ, Downing KH, Lee J, Balhorn R (1993) Identification of the elemental packing unit of DNA in mammalian sperm cells by atomic force microscopy. Biochem Biophys Res Commun 193:1347–1354
In’t Veld P, Brandenburg H, Verhoeff A, Dhont M, Los F (1995) Sex chromosomal abnormalities and intracytoplasmic sperm injection. Lancet 346:773
Iwarsson E, Malmgren H, Inzunza J, Ahrlund-Richter L, Sjoblom P, Rosenlund B, Fridtrom M, Hovatta O, Nordenskjold M, Blennow E (2000) Highly abnormal cleavage divisions in preimplantation embryo from translocations carriers. Prenat Diagn 20:1038–1047
Johnson GD, Lalancette C, Linnemann AK, Leduc F, Boissonneault G, Krawetz SA (2011) The sperm nucleus: chromatin, RNA, and the nuclear matrix. Reproduction 141:21–36
Jones EL, Mudrak O, Zalensky AO (2010) Kinetics of human male pronuclear development in a heterologous ICSI model. J Assist Reprod Genet 27:277–283
Joshi NV, Medina H, Colasante C, Osuna A (2000) Ultrastructural investigation of human sperm using atomic force microscopy. Arch Androl 44:51–57
Katayama M, Koshida M, Miyake M (2002) Fate of the acrosome in ooplasm in pigs after IVF and ICSI. Hum Reprod 17:2657–2664
Kingsley K, Wirth J, van der Maarel S, Freier S, Ropers HH, Haaf T (1997) Complex FISH probes for the subtelomeric regions of all human chromosomes: comparative hybridization of CEPH YACs to chromosomes of the Old World monkey Presbytis cristata and great apes. Cytogenet Cell Genet 78:12–19
Knight SJ, Flint J (2000) Perfect endings: a review of subtelomeric probes and their use in clinical diagnosis. J Med Genet 37:401–409
Knight SJ, Horsley SW, Regan R, Lawrie NM, Maher EJ, Cardy DL, Flint J, Kearney L (1997) Development and clinical application of an innovative fluorescence in situ hybridization technique which detects submicroscopic rearrangements involving telomeres. Eur J Hum Genet 5:1–8
Lanctôt C, Cheutin T, Cremer M, Cavalli G, Cremer T (2007) Dynamic genome architecture in the nuclear space: regulation of gene expression in three dimensions. Nat Rev Genet 8:104–115
Lee JT (2010) The X as model for RNA’s niche in epigenomic regulation. Cold Spring Harb Perspect Biol 2:a003749
Leitch AR (2000) Higher levels of organization in the interphase nucleus of cycling and differentiated cells. Microbiol Mol Biol Rev 64:138–152
Li Z, Yang J, Huang H (2006) Oxidative stress induces H2AX phosphorylation in human spermatozoa. FEBS Lett 580:6161–6168
Liebaers I, Bonduelle M, Van Assche E, Devroey P, Van Steirteghem A (1995) Sex chromosome abnormalities after intracytoplasmic sperm injection. Lancet 346:1095
Luetjens CM, Payne C, Schatten G (1999) Non-random chromosome positioning in human sperm and sex chromosome anomalies following intracytoplasmic sperm injection. Lancet 353:1240
Mahadevaiah SK, Turner JM, Baudat F, Rogakou EP, de Boer P, Blanco-Rodriguez J, Jasin M, Keeney S, Bonner WM, Burgoyne PS (2001) Recombinational DNA double-strand breaks in mice precede synapsis. Nat Genet 27:271–276
Manvelyan M, Hunstig F, Bhatt S, Mrasek K, Pellestor F, Weise A, Simonyan I, Aroutiounian R, Liehr T (2008) Chromosome distribution in human sperm—a 3D multicolor banding-study. Mol Cytogenet 1:25
Mayer W, Smith A, Fundele R, Haaf T (2000) Spatial separation of parental genomes in preimplantation mouse embryos. J Cell Biol 148:629–634
McCarrey JR, Watson C, Atencio J, Ostermeier GC, Marahrens Y, Jaenisch R, Krawetz SA (2002) X-chromosome inactivation during spermatogenesis is regulated by an Xist/Tsix-independent mechanism in the mouse. Genesis 34:257–266
Meaburn KJ, Levy N, Toniolo D, Bridger JM (2005) Chromosome positioning is largely unaffected in lymphoblastoid cell lines containing emerin or A-type lamin mutations. Biochem Soc Trans 33:1438–1440
Meister P, Mango SE, Gasser SM (2011) Locking the genome: nuclear organization and cell fate. Curr Opin Genet Dev 21:167–174
Meistrich ML, Mohapatra B, Shirley CR, Zhao M (2003) Roles of transition nuclear proteins in spermiogenesis. Chromosoma (Berl) 111:483–488
Meyer-Ficca M, Muller-Navia J, Scherthan H (1998) Clustering of pericentromeres initiates in step 9 of spermiogenesis of the rat (Rattus norvegicus) and contributes to a well defined genome architecture in the sperm nucleus. J Cell Sci 111:1363–1370
Miller D, Brinkworth M, Iles D (2010) Paternal DNA packaging in spermatozoa: more than the sum of its parts? DNA, histones, protamines and epigenetics. Reproduction 139:287–301
Misteli T (2004) Spatial positioning: a new dimension in genome function. Cell 119:153–156
Misteli T (2007) Beyond the sequence: cellular organization of genome function. Cell 128:787–800
Mudrak OS, Nazarov IB, Jones EL, Zalensky AO (2012) Positioning of chromosomes in human spermatozoa is determined by ordered centromere arrangement. PLoS ONE 7: e52944
Mudrak O, Tomilin N, Zalensky A (2005) Chromosome architecture in the decondensing human sperm nucleus. J Cell Sci 118:4541–4550
Mudrak O, Zalenskaya I, Zalensky O (2011) Organization of chromosomes during spermatogenesis and in mature sperm. In: Rousseaux S, Khochbin S (eds) Epigenetics and human reproduction, 1st edn. Springer, Berlin
Nagele RG, Freeman T, McMorrow L, Thomson Z, Kitson-Wind K, Lee H (1999) Chromosomes exhibit preferential positioning in nuclei of quiescent human cells. J Cell Sci 112:525–535
Namekawa SH, Park PJ, Zhang LF, Shima JE, McCarrey JR, Griswold MD, Lee JT (2006) Postmeiotic sex chromatin in the male germline of mice. Curr Biol 16:660–667
Namekawa SH, VandeBerg JL, McCarrey JR, Lee JT (2007) Sex chromosome silencing in the marsupial male germ line. Proc Natl Acad Sci USA 104:9730–9735
Nanassy L, Liu L, Griffin J, Carrell DT (2011) The clinical utility of the protamine 1/protamine 2 ratio in sperm. Protein Pept Lett 18:772–777
Nazarov IB, Shlyakhtenko LS, Lyubchenko YL, Zalenskaya IA, Zalensky AO (2008) Sperm chromatin released by nucleases. Syst Biol Reprod Med 54:37–46
Olszewska M, Wiland E, Kurpisz M (2008) Positioning of chromosome 15, 18, X and Y centromeres in sperm cells of fertile individuals and infertile patients with increased level of aneuploidy. Chromosome Res 16:875–890
Pai DA, Engelke DR (2010) Spatial organization of genes as a component of regulated expression. Chromosoma (Berl) 119:13–25
Parada LA, Sotiriou S, Misteli T (2004) Spatial genome organization. Exp Cell Res 296:64–70
Pittoggi C, Renzi L, Zaccagnini G, Cimini D, Degrassi F, Giordano R, Magnano AR, Lorenzini R, Lavia P, Spadafora C (1999) A fraction of mouse sperm chromatin is organized in nucleosomal hypersensitive domains enriched in retroposon DNA. J Cell Sci 112:3537–3548
Powell D, Cran DG, Jennings C, Jones R (1990) Spatial organization of repetitive DNA sequences 500 in the bovine sperm nucleus. J Cell Sci 97:185–191
Ramalho-Santos J, Sutovsky P, Simerly C, Oko R, Wessel GM, Hewitson L, Schatten G (2000) ICSI choreography: fate of sperm structures after monospermic rhesus ICSI and first cell cycle implications. Hum Reprod 15:2610–2620
Ryu HM, Lin WW, Lamb DJ, Chuang W, Lipshultz LI, Bischoff FZ (2001) Increased chromosome X, Y, and 18 nondisjunction in sperm from infertile patients that were identified as normal by strict morphology: implication for intracytoplasmic sperm injection. Fertil Steril 76:879–883
Sbracia M, Baldi M, Cao D, Sandrelli A, Chiandetti A, Poverini R, Aragona C (2002) Preferential location of sex chromosomes, their aneuploidy in human sperm, and their role in determining sex chromosome aneuploidy in embryos after ICSI. Hum Reprod 17:320–324
Schneider R, Grosschedl R (2007) Dynamics and interplay of nuclear architecture, genome organization, and gene expression. Genes Dev 21:3027–3043
Shi Q, Martin RH (2001) Aneuploidy in human spermatozoa: FISH analysis in men with constitutional chromosomal abnormalities, and in infertile men. Reproduction 121:655–666
Simon L, Castillo J, Oliva R, Lewis SE (2011) Relationships between human sperm protamines, DNA damage and assisted reproduction outcomes. Reprod Biomed Online 23:724–734
Singleton S, Mudrak O, Morshedi M, Oehninger S, Zalenskaya I, Zalensky A (2007) Characterisation of a human sperm cell subpopulation marked by the presence of the TSH2B histone. Reprod Fertil Dev 19:392–397
Solov’eva L, Svetlova M, Bodinski D, Zalensky AO (2004) Nature of telomere dimers and chromosome looping in human spermatozoa. Chromosome Res 12:817–823
Sotolongo B, Huang TT, Isenberger E, Ward WS (2005) An endogenous nuclease in hamster, mouse, and human spermatozoa cleaves DNA into loop-sized fragments. J Androl 26:272–280
Sun HB, Yokota H (1999) Correlated positioning of homologous chromosomes in daughter fibroblast cells. Chromosome Res 7:603–610
Sutovsky P, Hewitson L, Simerly CR, Tengowski MW, Navara CS, Haavisto A, Schatten G (1996) Intracytoplasmic sperm injection for Rhesus monkey fertilization results in unusual chromatin, cytoskeletal, and membrane events, but eventually leads to pronuclear development and sperm aster assembly. Hum Reprod 11:1703–1712
Tempest HG, Griffin DK (2004) The relationship between male infertility and increased levels of sperm disomy. Cytogenet Genome Res 107:83–94
Terada Y, Luetjens CM, Sutovsky P, Schatten G (2000) Atypical decondensation of the sperm nucleus, delayed replication of the male genome, and sex chromosome positioning following intracytoplasmic human sperm injection (ICSI) into golden hamster eggs: does ICSI itself introduce chromosomal anomalies? Fertil Steril 74:454–460
Tilgen N, Guttenbach M, Schmid M (2001) Heterochromatin is not an adequate explanation for close proximity of interphase chromosomes 1–Y, 9–Y, and 16–Y in human spermatozoa. Exp Cell Res 265:283–287
Tsend-Ayush E, Dodge N, Mohr J, Casey A, Himmelbauer H, Kremitzki CL, Schatzkamer K, Graves T, Warren WC, Grützner F (2009) Higher-order genome organization in platypus and chicken sperm and repositioning of sex chromosomes during mammalian evolution. Chromosoma (Berl) 118:53–69
Tunc O, Thompson J, Tremellen K (2009) Improvement in sperm DNA quality using an oral antioxidant therapy. Reprod Biomed Online 18:761–768
Turner JM (2007) Meiotic sex chromosome inactivation. Development (Camb) 134:1823–1831
Turner JM, Mahadevaiah SK, Elliott DJ, Garchon HJ, Pehrson JR, Jaenisch R, Burgoyne PS (2002) Meiotic sex chromosome inactivation in male mice with targeted disruptions of Xist. J Cell Sci 115:4097–4105
van der Heijden GW, Ramos L, Baart EB, van den Berg IM, Derijck AA, van der Vlag J, Martini E, de Boer P (2008) Sperm-derived histones contribute to zygotic chromatin in humans. BMC Dev Biol 8:34
Ward WS (2010) Function of sperm chromatin structural elements in fertilization and development. Mol Hum Reprod 16:30–36
Ward MA, Ward WS (2004) A model for the function of sperm DNA degradation. Reprod Fertil Dev 16:547–554
Watson JM, Meyne J, Graves JA (1996) Ordered tandem arrangement of chromosomes in the sperm heads of monotreme mammals. Proc Natl Acad Sci USA 93:10200–10205
Wiland E, Zegalo M, Kurpisz M (2008) Interindividual differences and alterations in the topology of chromosomes in human sperm nuclei of fertile donors and carriers of reciprocal translocations. Chromosome Res 16:291–305
Wykes SM, Krawetz SA (2003) The structural organization of sperm chromatin. J Biol Chem 278:29471–29477
Zalenskaya IA, Zalensky AO (2004) Non-random positioning of chromosomes in human sperm nuclei. Chromosome Res 12:163–173
Zalenskaya IA, Bradbury EM, Zalensky AO (2000) Chromatin structure of telomere domain in human sperm. Biochem Biophys Res Commun 279:213–218
Zalensky A, Zalenskaya I (2007) Organization of chromosomes in spermatozoa: an additional layer of epigenetic information? Biochem Soc Trans 35:609–611
Zalensky AO, Breneman JW, Zalenskaya IA, Brinkley BR, Bradbury EM (1993) Organization of centromeres in the decondensed nuclei of mature human sperm. Chromosoma (Berl) 102:509–518
Zalensky AO, Allen MJ, Kobayashi A, Zalenskaya IA, Balhorn R, Bradbury EM (1995) Well-defined genome architecture in the human sperm nucleus. Chromosoma (Berl) 103:577–590
Zalensky AO, Tomilin NV, Zalenskaya IA, Teplitz RL, Bradbury EM (1997) Telomere–telomere interactions and candidate telomere binding protein(s) in mammalian sperm cells. Exp Cell Res 232:29–41
Zalensky AO, Siino JS, Gineitis AA, Zalenskaya IA, Tomilin NV, Yau P, Bradbury EM (2002) Human testis/sperm-specific histone H2B (hTSH2B). Molecular cloning and characterization. J Biol Chem 277:43474–43480
Acknowledgments
The authors thank Dr. Maria Svetlova for her valuable comments on the manuscript. This work was supported by RFBR grant 12-04-01489-a.
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Mudrak, O.S., Solovjeva, L.V., Chagin, V.O. (2013). Organization of Chromosomes in Human Sperm Nucleus. In: Yurov, Y., Vorsanova, S., Iourov, I. (eds) Human Interphase Chromosomes. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6558-4_8
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