Paint/DAPI Analysis of Mouse Zygotes to Detect Paternally Transmitted Chromosomal Aberrations

  • Francesco Marchetti
  • Andrew J. Wyrobek
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 518)

Abstract

Chromosomal abnormalities transmitted through gametes are associated with pregnancy loss, infant mortality, developmental and morphological defects, infertility and genetic diseases including cancer (Chandley, 1991; Wyrobek, 1993; Hassold et al, 1996; McFadden and Friedman, 1997; Wyrobek et al., 2000; Hassold and Hunt, 2001). These abnormalities are typically de novo events that originate in the germ cells of either parent. The relative parental contribution to transmitted chromosomal aberrations has been shown to depend on the specific chromosomes and defects that are involved. Autosomal aneuploidies are predominantly maternal in origin (Hassold et al, 1996; Hassold and Hunt, 2001), while sex chromosomal aneuploidies have a substantial paternal contribution (Hassold et al, 1993; Hassold, 1998). In addition, more than 80% of de novo structural chromosomal abnormalities among livebirths appear to be paternally derived (Olson and Magenis, 1988; Overhauser et al., 1990; Chandley, 1991; Dallapiccola et al., 1993; Cody et al., 1997). There is epidemiological evidence linking paternal occupational or environmental exposure to abnormal reproductive outcomes (Narod et al., 1988; Savitz and Chen, 1990; Olshan, 1995]); however, despite the health risk to the developing embryo and offspring, little is known about the etiology of paternally-derived chromosomal abnormalities. Research with laboratory animals is essential for identifying and characterizing reproductive toxicants and for assessing the human risk of exposure to such agents

Keywords

Melphalan Cyclophosphamide Hunt DAPI Biotin 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

REFERENCES

  1. Adachi, Y., Luke, M. and Lacmmli, U.K., 1991, Chromosome assembly in vitro: topoisomerase II is required for condensation. Cell. 643:137–148.CrossRefGoogle Scholar
  2. Adler, I.D., 1990, Clastogenic effects of acrylamide in different germ-cell stages of male mice, in: Banbury Report 34: Biology of Mammalian Germ Cell Mutagenesis, Cold Spring Harbor, Cold Spring Harbor Laboratory Press, pp. 115–131.Google Scholar
  3. Adler, I.D., Reitmeir, P., Schmoller, R. and Schriever-Schwemmer, G., 1994, Dose response for heritable translocations induced by acrylamide in spermatids of mice. Mutat Res. 309:285–291.PubMedCrossRefGoogle Scholar
  4. Adler, I.D., Schriever-Schwemmer, G. and Kliesch, U., 1994, Clastogenicity of trophosphamide in somatic and germinal cells of mice. Mutat Res. 307:237–243.PubMedCrossRefGoogle Scholar
  5. Albanese, R., 1982, The use of fertilized mouse eggs in detecting potential clastogens. Mutat Res. 97:315–326.PubMedCrossRefGoogle Scholar
  6. Anderson, R.D. and Berger, N.A., 1994, Mutagenicity and carcinogenicity of topoisomerase-interactive agents. Mutat Res. 309:109–142.PubMedCrossRefGoogle Scholar
  7. Arrighi, F.E. and Hsu, T.C., 1971, Localization of hcterochromatin in human chromosomes. Cytogenetics. 10:81–86.PubMedCrossRefGoogle Scholar
  8. Boci, J.J.W.A., Balajee, A.S., de Boer, P., Rens, W., Aten, J.A., Mullenders, L.H. and Natarajan, A.T., 1994, Construction of mouse chromosome-specific DNA libraries and their use for the detection of X-rayinduced aberrations. M J Rad Biol. 65:583–590.Google Scholar
  9. Breneman, J.W., Ramsey, M.J., Lee, D.A., Eveleth, G.G., Minkler, J.L. and Tucker, J.D., 1993, The development of chromosome-specific composite probes for the mouse and their application to chromosome painting. Chromosoma. 102:591–598.PubMedCrossRefGoogle Scholar
  10. Breneman, J.W., Swiger, R.R., Ramsey, M.J., Minkler, J.L., Eveleth, G.G., Langlois, R.A. and Tucker, J.D., 1995, The development of painting probes for dual-color and multiple chromosome analysis in the mouse, Cytogenet. Cell Genet. 68:197–202.PubMedCrossRefGoogle Scholar
  11. Cattanach, B.M., Pollard, C.E. and Isaacson, J.H., 1968, Ethyl methanesulphonate-induced chromosome breakage in the mouse. Mutat Res. 6:297–307.PubMedCrossRefGoogle Scholar
  12. Chandley, A.C., 1991. On the paternal origin of de novo mutation in men. J Med Genet. 28:217–223.Google Scholar
  13. Clarke, H.J. and Masui, Y., 1986, Transformation of sperm nuclei to metaphase chromosomes in the cytoplasm of maturing oocytes of the mouse. J Cell Biol. 102:1039–1046.PubMedCrossRefGoogle Scholar
  14. Cody, J.D., Pierce, J.F., Brkanac, Z., Plaetke, R., Ghidoni, P.D., Kaye, C. and Leach, R.J., 1997, Preferential loss of the paternal alleles in the 18q-syndrome. Am J Med Genet. 69:280–286.PubMedCrossRefGoogle Scholar
  15. Dallapiccola, B., Mandich, P., Bellone, E., Selicorni, A., Mokin, V., Ajmar, F. and Novelli, G., 1993, Parental origin of chromosome 4p deletion in Wolf-Hirschhorn syndrome. Am J Med Genet. 47:921–924.PubMedCrossRefGoogle Scholar
  16. De Mas, P., Daudin, M., Vincent, M.C., Bourrouillou, G., Calvas, P., Mieusset, R. and Bujan, L., 2001, Increased aneuploidy in spermatozoa from testicular tumor patients after chemotherapy with cisplatin, etoposide and bleomycin. Hum Reprod. 16:1204–1208.PubMedCrossRefGoogle Scholar
  17. Dearfield, K.L., Douglas, G.R., Ehling, U.H., Moore, M.M., Sega, G.A. and Brusick, DJ., 1995, Acrylamide: a review of its genotoxicity and an assessment of heritable genetic risk. Mutat Res. 330:71–99.PubMedCrossRefGoogle Scholar
  18. DiNardo, S., Voelkel, K. and Sternglanz, R., 1984, DNA topoisomerase II mutant of Saccharomices cerevisiae: topoisomerase II is required for segregation of daughter molecules at the termination of DNA replication. Proc Natl Acad Sci USA. 81:2616–2620.PubMedCrossRefGoogle Scholar
  19. Donahue, R.P.. 1972, Cytogenetic analysis of the first cleavage division in mouse embryos. Proc Natl Acad Sci USA. 69:74–77.PubMedCrossRefGoogle Scholar
  20. Downes, C.S., Mullinger, A.M. and Johnson, R., 1991, Inhibitors of DNA topoisomerase II prevent chromatid separation in mammalian cells but do not prevent from exit from meiosis. Proc Natl Acad Sci USA. 88:8895–8899.PubMedCrossRefGoogle Scholar
  21. Ehling, U.H., Cumming, R.B. and Mailing, H.V., 1968, Induction of dominant lethal mutations by alkylating agents in male mice. Mutat Res. 5:417–428.PubMedCrossRefGoogle Scholar
  22. Ehling, U.H. and Neuhäuser-Klaus, A., 1988, Induction of specific-locus and dominant-lethal mutations by cyclophosphamide and combined cyclophosphamide-radiation treatment in male mice. Mutat Res. 199:21–30.PubMedGoogle Scholar
  23. Ehling, U.H. and Neuhäuser-Klaus, A., 1994, Induction of specific-locus and dominant lethal mutations in male mice by trophosphamide. Mutat Res. 307:229–236.PubMedCrossRefGoogle Scholar
  24. Ehling, U.H. and Neuhäuser-Klaus, A., 1995, Induction of specific-locus and dominant lethal mutations in male mice by n-propyl and isopropyl methanesulphonate. Mutat Res. 328:73–82.PubMedCrossRefGoogle Scholar
  25. Ferguson, L.R. and Baguley, B.C., 1994, Topoisomerase II enzymes and mutagenicity. Environ Mol Mutagen. 24:245–261.PubMedCrossRefGoogle Scholar
  26. Ferguson, L.R. and Baguley, B.C., 1996, Mutagenicity of anticancer drugs that inhibit topoisomerase enzymes. Mutat Res. 355:91–101.PubMedCrossRefGoogle Scholar
  27. Garagna, S. and Redi, C., 1988, Chromatin topology during the transformation of the mouse sperm nucleus into pronucleus in vivo. J Exp Zool. 246:187–193.PubMedCrossRefGoogle Scholar
  28. Gassner, P. and Adler, I.D., 1996, Induction of hypoploidy and cell cycle delay by acrylamide in somatic and germinal cells of male mice. Mutat Res. 367:195–202.PubMedCrossRefGoogle Scholar
  29. Generoso, W.M., Cain, K.T., Cornett, C.C. and Cacheiro, N.L.A., 1984, DNA target sites associated with chemical induction of dominant-lethal mutations and heritable translocations in mice, in: Genetics: New Frontiers, V.L. Chopra, B.C. Joshi, R.P. Sharma and U.C. Bansal, eds., New Delhi, Oxford and IBH, 1: 347–356.Google Scholar
  30. Generoso, W.M., Cain, K.T., Cornett, C.V., Cacheiro, N.L.A. and Hughes, L.A., 1990, Concentrationresponse curves for ethylene-oxide-induced heritable translocations and dominant lethal mutations. Environ Mol Mutagen. 16:126–131.PubMedCrossRefGoogle Scholar
  31. Generoso, W.M., Cain, K.T., Hughes, L.A., Sega, G.A., Braden, P.W., Gosslee, D.G, and Shelby, M.D., 1986, Ethylene oxide dose and dose-rate effects in the mouse dominant-lethal test. Environ Mutagen. 8:1–7.PubMedCrossRefGoogle Scholar
  32. Generoso, W.M., Cain, K.T., Krishna, M. and Huff, S.W., 1979, Genetic lesions induced by chemicals in spermatozoa and spermatids of mice are repaired in the egg. Proc Natl Acad Sci USA. 76:435–437.PubMedCrossRefGoogle Scholar
  33. Generoso, W.M., Witt, K.L., Cain, K.T., Hughes, L., Cacheiro, NX., Lockhart, A.M. and Shelby, M.D., 1995, Dominant lethal and heritable translocation tests with chlorambucil and melphalan in male mice. Mutat Res. 345:167–180.PubMedCrossRefGoogle Scholar
  34. Hassold, T., Abruzzo, M., Adkins, K., Griffin, D., Merrill, M., Millie, E., Saker, D., Shen, J. and Zaragoza, M., 1996, Human aneuploidy: incidence, origin, and etiology. Environ Mol Mutagen. 28:167–175.PubMedCrossRefGoogle Scholar
  35. Hassold, T. and Hunt, P., 2001, To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet. 2:280–291.PubMedCrossRefGoogle Scholar
  36. Hassold, T., Hunt, P.A. and Sherman, S., 1993, Trisomy in humans: incidence, origin and etiology. Curr Opin Genet Develop. 3:398–403.CrossRefGoogle Scholar
  37. Hassold, T.J., 1998, Nondisjunction in the human male. Curr Top Develop Biol. 37:383–406.CrossRefGoogle Scholar
  38. Kirk, K. M. and Lyon, M. F., 1984, Induction of congenital malformations in the offspring of male mice treated with X-rays at pre-meiotic and post-meiotic stages. Mutat Res. 125: 75–85.PubMedCrossRefGoogle Scholar
  39. Lang, R. and Adler, I.D., 1977, Heritable translocation test and dominant lethal-assay in male mice treated with methyl methanesulphonate. Mutat Res. 48:75–88.PubMedCrossRefGoogle Scholar
  40. Liu, L.F., 1989, DNA topoisomerase poisons as antitumor drugs. Annu Rev Biochem. 58:351–375.PubMedCrossRefGoogle Scholar
  41. Mailhes, J.B. and Marchetti, F., 1994, Chemically-induced aneuploidy in mammalian oocytes. Mutat Res. 320:87–111.PubMedCrossRefGoogle Scholar
  42. Mailhes, J.B. and Yuan, Z.P., 1987, Cytogenetic technique for mouse metaphase II oocytes. Gamete Res. 18:77–83.PubMedCrossRefGoogle Scholar
  43. Marchetti, F., Bishop, J.B., Lowe, X., Generoso, W.M., Hozier, J. and Wyrobek, A.J., 2001b, Etoposide induces heritable chromosomal aberrations and aneuploidy during male meiosis in the mouse. Proc Natl Acad Sci USA. 98:3952–3957.PubMedCrossRefGoogle Scholar
  44. Marchetti, F., Lowe, X., Bishop, J. and Wyrobek, A.J., 1997, Induction of chromosomal aberrations in mouse zygotes by acrylamide treatment of male germ cells and their correlation with dominant lethality and heritable translocations. Environ Mol Mutagen. 30:410–417.PubMedCrossRefGoogle Scholar
  45. Marchetti, F., Lowe, X., Moore, D. II, Bishop, J. and Wyrobek, A.J., 1996, Paternally inherited chromosomal structural aberrations detected in mouse first-cleavage zygote metaphases by multicolor fluorescence in situ hybridization painting. Chromosome Res. 4:604–613.PubMedCrossRefGoogle Scholar
  46. Marchetti, F. and Mailhes, J.B., 1994, Variation of mouse oocyte sensitivity to griseofulvin-induced aneuploidy and meiotic delay during the first meiotic division. Environ Mol Mutagen. 23:179–185.PubMedCrossRefGoogle Scholar
  47. Marchetti, F., Sloter, E. and Wyrobek, A. J., 2001a, Advances in understanding paternally transmitted chromosomal abnormalities, in: Teplice program: Impact of air pollution on human health. R. J. Sram, ed., Prague, Academia, pp. 193–205.Google Scholar
  48. Marchetti, F., Tiveron, C., Bassani, B. and Pacchierotti, F., 1992, Griseofulvin-induced aneuploidy and meiotic delay in female mouse germ cells. II. Cytogenetic analysis of one-cell zygotes. Mutat Res. 266:151–162.PubMedCrossRefGoogle Scholar
  49. Matsuda, Y., Seki, N., Utsugi-Takeuchi, T. and Tobari, I., 1989, Change in X-ray sensitivity of mouse eggs from fertilization to the early pronuclear stage, and their repair capacity. Int J Rad Biol. 55:233–256.PubMedCrossRefGoogle Scholar
  50. Matsuda, Y., Seki, N., Utsugi-Takeuchi, T. and Tobari, I., 1989, X-Ray-and mitomycin C (MMC)-induced chromosome aberrations in spermiogenic germ cells and the repair capacity of mouse eggs for the Xray and MMC damage. Mutat Res. 211:65–75.PubMedCrossRefGoogle Scholar
  51. Matsuda, Y. and Tobari, I., 1988, Chromosomal analysis in mouse eggs fertilized in vitro with sperm exposed to ultraviolet light (UV) and methyl and ethyl methanesulphonate (MMS and EMS). Mutat Res. 198:131–144.PubMedCrossRefGoogle Scholar
  52. McFadden, D. and Friedman, J., 1997, Chromosome abnormalities in human beings. Mutat Res. 396:129–140.PubMedCrossRefGoogle Scholar
  53. McGaughey, R.W. and Chang, M.C., 1969, Meiosis of mouse egg before and after sperm penetration. J Exp Zool. 170:397–410.PubMedCrossRefGoogle Scholar
  54. Meistrich, M.L., Brock, W.A., Grimes, S.R., Platz, R.D. and Hnilica, L.S., 1978, Nucleoprotein transitions during spermatogenesis. FASEB J. 37:2522–2525.Google Scholar
  55. Mitelman, F., Kaneko, Y. and Trent, J., 1991, Report of the committee on chromsome changes in neoplasia. Cytogenet Cell Genet. 58:1053–1079.CrossRefGoogle Scholar
  56. Narod, S.A., Douglas, G.R., Nestmann, E.R. and Blackey, D.H., 1988, Human mutagens: evidence from paternal exposure. Environ Mol Mutagen. 11:401–415.PubMedCrossRefGoogle Scholar
  57. Newport, J. and Dunphy, W., 1992, Characterization of the membrane binding and fusion events during nuclear envelope assembly using purified components. J Cell Biol. 116:295–306.PubMedCrossRefGoogle Scholar
  58. Nomura, T., 1982, Parental exposure to x rays and chemicals induces heritable tumours and anomalies in mice. Nature. 296:575–577.PubMedCrossRefGoogle Scholar
  59. Nomura, T., 1988, X-Ray-and chemically induced germ-line mutation causing phenotypical anomalies in mice. Mutat Res. 188:309–320.Google Scholar
  60. Nonchev, S. and Tsanev, R., 1990, Protamine-histone replacement and DNA replication in the male mouse pronucleus. Mol Reprod Dev. 25:72–76.PubMedCrossRefGoogle Scholar
  61. Olshan, A. F., 1995, Lessons learned from epidemiologic studies of environmental exposure and genetic disease. Environ Mol Mutagen. 25, Suppl 26:74–80.PubMedCrossRefGoogle Scholar
  62. Olson, S.B. and Magenis, R.E., 1988, Preferential paternal origin of de novo structural chromosome rearrangements, in: The Cytogenetics of Mammalian Autosomal Rearrangements, A. Daniel, ed., New York, Liss, pp. 583–599.Google Scholar
  63. Overhauser, J., McMahon, J., Oberlender, S., Carlin, M.E., Niebuhr, E., Wasmuth, J.J. and Lee-Chen, J., 1990, Parental origin of chromosome 5 deletions in the cri-du-chat syndrome. Am J Med Genet. 37:83–86.PubMedCrossRefGoogle Scholar
  64. Pacchierotti, F., Tiveron, C., D’Archivio, M., Bassani, B., Cordelli, E., Leter, G. and Spanò, M., 1994, Acrylamide-induced chromosomal damage in male mouse germ cells detected by cytogenetic analysis of one-cell zygotes. Mutat Res. 309:273–284.PubMedCrossRefGoogle Scholar
  65. Perreault, S.D., 1990, Regulation of sperm nuclear rectivation during fertilization, in: Fertilization in Mammals, B.D. Bavister, J. Cumming and E.R.S. Roldan, eds., Norwell, MA, Serono Symphosia, pp. 285–296.Google Scholar
  66. Perreault, S.D., 1992, Chromatin remodeling in mammalian zygotes. Mutat Res. 296:43–55.PubMedCrossRefGoogle Scholar
  67. Preston, R.J., 1994, Future of germ cell cytogenetics. Environ Mol Mutagen. 23:54–58.PubMedCrossRefGoogle Scholar
  68. Rose, D., Thomas, W. and Holm, C., 1990, Segregation of recombined chromosomes in meiosis I requires DNA topoisomerase II. Cell. 60:1009–1017.PubMedCrossRefGoogle Scholar
  69. Russell, L., 1994, Effects of spermatogenic cell type on quantity and quality of mutations, in: Male-Mediated Developmental Toxiciiy, A. Olsham and D. Mattison, eds., New York, Plenum Press, pp. 37–48.CrossRefGoogle Scholar
  70. Savitz, D.A. and Chen, J., 1990, Paternal occupation and childhood cancer: review of epidemiologic studies. Environm Health Perspect. 88:325–358.CrossRefGoogle Scholar
  71. Sega, G.A., 1979, Unscheduled DNA synthesis (DNA repair) in the germ cells of male mice: its role in the study of mammalian mutagenesis. Genetics. 92:349–358.Google Scholar
  72. Sega, G.A., Valdivia Alcota, R.P., Tancongco, C.P. and Brimer, P., 1989, Acrylamide binding to the DNA and protamine of spermiogenic stages of the mouse and its relationship to genetic damage. Mutat Res. 216:221–230.PubMedCrossRefGoogle Scholar
  73. Shelby, M.D., 1996, Selecting chemicals and assays for assessing mammalian germ cell mutagenicity. Mutat Res. 325:159–167.Google Scholar
  74. Shelby, M.D., Bishop, J.B., Hughes, L., Morris, R.W. and Generoso, W.M., 2001, Dominant lethal and heritable translocation effects of etoposide in male mice, in press.Google Scholar
  75. Shelby, M.D., Bishop, J.B., Mason, J. M. and Tindall, K.R., 1993, Fertility, reproduction, and genetic disease: studies on the mutagenic effects of environmental agents on mammalian germ cells. Environm Health Perspect. 100:283–291.CrossRefGoogle Scholar
  76. Shelby, M.D., Cain, K.T., Cornett, C.V. and Generoso, W.M.. 1987, Acrylamide: induction of heritable translocations in male mice. Environ Mol Mutagen. 9:363–368.Google Scholar
  77. Shelby, M.D., Cain, K.T., Hughes, L.A., Braden, P.W. and Generoso, W.M., 1986, Dominant lethal effects of acrylamide in male mice. Mutat Res. 173:35–40.PubMedCrossRefGoogle Scholar
  78. Simerly, C.R., Hecht, N.B., Goldberg, E. and Schatten, G., 1993, Tracing the incorporation of the sperm tail in the mouse zygote and early embryo using an anti-testicular alpha-tubulin antibody. Dev Biol. 158:536–548.PubMedCrossRefGoogle Scholar
  79. Smith, P.J., 1990, DNA topoisomerase dysfunction: a new goal for antitumor chemotherapy. BioEssays. 12:167–172.PubMedCrossRefGoogle Scholar
  80. Sotomayor, R.E. and Cumming, R.B., 1975, Induction of translocations by cyclophosphamide in different germ cell stages of male mice: cytological characterization and transmission. Mutat Res. 27:375–388.PubMedCrossRefGoogle Scholar
  81. Tanaka, N., Katoh, M. and Iwahar, S., 1981, Formation of chromosome-type aberrations at the first cleavage after MMS treatment in late spermatids of mice. Cytogenet Cell Genet. 31:145–152.PubMedCrossRefGoogle Scholar
  82. Tucker, J.D., Morgan, W.F., Aw, A.A., Bauchinger, M., Blakey, D., Cornforth, M.N., Littlefield, L.G., Natarajan, A.T. and Shasserre, C. 1995, A proposed system for scoring structural aberrations detected by chromosome painting, Cytogenet. Cell Genet. 68:211–221.PubMedCrossRefGoogle Scholar
  83. Wang, J.C., Caron, P.R. and Kim, R.A., 1990, The role of DNA topoisomerases in recombination and genome stability: a double-edged sword? Cell. 62:403–406.PubMedCrossRefGoogle Scholar
  84. Wyrobek, A.J., 1993, Methods and concepts in detecting abnormal reproductive outcomes of paternal origin. Reprod Toxicol. 7:3–16.PubMedCrossRefGoogle Scholar
  85. Wyrobek, A.J., Marchetti, F., Sloter, E. and Bishop, J., 2000, Chromosomally defective sperm and their developmental consequences, in: Human Monitoring after Environmental and Occupational Exposure to Chemical and Physical Agents, D. Anderson, A.E. Karakaya and RJ. Sram, eds., Amsterdam, IOS press. 313:134–150.Google Scholar

Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Francesco Marchetti
    • 1
  • Andrew J. Wyrobek
    • 1
  1. 1.Biology and Biotechnology Research ProgramLawrence Livermore National LaboratoryLivermoreUSA

Personalised recommendations