ToxSci Advance Access originally published online on October 16, 2008
Toxicological Sciences 2009 107(1):194-205; doi:10.1093/toxsci/kfn209
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Published by Oxford University Press 2008.
Chromosomal Mosaicism in Mouse Two-Cell Embryos after Paternal Exposure to Acrylamide
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* Biosciences Directorate, Lawrence Livermore National Laboratory, Livermore, California 94550
Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709
Department of Psychiatry, Kaiser Permanente Medical Group, Inc, Hayward, California 94545
1 To whom correspondence should be addressed at Life Sciences Division, MS74R0157, Lawrence Berkeley National Laboratory, 1 Cyclotron Rd, Berkeley, CA 94720. Fax: (510) 486-6691. E-mail: fmarchetti{at}lbl.gov.
Received July 18, 2008; accepted September 28, 2008
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Abstract |
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Chromosomal mosaicism in human preimplantation embryos is a common cause of spontaneous abortions, however, our knowledge of its etiology is limited. We used multicolor fluorescence in situ hybridization painting to investigate whether paternally transmitted chromosomal aberrations result in mosaicism in mouse two-cell embryos. Paternal exposure to acrylamide, an important industrial chemical also found in tobacco smoke and generated during the cooking process of starchy foods, produced significant increases in chromosomally defective two-cell embryos, however, the effects were transient primarily affecting the postmeiotic stages of spermatogenesis. Comparisons with our previous study of zygotes demonstrated similar frequencies of chromosomally abnormal zygotes and two-cell embryos suggesting that there was no apparent selection against numerical or structural chromosomal aberrations. However, the majority of affected two-cell embryos were mosaics showing different chromosomal abnormalities in the two blastomeric metaphases. Analyses of chromosomal aberrations in zygotes and two-cell embryos showed a tendency for loss of acentric fragments during the first mitotic division of embryogenesis, whereas both dicentrics and translocations apparently underwent proper segregation. These results suggest that embryonic development can proceed up to the end of the second cell cycle of development in the presence of abnormal paternal chromosomes and that even dicentrics can persist through cell division. The high incidence of chromosomally mosaic two-cell embryos suggests that the first mitotic division of embryogenesis is prone to missegregation errors and that paternally transmitted chromosomal abnormalities increase the risk of missegregation leading to embryonic mosaicism.
Key Words: acrylamide; in vivo; fluorescence in situ hybridization; spermatogenesis.