Hostname: page-component-848d4c4894-x5gtn Total loading time: 0 Render date: 2024-05-12T11:28:46.462Z Has data issue: false hasContentIssue false

Lack of cell cycle checkpoints in human cleavage stage embryos revealed by a clonal pattern of chromosomal mosaicism analysed by sequential multicolour FISH

Published online by Cambridge University Press:  13 November 2000

R.H. Harrison
Affiliation:
Cytogenetics Department, Division of Medical & Molecular Genetics, Guy's Hospital, London SE1 9RT, UK.
H.-C. Kuo
Affiliation:
Department of Obstetrics & Gynaecology, Division of Women's & Children's Health, Guy's, King's & St Thomas' School of Medicine, King's College, London, London SE1 7EH, UK.
P.N. Scriven
Affiliation:
Cytogenetics Department, Division of Medical & Molecular Genetics, Guy's Hospital, London SE1 9RT, UK.
A.H. Handyside
Affiliation:
Department of Obstetrics & Gynaecology, Division of Women's & Children's Health, Guy's, King's & St Thomas' School of Medicine, King's College, London, London SE1 7EH, UK. School of Biology, University of Leeds, Leeds LS2 9JT, UK.
C. Mackie Ogilvie
Affiliation:
Cytogenetics Department, Division of Medical & Molecular Genetics, Guy's Hospital, London SE1 9RT, UK.

Abstract

Multicolour fluorescence in situ hybridisation (FISH) analysis of interphase nuclei in cleavage stage human embryos has highlighted a high incidence of postzygotic chromosomal mosaicism, including both aneuploid and ploidy mosaicism. Indeed, some embryos appear to have a chaotic chromosomal complement in a majority of nuclei, suggesting that cell cycle checkpoints may not operate in early cleavage. Most of these studies, however, have only analysed a limited number of chromosomes (3–5), making it difficult to distinguish FISH artefacts from true aneuploidy. We now report analysis of 11 chromosomes in five sequential hybridisations with standard combinations of two or three probes and minimal loss of hybridisation efficiency. Analysis of a series of arrested human embryos revealed a generally consistent pattern of hybridisation on which was superimposed frequent deletion of one or both chromosomes of a specific pair in two or more nuclei indicating a clonal origin and continued cleavage following chromosome loss. With a binucleate cell in a predominantly triploid XXX embryo, the two nuclei remained attached during preparation and the chaotic diploid/triphoid status of every chromosome analysed was the same for each nucleus. Furthermore, in each hybridisation the signals were distributed as a mirror-image about the plane of attachment, indicating premature decondensation during anaphase consistent with a lack of checkpoint control.

Type
Research Article
Copyright
2000 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)