Human Reproduction, Vol. 18, No. 12, 2565-2574,
December 2003
© 2003 European Society of Human Reproduction and Embryology
Chromosomally abnormal cells are not selected for the extra-embryonic compartment of the human preimplantation embryo at the blastocyst stage
1 Research Institute Growth and Development (GROW), Maastricht University, 2 Department of Obstetrics and Gynaecology, University Hospital Maastricht and 3 Department of Molecular Cell Biology and Genetics, Maastricht University, Maastricht, The Netherlands
4 To whom correspondence should be addressed at: IVF Laboratory, Department of Obstetrics and Gynaecology, Academic Hospital Maastricht, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands. e-mail: jderh{at}ms-azm-3.azm.nl
BACKGROUND: Although well defined for embryos at cleavage stages, the occurrence and frequency of chromosomal aberrations in human blastocysts is relatively unknown. It has been reported that only one in four blastocysts is comprised totally of chromosomally normal cells. One of the selection mechanisms for the embryo proper to become free of these chromosomally abnormal cells would be to sequester them to the extra-embryonic compartment during development. The study aim was to investigate whether such a mechanism of selection exists in human preimplantation embryos. METHODS: Inner cell mass (ICM)/trophectoderm (TE) differentiation was performed, followed by fluorescence in-situ hybridization (FISH), to study the chromosomal distribution in both populations of cells. RESULTS: Of the 94 successfully analysed blastocysts, 68.8 ± 1.5% of all analysable nuclei per blastocyst showed a disomic chromosomal content. Only 22.6% of blastocysts analysed were classified as normal. Of the embryos classified as abnormal at the blastocyst stage, 11.9% showed a simple mosaic pattern and 32.1% a complex mosaic pattern. An equally large group of blastocysts showed either a chaotic pattern (16.7%), or the chromosomal pattern could not be classified. The average degree of normal cells in the ICM (67.9%) was similar to the degree observed in the TE (69.5%). CONCLUSIONS: These findings indicate that chromosomally abnormal cells are not preferentially segregating to the extra-embryonic compartment of the human preimplantation embryo at the blastocyst stage. Hence, other mechanisms should be responsible for an absence of chromosomally abnormal cells in the embryo proper at later stages of development. One possible mechanism might be the elimination of the chromosomally abnormal cells by selective cell death activation.
Key words: chromosomal mosaicism/fluorescence in-situ hybridization/human blastocyst/inner cell mass/trophectoderm
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