Individual Blastomeres of 4-cell stage human embryos are able to develop into blastocysts with inner cell mass and trophectoderm

The four blastomeres of a 4-cell stage human embryo are able to develop individually into blastocysts with inner cell mass and trophectoderm

Hilde Van de Velde1,2,4, Greet Cauffman1, Herman Tournaye1,2, Paul Devroey1,2 and Inge Liebaers1,3
1 Research Centre Reproduction and Genetics, Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, 1090 Brussels, Belgium 2 Centre for Reproductive Medicine, UZ Brussel, Belgium 3 Centre for Medical Genetics, UZ Brussel, Belgium

4 Correspondence address. Tel: +32-24776696; Fax: +32-24776692; E-mail:

BACKGROUND: Early mammalian blastomeres are thought to be flexible and totipotent allowing the embryo to overcome perturbations in its organization during preimplantation development. In the past, experiments using single blastomeres from 2-, 4- and 8-cell stage mammalian embryos have provided evidence that at least some of the isolated cells can develop into healthy fertile animals and therefore are totipotent. We investigated whether isolated blastomeres of human 4-cell stage embryos could develop in vitro into blastocysts with trophectoderm (TE) and inner cell mass (ICM).

METHODS: Six 4-cell stage human embryos were split and the four blastomeres were cultured individually. The expression of NANOG, a marker for ICM cells, was analysed by immunocytochemistry.

RESULTS: The majority of the blastomere-derived embryos followed the normal pattern of development with compaction on Day 4 and cavitation on Day 5 and developed into small blastocysts with TE and ICM on Day 6 (n = 12). The four cells of one embryo were individually capable of developing into blastocysts with TE and ICM, and NANOG was expressed in the ICM.

CONCLUSIONS: Although based on a small number of embryos, we conclude that the blastomeres of a 4-cell stage human embryo are flexible and able to develop into blastocysts with ICM and TE.

Key words: blastomere/totipotent/inner cell mass/NANOG/blastocyst