Human gene expression first occurs between the four- and eight-cell stages of preimplantation development

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Abstract
The earliest stages of development in most animals, including the few mammalian species that have been investigated, are regulated by maternally inherited information1. Dependence on expression of the embryonic genome cannot be detected until the mid two-cell stage in the mouse2–4, the four-cell stage in the pig (J. Osborn & C. Polge, personal communication), and the eight-cell stage in the sheep5. Information about the timing of activation of the embryonic genome in the human is of relevance not only to the therapeutic practice of in vitro fertilization and embryo transfer (IVF), but more importantly for the successful development of techniques for the preimplantation diagnosis of certain inherited genetic diseases6–8. We describe here changes in the pattern of polypeptides synthesized during the pre-implantation stages of human development, and demonstrate that some of the major qualitative changes which occur between the four- and eight-cell stages are dependent on transcription. In addition, it appears that cleavage is not sensitive to transcriptional inhibition until after the four-cell stage.