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Expression of genes involved in early cell fate decisions in human embryos and their regulation by growth factors

¹ Faculty of Life Sciences² Faculty of Medical and Human Sciences, University of Manchester, Manchester M13 9PT, UK³ Department of Reproductive Medicine, St Mary's Hospital, Manchester M13 OJH, UK⁴ Department of Biology, University of York, York YO10 5YW, UK⁵ Division of Human Genetics, University of Southampton, Southampton SO16 6YD, UK⁶ Assisted Conception Unit, Leeds General Infirmary, Leeds LS1 3EX, UK

Correspondence should be addressed to S J Kimber who is now at University of Manchester, Core Technology Facility, 46 Grafton St, Manchester M13 9NT, UK; Email: susan.kimber{at}manchester.ac.uk

Little is understood about the regulation of gene expression in human preimplantation embryos. We set out to examine the expression in human preimplantation embryos of a number of genes known to be critical for early development of the murine embryo. The expression profile of these genes was analysed throughout preimplantation development and in response to growth factor (GF) stimulation. Developmental expression of a number of genes was similar to that seen in murine embryos (OCT3B/4, CDX2, NANOG). However, GATA6 is expressed throughout preimplantation development in the human. Embryos were cultured in IGF-I, leukaemia inhibitory factor (LIF) or heparin-binding EGF-like growth factor (HBEGF), all of which are known to stimulate the development of human embryos. Our data show that culture in HBEGF and LIF appears to facilitate human embryo expression of a number of genes: ERBB4 (LIF) and LIFR and DSC2 (HBEGF) while in the presence of HBEGF no blastocysts expressed EOMES and when cultured with LIF only two out of nine blastocysts expressed TBN. These data improve our knowledge of the similarities between human and murine embryos and the influence of GFs on human embryo gene expression. Results from this study will improve the understanding of cell fate decisions in early human embryos, which has important implications for both IVF treatment and the derivation of human embryonic stem cells.