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Regular Article |
a Laboratory of Developmental Genetics and Imprinting and
b Laboratory of Computational Neuroscience, The Babraham Institute, Babraham, Cambridge CB2 4AT, United Kingdom
ABSTRACT
Culture of preimplantation mammalian embryos and cells can influence their subsequent growth and differentiation. Previously, we reported that culture of mouse embryonic stem cells is associated with deregulation of genomic imprinting and affects the potential for these cells to develop into normal fetuses. The purpose of our current study was to determine whether culture of preimplantation mouse embryos in a chemically defined medium (M16) with or without fetal calf serum (FCS) can affect their subsequent development and imprinted gene expression. Only one third of the blastocysts that had been cultured from two-cell embryos in M16 medium complemented with FCS developed into viable Day 14 fetuses after transfer into recipients. These M16 + FCS fetuses were reduced in weight as compared with controls and M16 fetuses and had decreased expression of the imprinted H19 and insulin-like growth factor 2 genes associated with a gain of DNA methylation at an imprinting control region upstream of H19. They also displayed increased expression of the imprinted gene Grb10. The growth factor receptor binding gene Grb7, in contrast, was strongly reduced in its expression in most of the M16 + FCS fetuses. No alterations were detected for the imprinted gene Mest. Preimplantation culture in the presence of serum can influence the regulation of multiple growth-related imprinted genes, thus leading to aberrant fetal growth and development.
First decision: 25 August 2000.
1 This work was supported by the Ministry of Agriculture, Fisheries and Food, the Biotechnology and Biological Sciences Research Council, and the Royal Society.
2 Correspondence and current address: Robert Feil, Institute of Molecular Genetics, CNRS, 1919 Route du Mende, 34293 Montpellier cedex 5, France. FAX: 33 4 67040231; feil{at}jones.igm.cnrs-mop.fr
3 Current address: Wellcome/CRC Institute of Cancer and Developmental Biology, Tennis Court Road, Cambridge CB2 1QR, UK.
4 Current address: Office for National Statistics, Ebury Gate, London SW1, UK.
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