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Metabolic heterogeneity during preimplantation development: The missing link?

Brison, Daniel R.; Sturmey, Roger G.; Leese, Henry J.


Daniel R. Brison

Henry J. Leese


BACKGROUND Most tissues in the body rely on the presence of gap junctions in order to couple their component cells electrically and metabolically via intercellular transport of ions, metabolites and signalling agents. As a result, cells within tissues achieve a high degree of, ‘metabolic homogeneity’ which enables them to develop in an integrated way and co-ordinate their response to physiological signals and environmental cues. Unusually, the developing mammalian preimplantation embryo does not form functional gap junctions until it has divided into 8 or more cells. We discuss the implications of this ‘missing link’ during the first few days of development for the maintenance of homogeneity between embryonic cells and for the co-ordination of the embryonic response to intrinsic genetic damage and external environmental signals. METHODS No systematic review has been carried out. The physiology of preimplantation development and the general nature of gap junctions have been reviewed briefly before examining experimental evidence which addresses the following points: (i) whether there are functional differences between early blastomeres; (ii) when during preimplantation development the embryo is most sensitive to environmental perturbation and (iii) the consequences for early embryos of ablating gap junction formation and function. RESULTS AND CONCLUSIONS General conclusions are confounded by species differences, especially in the timing of embryonic genome activation (EGA) and the extent of intrinsic genotypic and phenotypic variation (low in embryos from inbred mice; high in human embryos). Nevertheless, we propose that the absence of gap junctions requires cleavage stage mammalian embryos to behave cell autonomously in a metabolic sense, contributes to their heightened sensitivity to environmental perturbation compared with the later stages of preimplantation development and poses more problems in the early human embryo, where there is a high degree of heterogeneity between the blastomeres. We argue that the legacy of metabolic heterogeneity, in part generated by the absence of gap junctions, is ‘rescued’ by the onset of apoptosis following EGA. In the context of human-assisted conception, since early embryos lacking gap junctions are more sensitive to environmental stress during cleavage, this would support transfer to the natural environment as early as possible after fertilization.


Leese, H. J., Sturmey, R. G., & Brison, D. R. (2014). Metabolic heterogeneity during preimplantation development: The missing link?. Human Reproduction Update, 20(5), 632-640.

Journal Article Type Review
Acceptance Date Mar 4, 2014
Online Publication Date May 2, 2014
Publication Date Sep 1, 2014
Deposit Date Aug 18, 2016
Journal Human reproduction update
Print ISSN 1355-4786
Electronic ISSN 1460-2369
Publisher Oxford University Press (OUP)
Peer Reviewed Peer Reviewed
Volume 20
Issue 5
Pages 632-640
Keywords Metabolism, Preimplantation embryo, Gap junctions
Public URL
Publisher URL
Additional Information This is a description of an article published in: Human reproduction update, 2014, v.20 issue 5.