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Human Reproduction Update Advance Access originally published online on February 15, 2008
Human Reproduction Update 2008 14(3):275-288; doi:10.1093/humupd/dmn002
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

The potential roles for embryotrophic ligands in preimplantation embryo development

Chris O’Neill1

Disciplines of Medicine and Physiology, University of Sydney, Human Reproduction Unit, Royal North Shore Hospital, St Leonards, NSW 2065, Australia

1 Correspondence address. E-mail: chriso{at}med.usyd.edu.au

Identification of the role(s) extracellular ligands play in regulating the development of the mammalian preimplantation embryo is a controversial area. Unequivocal evidence for their role is complicated by the apparent overlapping actions of multiple ligands. The discovery that the embryo also releases its own repertoire of ligands and expresses their corresponding receptors has further constrained analysis of their roles. Conventional ligand ablation strategies have limited utility when the cell responding to multiple ligands also produces them. The application of methods for identifying signal transduction events that occur in the early embryo in response to ligands has allowed direct assessment of the actions of these putative trophic ligands. A range of ligands induce phosphatidylinositol-3-kinase mediated survival signalling, and this is required for normal embryo development. Survival signalling maintains apoptotic pathways in a latent state within normal somatic cells, and they may fulfill the same role in the early embryo. Survival signals can also mitigate the adverse response of embryos to genotoxic and non-genotoxic stressors. Currently, there is no unequivocal evidence for a direct role of these ligands in the induction of mitosis in the early embryo. Embryotrophic ligands, acting via their specific receptors, to activate a network of effectors to create pro-survival, anti-apoptotic settings within the preimplantation embryo and these are required for normal embryo survival.

Key words: 1-o-phosphatidylinositol-3-kinase / platelet-activating factor / P53 / AKT / calcium

Received on October 22, 2007; revised November 28, 2007; accepted on January 8, 2008


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