Survival signalling in the preimplantation embryo

Abstract

The development of the preimplantation embryo (from fertilisation until the formation of the differentiated blastocyst) occurs without a requirement for exogenous mitogenic or survival signals. This distinguishes the behaviour of cells in the early embryo from all other normal cells. The discovery that fertilisation triggers the production and release of potent bioactive mediators by the embryo that act back on membrane receptors demonstrated the presence of closed autocrine embryotrophic loops. It is now clear that these ligands act in concert with paracrine mediators normally present within the reproductive tract to support the normal development of the embryo. These ligands act via receptors expressed by the embryo to activate signalling transduced by 1-o-phosphatidylinositol-3-kinase and the resultant formation of phosphatidylinositol-3,4,5-trisphosphate. This polyphosphorylated membrane phospholipid acts as a docking site for proteins possessing the PH domain. These include PDK1, AKT and phospholipase C. The activation of these proteins accounts for the initiation of new transcription from the embryonic genome to form a pro-survival, anti-apoptotic transcriptome and the post-transcriptional activation of pro-survival signalling within embryonic cells. This includes the attenuation of action of pro-apoptotic signals, such as P53. The production of embryotrophic ligands after fertilisation bootstraps development by the activation of transcription from the embryonic genome, followed by the activation of pro-survival settings within embryo cells.