O'Neill Chris
Disciplines of Medicine and Physiology, Human Reproduction Unit, Royal North Shore Hospital, University of Sydney, St Leonards, New South Wales 2065, Australia.
Reproduction. 2008 Aug;136(2):147-56. doi: 10.1530/REP-08-0105. Epub 2008 May 30.
The development of the preimplantation mammalian embryo is an autopoietic process; once initiated development proceeds without an absolute requirement for external information or growth cues. This developmental autonomy is partly explained by the generation of autocrine trophic ligands that are released and act back on the embryo via specific receptors. Several embryotrophic ligands cause receptor-dependent activation of 1-o-phosphatidylinositol 3-kinase. This enzyme phosphorylates phosphatidylinositol-4,5-bisphosphate to form phosphatidylinositol-3,4,5-trisphosphate. Genetic or pharmacological ablation of this enzyme activity disrupts normal development of preimplantation embryos. Phosphatidylinositol-3,4,5-trisphosphate is a membrane lipid that acts as a docking site for a wide range of proteins possessing the pleckstrin homology (PH) domain. Such proteins are important regulators of cell survival, proliferation, and differentiation. RAC-alpha serine/threonine protein kinase is an important PH domain protein and its activity is required for normal preimplantation embryo development and survival. The activity of a range of PH domain proteins is also implicated in the normal development of the embryo. This review critically examines the evidence for the activation of 1-o-phosphatidylinositol 3-kinase in the generation of pleiotypic trophic response to embryotrophins in the autopoietic development of the preimplantation embryo.
植入前哺乳动物胚胎的发育是一个自我生成过程；一旦启动，发育过程无需绝对依赖外部信息或生长信号。这种发育自主性部分可由自分泌营养配体的产生来解释，这些配体被释放后通过特定受体作用于胚胎自身。几种胚胎营养配体可引起1- O -磷脂酰肌醇3-激酶的受体依赖性激活。该酶将磷脂酰肌醇-4,5-二磷酸磷酸化形成磷脂酰肌醇-3,4,5-三磷酸。这种酶活性的基因或药理学缺失会破坏植入前胚胎的正常发育。磷脂酰肌醇-3,4,5-三磷酸是一种膜脂，可作为多种具有普列克底物蛋白同源（PH）结构域的蛋白质的停靠位点。这类蛋白质是细胞存活、增殖和分化的重要调节因子。RAC-α丝氨酸/苏氨酸蛋白激酶是一种重要的PH结构域蛋白，其活性是植入前胚胎正常发育和存活所必需的。一系列PH结构域蛋白的活性也与胚胎的正常发育有关。本综述批判性地审视了在植入前胚胎自我生成发育过程中，1- O -磷脂酰肌醇3-激酶激活在对胚胎营养因子产生多效性营养反应方面的证据。
