Society for Reproductive Biology Founders' Lecture 2003.The making of an embryo: short-term goals and long-term implications.

Abstract

During early development, the eutherian mammalian embryo forms a blastocyst comprising an outer trophectoderm epithelium and enclosed inner cell mass (ICM). The short-term goal of blastocyst morphogenesis, including epithelial differentiation and segregation of the ICM, is mainly regulated autonomously and comprises a combination of temporally controlled gene expression, cell polarisation, differentiative cell divisions and cell-cell interactions. This aspect of blastocyst biogenesis is reviewed, focusing, in particular, on the maturation and role of cell adhesion systems. Early embryos are also sensitive to their environment, which can affect their developmental potential in diverse ways and may lead to long-term consequences relating to fetal or postnatal growth and physiology. Some current concepts of embryo-environment interactions, which may impact on future health, are also reviewed.

Tight Junctions in Cell Proliferation

“…Compaction is characterized by the expression and organization of intercellular adhesion and polarization complexes. At a molecular level, protein kinase C isoform alpha (PKCα) and myosin light-chain kinase signaling become activated and maintain cell contact through the regulation of the adherens junction (AJ) proteins E-cadherin, nectin-2, epithin, vezatin, and β-catenin [1,2]. Meanwhile, the membrane-associated guanylate kinase (MAGUK) homolog family member zonula occludens-1 (ZO-1) α - , the smaller splice variant of the two ZO-1α isoforms [3], arrives at the blastocyst membrane cell contact where it binds with the Rab-GTPase, Rab13 [4,5,6].…”

Human Embryonic Stem Cells as a Model for Trophoblast Differentiation

“…Embryo compaction at the morula stage heralds the formation of the blastocyst, with compaction and blastocoel formation requiring the differential expression of tight junctions and Ecadherin, and transport of extraembryonic fluid to form the blastocoel fluid. 1 The cells at the outer surface of the compacting embryo represent the first clearly defined differentiation event in embryonic development-the specification of the trophectoderm (TE). The TE medi-ates attachment of the embryo to the uterine luminal epithelium through mechanisms that are only partly understood 2 due to the severely limited scope of experiments that can be conducted with human embryos.…”

“…An interesting recent development arising from the evaluation of the hESC transcriptome suggested evidence that at least some hESC lines (e.g., H1, H9) share a potential origin with embryonic germ cells, including expression of certain genes such as DAZL and STELLAR 20,21 in early germ cells. Although ESCs are derived from the inner cell mass (ICM) of embryos in which the trophectoderm has been removed by immunosurgery, 9 there is no question that the ICM is a heterogeneous entity, 1 and we are only beginning to formulate an understanding of the biology of the human ICM cells. Further evaluation of additional hESC lines will extend our understanding of the properties and differentiation potential of ESCs and offer insights into the conditions promoting their in vitro differentiation, and its relevance to in vivo development.…”

Understanding cellular disruptions during early embryo development that perturb viability and fetal development

“…Significantly, culture conditions are more than the media formulations; they include all aspects of the system, such as gas phase, macromolecules, pH or visible light . Immediate manifestations of stress include altered homeostasis and perturbed metabolism, which lead to altered cell function and impaired energy production respectively (Leese 1995;Gardner et al 2000;Lane and Gardner 2000b;Thompson et al 2002;Fleming et al 2004). A downstream effect of stress is altered gene function (Gardner and Lane 2005).…”