Human Pre-gastrulation Development

Abstract

Understanding the progression of early human embryonic development prior to implantation is of fundamental biological importance. Greater insights into early developmental events may lead to clinical improvements, not only via the establishment of novel stem cell models with increased potential or more physiological relevance, but also by uncovering some underlying causes of infertility, miscarriages, and developmental disorders. The majority of human embryos available for study are those donated to research once they are surplus to family building following in vitro fertilization, though in some countries it is also possible to create embryos using donated gametes. As human embryo development is surprisingly inefficient, with only 40% reaching the blastocyst stage in vitro (French, Sabanegh, Goldfarb, & Desai, 2010; Gardner, Lane, Stevens, Schlenker, & Schoolcraft, 2000), many embryos may not develop to a stage suitable for study. Where legally permitted, the oversight of human embryo research is subject to either ethics approval from a local institutional review board (i.e., China and the United States) or both a national regulator as well as a regional research ethics committee (i.e., the United Kingdom). The study of human development has historically been by necessity comparative, relying on model organisms and stem cell lines to inform analyses. Preimplantation mouse and human embryos in particular exhibit remarkably similar gross morphologies at these early stages of development, although key differences have been identified in gene expression patterns and developmental timing. While recent advances in high-resolution transcriptomic analyses at the single cell level have improved our capability to interrogate expression patterns directly in the human embryo, we still lack an understanding of basic molecular events in the human embryo, including how the first cell lineages become specified. Here, we present a current overview of the major developmental events during human preimplantation development, from fertilization to delineation of the embryonic and extraembryonic lineages prior to implantation. Comparisons to both the mouse and alternative models are included where these have formed the basis for similar investigations in a human context.

Keywords: Development; Embryo genome activation; Epiblast; Fertilization; Human; Implantation; Placenta; Pluripotency; Primitive endoderm; Trophectoderm.