Human embryonic development: from peri-implantation to gastrulation

Abstract

The basic body plan of the mammalian embryo is established through gastrulation, a pivotal early postimplantation event during which the three major germ layers (endoderm, ectoderm, and mesoderm) are specified with cellular and spatial diversity. Despite its basic and clinical importance, human embryo development from peri-implantation to gastrulation remains shrouded in mystery. Recent advances in the elongated in vitro culture of rodent and non-primate embryos and the construction of embryo-like structures have helped to improve understanding of the mechanisms of human early embryonic development. Here, we review the recent advances and possible future directions in the development of in vitro models to better understand human embryogenesis from peri-implantation to gastrulation. Human embryogenesis from peri-implantation to gastrulation is critical to a healthy birthEarly human embryonic development from peri-implantation to gastrulation has always been a very active yet difficult field of developmental biology (Box 1 and Figure 1A). Errors in this process may lead to adverse pregnancy outcomes, including miscarriage and fetal defects. Understanding the mechanisms underlying early human development is of great importance not only for basic developmental biology but also for regenerative medicine. However, scientists have been puzzling over this Pandora's box because the embryos are hardly accessible. Most of our knowledge about human embryogenesis from peri-implantation to gastrulation is derived from studies on existing anatomical and histological collections of natural human embryos. Lessons from mouse models also enrich our understanding of human embryonic development from a mammalian point of view (Figure 1A,B).Recent progress in the in vitro studies of embryogenesis, including the development of elongated in vitro culture systems for mouse and primate embryos and the construction of stem cell-based embryo models, assisted by single-cell-based multiomic studies and imaging techniques, opens new avenues for studying human embryonic development and has significantly improved our understanding of the characteristics and mechanisms of human embryos from peri-implantation to gastrulation. In this context, it is necessary to provide an overview of these in vitro studies covering their recent progress, limitations, and potential future directions (Figure 1C).

Journey of the mouse primitive endoderm: from specification to maturation

“…As the embryo implants into the uterus, Epi cells orient radially around the proamniotic cavity. Owing to the challenges of retrieving human embryos at these stages, various in vitro models have been devised [183,184]. From in vitro human ES cell differentiation models, it has been suggested that SOX7 and SOX17 are necessary for induction of both VE- and ParE-specific genes [185].…”

Germline stem cells in human

“…In humans, implantation occurs at the end of the blastocyst stage during embryonic day E7–E8. 37 , 38 The inner cell mass splits into the hypoblast, which forms the yolk sac, and the epiblast, which generates the embryo properly. The post-implanted embryo in humans is flat with a bilaminar germ disc, consisting of the epiblast and hypoblast, in addition to the trophoblast, whereas it is cylindrical in mice.…”

“…41 Nevertheless, the CS can loosely be corresponding to days after fertilization or embryonic day. 37,38,[42][43][44] Based on this, the timing of hPGC development is determined (Fig. 2).…”

Glucose-6-Phosphate Dehydrogenase, Redox Homeostasis and Embryogenesis

“…Embryogenesis is a precisely controlled biological process for reprogramming the metabolic state of the cell and driving a single cell to a mature organism [67,68]. Embryogenesis is closely associated with activation and/or repression of genes within a developmental timeline [69,70].…”