Morphogenesis of the human preimplantation embryo: bringing mechanics to the clinics

Abstract

During preimplantation development, the human embryo forms the blastocyst, the structure enabling uterine implantation. The blastocyst consists of an epithelial envelope, the trophectoderm, encompassing a fluid-filled lumen, the blastocoel, and a cluster of pluripotent stem cells, the inner cell mass. This specific architecture is crucial for the implantation and further development of the human embryo. Furthermore, the morphology of the human embryo is a prime determinant for clinicians to assess the implantation potential of in vitro fertilized human embryos, which constitutes a key aspect of assisted reproduction technology.Therefore, it is crucial to understand how the human embryo builds the blastocyst. As any material, the human embryo changes shape under the action of forces. Here, we review recent advances in our understanding of the mechanical forces shaping the blastocyst. We discuss the cellular processes responsible for generating morphogenetic forces that were studied mostly in the mouse and review the literature on human embryos to see which of them may be conserved. Based on the specific morphological defects commonly observed in clinics during human preimplantation development, we discuss how mechanical forces and their underlying cellular processes may be affected. Together, we propose that bringing tissue mechanics to the clinics will advance our understanding of human preimplantation development, as well as our ability to help infertile couples to have babies.

Mechanics of human embryo compaction

“… The shaping of the human embryo begins with compaction, during which cells come into close contact and form a tighter structure 1,2 . Assisted reproductive technology (ART) studies suggest that human embryos fail compaction primarily because of defective adhesion 3,4 .…”

“…Therefore, our appreciation of how the human body shapes itself during embryonic development rarely comes from studies on human embryos themselves, but instead relies mostly on the extrapolation from findings in other species and, more recently, from engineered human embryo models 7,8 . For example, we still do not know whether contractility of the actomyosin cortex, a major morphogenetic engine during animal development 5,6,9 , plays a similarly important role during human morphogenesis 1 . Opportunely, preimplantation development constitutes a unique setting to carry out experimentations on live embryos and can provide both validation and breakthrough in our understanding of human embryonic development 10–13 .…”

“…Human morphogenesis begins with compaction on the 4 th day after fertilization, when the embryo is composed of 8 to 16 cells 1–3,14 . After in vitro fertilization (IVF) during ART, embryos failing to compact entirely or with a delayed compaction show lower implantation rate upon transfer 15–17 , illustrating the importance of this process for further development.…”

“…Interestingly, loss of contractility and adhesion results in distinct mechanical signatures (Fig 2i): low γ cm and γ cc with ML7 medium in contrast to high γ cm and γ cc with EDTA medium. Therefore, mechanical signatures could be used to distinguish which cellular process fails when compaction is defective and potentially help diagnostics in IVF clinics 1,25 .…”

“…Another compaction defect that is commonly observed is partial compaction, where some of the blastomeres do not participate in the compacted mass 1,3,4 . Such excluded cells are thought to be either eliminated from the blastocyst or could participate to extra- embryonic tissues such as the trophectoderm that forms at the surface of the embryo 1,2,27 .…”