Mechanics of human embryo compaction

Abstract

The shaping of the human embryo begins with compaction, during which cells come into close contact and form a tighter structure. Assisted reproductive technology (ART) studies suggest that human embryos fail compaction primarily because of defective adhesion. Based on our current understanding of animal morphogenesis, other morphogenetic engines, such as cell contractility, could be involved in shaping the human embryo. However, the molecular, cellular and physical mechanisms driving human embryo morphogenesis remain uncharacterized. Using micropipette aspiration on human embryos donated to research, we have mapped cell surface tensions during compaction. This reveals a 4-fold increase of tension at the cell-medium interface while cell-cell contacts keep a steady tension. Comparison between human and mouse reveals qualitatively similar but quantitively different mechanical strategies, with human embryos being mechanically least efficient. Inhibition of cell contractility and cell-cell adhesion in human embryos reveal that only contractility controls the surface tension responsible for compaction. Interestingly, if both cellular processes are required for compaction, they exhibit distinct mechanical signatures when faulty. Analyzing the mechanical signature of naturally failing embryos, we find evidence that non-compacting embryos or partially compacting embryos with excluded cells have defective contractility. Together, our study reveals that an evolutionarily conserved increase in cell contractility is required to generate the forces driving the first morphogenetic movement shaping the human body.

Dissecting the subcellular forces sculpting earlyC. elegansembryos

“…Surprisingly, C. elegans morphogenesis has received little attention, despite its wide-spread use as a model system for genetics and development. Compared to other model systems, such as mouse (Maitre et al, 2016) and human preimplantation embryos (Firmin et al, 2022), drosophila retina (Godard et al, 2020; Hayashi and Carthew, 2004), ascidians (Godard et al, 2020) or frog gastrula (David et al, 2014)), the development and lineage specification in the C. elegans embryo is very rapid. At early stages, the cell cycle lasts only 10-20 minutes and cell type is specified from the 4-cell stage onwards by a combination of asymmetric divisions, rotational movements (Singh and Pohl, 2014; Sugioka and Bowerman, 2018), as well as Wnt (Rocheleau et al) and Notch signaling (Mickey et al, 1996; Thorpe et al, 1997).…”

Ectopic activation of the polar body extrusion pathway triggers cell fragmentation in preimplantation embryos

“…However, in embryos with increased basal contractility and surface tension, the same ectopic activation of the PBE pathway triggers fragmentation (Fig 4 and Fig S3). Interestingly, in a recent study, we measured the surface tension of human embryos and reported tensions 5-10 times higher than for mouse embryos (Firmin et al, 2022). Thus, with unstable spindles and high contractility, human embryos cumulate two features that could synergistically promote fragmentation (Fig 5).…”

Biophysical models of early mammalian embryogenesis

“…Maître et al. numerically simulated the mammalian blastocyst in 3D using a multimaterial mesh-based surface-tracking method ( Maître et al., 2016 ; Da et al., 2014 ; Firmin et al., 2022 ; Turlier and Maître, 2015 ). They hypothesized that compaction and internalization were due to differing contractility between cells, which they implemented using surface tension.…”