O-003 Mechanics of human embryo compaction

• Published in: Human reproduction (Oxford) Vol. 38; no. Supplement_1
• Main Authors: Firmin, J, Ecker, N, Rivet-Danon, D, Ozguc, O, Barraud-Lange, V, Turlier, H, Patrat, C, Maitre, J L
• Format: Journal Article
• Language: English
• Published: 22.06.2023
• ISSN: 0268-1161; 1460-2350
• DOI: 10.1093/humrep/dead093.003

Abstract Study question How the human embryo builds the blastocyst is crucial to improve ART, as morphology of human embryo is a prime determinant to assess implantation potential. Summary answer An evolutionarily conserved increase in cell contractility is required to generate the forces driving the compaction, which is the first morphogenetic event shaping the body. What is known already The shaping of the human embryo begins with compaction, during which cells come into close contact and form a tighter structure. 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. Study design, size, duration A total of 54 frozen embryos have been used for this work. The use of human embryos donated for research was allowed by the Agence de la Biomédecine (approval number RE 17-011R) in compliance with the International Society for Stem Cell Research guidelines. Donated embryos were cryopreserved and stored at three different centers in Paris. Embryos were then transferred to the Institut Curie where they were immediately thawed and used for the research project. Participants/materials, setting, methods Using micropipette aspiration on human embryos, we mapped cell surface tensions during compaction. Drug inhibition and immunostaining of cell contractility and cell-cell adhesion in human embryos reveal what drives the surface tension responsible for compaction. To evaluate cell contractility we focused on F-actin and myosin motor proteins, for adhesion we focused on E-cadherin. Main results and the role of chance Mapping cell surface tensions during human compaction reveals a 4-fold increase of tension at the cell-medium interface, from 0.62 ± 0.04 to 2.35 ± 0.08 nN/µm (mean ± SEM of 147 measurements on 10 embryos, Student’s t test p < 10-5), while cell-cell contacts keep a steady tension ∼0.6 nN/µm. Therefore, increased tension at the cell-medium interface drives human embryo compaction, which is qualitatively similar to compaction in mouse embryos (from ∼0.2 to 0.4 nN/µm). Further comparison between human and mouse reveals qualitatively similar but quantitavely different mechanical strategies, with human embryos being mechanically least efficient. Inhibition of cell contractility and cell-cell adhesion in human embryos reveals that, while both cellular processes are required for compaction, adhesion involvement plays a permissive role. Only contractility controls the surface tension responsible for compaction. Interestingly, cell contractility and cell-cell adhesion 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. Limitations, reasons for caution Given the need to use embryos donated to research, which are valuable samples, our sample size is small but sufficient to show statistically significant differences. Moreover, these embryos come from infertile patients undergoing ART. Wider implications of the findings Excluded cells from compaction could be aneuploid to protect the embryonic tissue from chromosomal abnormalities. Is there a correlation between their mechanical signature and the fact that they may be aneuploid remains an open question. How physical laws are used to produce the breathtaking diversity of the shapes of life? Trial registration number ‘not applicable'