Cell Contraction Shapes Human Embryo Development

Cell compaction is a crucial step in embryo development. Defective compaction prevents the formation of the structure that ensures an embryo can implant in the uterus. This stage is carefully monitored in assisted reproductive technology (ART), which aids in the selection of embryos for implantation.


Previous studies have assumed that a lack of adhesion between cells is the cause of compaction problems. Now, researchers from the Institut Curie have discovered that the contraction of embryonic cells is the driving force behind human embryo compaction.

These findings further our understanding of the mechanisms at play in the early development of embryos and could help improve the success rates of ART. The findings were published in Nature.

The importance of cell compaction in embryo development

 Four days after fertilization, the 8 to 16 cells that compose the embryo move closer together to give the embryo its initial shape. During compaction, cells maximize their cell-cell contact area and minimize their surface exposure to the outside medium.


After in vitro fertilization during ART, embryos that fail to compact entirely or with

delayed compactions show a lower implantation rate upon transfer, illustrating the importance of this process in the further development of the embryo.


“For clinicians observing the development of human embryos in vitro, compaction is the first time they can visually tell that embryos have started developing,” Dr. Jean-Léon Maître, head of the Mechanics of Mammalian Development team at the Institut Curie, told Technology Networks. “When embryos do not compact, clinicians will grade them poorly and are less likely to select them for embryo transfer.”

What is assisted reproductive technology (ART)?

The Centers for Disease Control and Prevention defines ART as all fertility treatments in which either eggs or embryos are handled. This does not include procedures to stimulate egg production. The process typically involves surgically removing eggs from the ovaries, combining them with sperm in the laboratory and returning the fertilized egg to the body.


The research team involved in the study hope that, by improving our understanding of the early stages of human embryonic development, clinicians will be able to refine ART further to improve success rates.

“There are multiple potential avenues where this study could affect concrete practices in ART,” said Maître. “When clinicians find embryos that fail compaction, they could look for issues regarding cell contractility rather than cell adhesion. Multiple compounds are known to affect cell contractility but whether using these compounds in the context of ART is worth it is another story.”

Pre-implantation genetic testing is sometimes offered during ART when one or both genetic parents have, or are carriers of, a known genetic abnormality. Testing is performed on their embryos to determine whether the embryo is at risk of genetic disease. This testing requires harvesting cells from the embryo using a pressurized glass capillary. “Probing the mechanical properties of cells before harvesting them would be very easy for trained clinicians,” explains Maître. This could help with the selection of embryos for testing.

Challenging assumptions about embryonic cell development

Discussing what led the researchers to suspect that other morphogenetic engines were involved in cell compaction Maître said, “There is a mountain of evidence that contractile forces are the main determinant of animal morphogenesis. The past 20 years have shown this first in embryos from invertebrates, then in vertebrates, mammals and finally now in human embryos.”

“It is only because we were confident that our experiments would work that we set to perform experiments on such a rare and precious sample.”

To study the mechanisms at play during compaction, the scientists mapped cell surface tension in human embryonic cells. Using a small glass capillary connected to a microfluidic pump, the researchers applied controlled pressure to the cells and analyzed the amount of pressure required to deform the cells.

From the pressure, we can deduce the surface tension at the surface of cells and, because the technique does not cause any damage to the embryo, we can follow the development of cells and embryos as we continue probing them,” said Maître.


When the embryos correctly develop a stark increase in tension at the surface of the cells is observed. When embryos don’t compact, there is no increase in tension. Additionally, within compacting embryos, some individual cells fail to compact, and these also remain at low tension.  

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The scientists also tested the effects of inhibiting contractility and cell adhesion and analyzed the mechanical signature of embryonic cells with defective contractility. This revealed that, while both cellular processes are required for compaction, only contractility controls the surface tensions responsible for compaction. This mechanism had already been identified in flies, zebrafish and mice, but is a first in humans.

Future outlooks

There are several established techniques to characterize other physical properties of mammalian embryos, such as cell viscosity and pressure inside the embryo cavity. These methods have provided useful information to help uncover the mechanisms underlying the shaping of these embryos. Future studies, according to the researchers, should focus on translating these characterization techniques to human embryonic cells.


Maître concludes, “Most of these studies are performed on mouse embryos but, when we feel confident that experiments can be performed on human embryos with a sufficiently low risk of losing precious samples, we also plan to map the physical properties of human embryos.”

Dr. Jean-Léon Maître was speaking to Blake Forman, Senior Science Writer & Editor for Technology Networks.


About the interviewee:

 

Dr. Jean-Léon Maître is the head of the Mechanics of Mammalian Development team at the Institut Curie. His research focuses on understanding how the mammalian embryo shapes itself studying how the forces that deform the embryo are generated.

 

Reference: Firmin J, Ecker N, Rivet Danon D, et al. Mechanics of human embryo compaction. Nature. 2024. doi: 10.1038/s41586-024-07351-x

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