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Hydraulic fracturing in embryos

SCIENCE jl

Biologists from the Institut Curie and the CNRS together with a team of physicists from the Centre intedisciplinaire de recherche en biologie (Collège de France/CNRS/Inserm) shed light onto one of the mysteries of mammalian embryonic development.

Did you think hydraulic fracturing would be restricted to gas extraction? You would be wrong! The process does in fact also occur during embryonic development. This surprising finding has just been published by researchers from Institut Curie in Science.

Jean-Léon Maître (CNRS/Institut Curie) and his team of biologists conduct research on mammalian embryos, starting from the very first cell to the development of a whole organism.

In collaboration with a team of theoretical physicists at the Collège de France led by Hervé Turlier, Jean-Léon Maître and his colleagues examined how a liquid-filled cavity, known as the blastocoel, forms within the embryo during pre-implantation development, before attaching to the uterus. A few days after fertilization, when the embryo simply consists of a cluster of cells, a cavity forms within this cluster, pushing some of these cells into a ‘corner’ of the sphere. This step is key, as the position of this cavity plays a decisive role in building the mammalian body plan.

Small water pockets drain into the larger ones to form a single cavity

The researchers then experimented on mouse embryos: “The steps involved in pre-implantation development are very similar in mice and humans, in particular as far as the architecture of the embryo is concerned. The forces that shape these structures are probably the same in both species,” he explains. They used genetically-modified mouse embryos to label the adhesive bonds between cells, which become observable via high-resolution microscopy. As a result, they were able to see that hundreds of microscopic water pockets appeared between the cells, and that those formed by hydraulic fracturing. In other words, water rushes in between the cells, causing the more fragile bonds to break. By creating a hybrid embryo in which some of the cells were less sticky than the others, the researchers were even able to choose where these microcavities would form. Using theoretical modeling, scientists found that the pockets underwent a phenomenon similar to Ostwald ripening: larger pockets drew in the content of smaller pockets, with the latter gradually emptying until a single large cavity remained. This is the same mechanism, which explains the coarsening of bubbles in soapy foams.

This mechanical description of the embryo  illustrates the interdisciplinary nature of this study and the key contribution made by Hervé Turlier’s at the Collège de France. “This research could be used in assisted reproductive techniques (ART). About two-thirds of the transfers of in vitro fertilized embryos fail to implant. Any additional insight into pre-implantation development that we might glean could help us to improve those figures,” says Jean-Léon Maître.

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Hydraulic fracturing and active coarsening position the lumen of the mouse blastocyst