Fluid transport properties dominate blastocyst expansion over mechanics
Year: 2026
Type: preprint
Abstract: Lumens populate most of our organs and their size, which dynamically changes throughout the day and lifetime, can influence their function. During mammalian development, the first lumen appears in the blastocyst. Surface epithelial cells pump ions to build an osmotic gradient that draws water, which inflates the embryo and stretches the epithelium as well as the zona pellucida, an elastic shell protecting the embryo. Blastocyst expansion is not steady and instead undergoes cycles of expansion interrupted by collapses during which the lumen leaks out. Early studies identified the critical role of osmotic pressure difference in regulating the expansion of the blastocyst whereas recent studies proposed that mechanical stresses would set the size of the embryo. However, the relative contributions of osmotic and mechanical stresses to lumen expansion dynamics remain unclear. Here, we investigate this using microfluidics, biophysics, machine learning and modelling on mouse embryos. Breaking down the expansion dynamics of mouse embryos, we discovered that fluid pumping rate accelerates, compensating for the increased frequency of collapses interrupting episodes of expansion. We reasoned that fluid transport could be rate limited by osmotic pumping, water permeability and/or mechanical constraints. Removing the mechanical constraint from the zona pellucida only marginally affected these expansion dynamics. Forcing fluid exchange with osmotic shocks we measured that water permeability is large enough not to restrict fluid accumulation rates. Finally, we estimate ion pumping for mouse blastocysts and interfere with it using inhibitors to measure how it quantitatively sets blastocyst expansion rates. T£ogether, we propose that osmotic pressure differences, regulated by fluid transport properties, dominate over mechanical stresses in controlling blastocyst expansion dynamics.
Institutions: Centre National de la Recherche Scientifique, Inserm, Université Paris Sciences et Lettres, Sorbonne Université, Institut Pierre-Gilles de Gennes pour la Microfluidique, Physique des Cellules et Cancers, Génétique et biologie du développement, Institut Curie, École Polytechnique, Institut Polytechnique de Paris, Laboratoire d'Optique et Biosciences
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7221100590