Embryo-uterine interaction coordinates mouse embryogenesis during implantation

Vladyslav Bondarenko, Mikhail Nikolaev, Dimitri Kromm, Roman Belousov, Adrian Wolny, Marloes Blotenburg, Peter Zeller, Saba Rezakhani, Johannes Hugger, Virginie Uhlmann, Lars Hufnagel, Anna Kreshuk, Jan Ellenberg, Alexander van Oudenaarden, Anna Erzberger*, Matthias P. Lutolf*, Takashi Hiiragi*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Embryo implantation into the uterus marks a key transition in mammalian development. In mice, implantation is mediated by the trophoblast and is accompanied by a morphological transition from the blastocyst to the egg cylinder. However, the roles of trophoblast-uterine interactions in embryo morphogenesis during implantation are poorly understood due to inaccessibility in utero and the remaining challenges to recapitulate it ex vivo from the blastocyst. Here, we engineer a uterus-like microenvironment to recapitulate peri-implantation development of the whole mouse embryo ex vivo and reveal essential roles of the physical embryo-uterine interaction. We demonstrate that adhesion between the trophoblast and the uterine matrix is required for in utero-like transition of the blastocyst to the egg cylinder. Modeling the implanting embryo as a wetting droplet links embryo shape dynamics to the underlying changes in trophoblast adhesion and suggests that the adhesion-mediated tension release facilitates egg cylinder formation. Light-sheet live imaging and the experimental control of the engineered uterine geometry and trophoblast velocity uncovers the coordination between trophoblast motility and embryo growth, where the trophoblast delineates space for embryo morphogenesis.

Original languageEnglish
Article numbere113280
Pages (from-to)1-24
Number of pages24
JournalEMBO Journal
Volume42
Issue number17
DOIs
Publication statusPublished - 4 Sept 2023

Keywords

  • biophysical modeling
  • embryo
  • engineering
  • Implantation
  • uterus

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