Embryo‐uterine interaction coordinates mouse embryogenesis during implantation

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 embryouterine 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.

Effects of blastocyst elongation and implantation chamber formation on the alignment of the embryonic axis and uterine axis in mice

“…Several epithelial growth factors (EGFs) and Integrins have been reported as molecules required for implantation ( Fritz et al, 2014 ; Aplin and Ruane, 2017 ). While the heparin-binding EGF-like growth factor (HB-EGF) has been suggested as the earliest molecule that mediates communication between the embryo and LE at the attachment ( Das et al, 1994 ) and ItgB1 may play a role in the invasion of mTE into LE ( Wang et al, 2002 ; Bondarenko et al, 2023 ), we need to examine the exact timing of their expression and function for further study. And many questions remain unanswered, such as the molecular basis of the attachment, the molecular mechanisms underlying the exchange of information between the blastocyst and the LE, and why the IC specifically protrudes toward the AM side.…”

A comprehensive review: synergizing stem cell and embryonic development knowledge in mouse and human integrated stem cell-based embryo models

“…Consequently, various research groups have invested in developing 3D platforms that would mimic the uterine environment. Recently published studies suggest promising outcomes in these 3D platforms ( Gu et al, 2022 ; Ichikawa et al, 2022 ; Bondarenko et al, 2023 ). In one study, it was demonstrated that 11% of retrieved mouse preimplantation embryos developed up to early organogenesis when cultured in a 3D platform ( Gu et al, 2022 ).…”

Confinement modulates axial patterning in regenerating Hydra

“…In vitro , confinement of cultured human embryonic stem cells to micro-patterned adhesive regions was sufficient to drive a self-organized pattern of cell differentiation into the 3 germ layers that arise during gastrulation [27]. More recently, in vitro culturing of mouse embryos using cavities of varying widths, has shown that both the geometry and the stiffness of the confining environment are important in driving and supporting fundamental processes such as axis polarization and cell lineage differentiation [28].…”