4.7 Article

3D biomimetic platform reveals the first interactions of the embryo and the maternal blood vessels

Journal

DEVELOPMENTAL CELL
Volume 56, Issue 23, Pages 3276-+

Publisher

CELL PRESS
DOI: 10.1016/j.devcel.2021.10.014

Keywords

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Funding

  1. German Research Foundation (DFG) Emmy Noether grant [BE 5800/1-1]
  2. German Research Foundation (DFG) Collaborative Research Center 1348 'Dynamic Cellular Interfaces' grant [1348/1]
  3. Cells-In-Motion Cluster of Excellence (CiM) Flexible Funds grant [FF-2017-04]
  4. Collaborative Research Center 1348 'Dynamic Cellular Interfaces' grant [1348/1, AR 732/3-1, AR 732/2-1, SFB850]
  5. Germany's Excellence Strategy [EXC-2189, 390939984]
  6. Leducq Foundation grant
  7. CiM Pilot project grant [PP-2020-10]
  8. International Max Planck Research School-Molecular Biology and Medicine, Munster, Germany

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This study established a 3D biomimetic culture environment mimicking the murine implantation niche, allowing for direct analysis of trophoblast invasion and early interactions with maternal vasculature. The findings reveal that implantation is mediated by collective migration of trophoblast giant cells, which acquire expression of vascular receptors and adhesion molecules to communicate with maternal blood vessels, with Pdgf signaling playing a key role in establishing heterologous contacts.
The process of implantation and the cellular interactions at the embryo-maternal interface are intrinsically difficult to analyze, as the implanting embryo is concealed by the uterine tissues. Therefore, the mechanisms mediating the interconnection of the embryo and the mother are poorly understood. Here, we established a 3D biomimetic culture environment that harbors the key features of the murine implantation niche. This culture system enabled direct analysis of trophoblast invasion and revealed the first embryonic interactions with the maternal vasculature. We found that implantation is mediated by the collective migration of penetrating strands of trophoblast giant cells, which acquire the expression of vascular receptors, ligands, and adhesion molecules, assembling a network for communication with the maternal blood vessels. In particular, Pdgf signaling cues promote the establishment of the heterologous contacts. Together, the biomimetic platform and our findings thereof elucidate the hidden dynamics of the early interactions at the implantation site.

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