Microvesicles provide a mechanism for intercellular communication by embryonic stem cells during embryo implantation

Nat Commun. 2016 Jun 15;7:11958. doi: 10.1038/ncomms11958.

Abstract

Communication between the inner cell mass (ICM) and the trophoblast layer of the blastocyst is known to occur, but its functional consequences on early developmental events is unclear. Here we demonstrate that embryonic stem (ES) cells derived from the ICM generate and shed microvesicles (MVs), a major class of extracellular vesicles (EVs), which influence trophoblast behaviour during the implantation process. The MV cargo proteins laminin and fibronectin interact with integrins along the surfaces of the trophoblasts, triggering the activation of two signalling kinases, JNK and FAK, and stimulating trophoblast migration. We further show that injecting MVs isolated from ES cells into blastocysts results in an increase in their implantation efficiency. Thus, these findings highlight a unique mechanism by which ES cells communicate with trophoblasts within the blastocyst to increase their ability to migrate into the uterus, thereby promoting one of the earliest and most important steps during pregnancy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blastocyst / cytology
  • Blastocyst / metabolism
  • Cell Communication*
  • Cell Movement
  • Cell-Derived Microparticles / metabolism*
  • Cell-Derived Microparticles / ultrastructure
  • Embryo Implantation*
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / metabolism*
  • Embryonic Stem Cells / ultrastructure
  • Extracellular Space / metabolism*
  • Fibronectins / metabolism
  • Laminin / metabolism
  • Mice
  • Models, Biological
  • Phenotype
  • Trophoblasts / cytology

Substances

  • Fibronectins
  • Laminin