Microvesicles provide a mechanism for intercellular communication by embryonic stem cells during embryo implantation.
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.
Department of Molecular Medicine, Cornell University, Ithaca, New York 14853, USA.
Laura M
LM
Desrochers
Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York 14853, USA.
François
F
Bordeleau
Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York 14853, USA.
Cynthia A
CA
Reinhart-King
Department of Molecular Medicine, Cornell University, Ithaca, New York 14853, USA.|Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA.
Richard A
RA
Cerione
Department of Molecular Medicine, Cornell University, Ithaca, New York 14853, USA.
Marc A
MA
Antonyak
D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism; D002450:Cell Communication; D002465:Cell Movement; D055252:Cell-Derived Microparticles / Q000378:metabolism* / Q000648:ultrastructure; D010064:Embryo Implantation; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism* / Q000648:ultrastructure; D005110:Extracellular Space / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D010641:Phenotype; D014327:Trophoblasts / Q000166:cytology
D005353:Fibronectins; D007797:Laminin