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

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.

SUBMITTER: Desrochers LM

PROVIDER: S-EPMC4912619 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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

Desrochers Laura M LM Bordeleau François F Reinhart-King Cynthia A CA Cerione Richard A RA Antonyak Marc A MA

Nature communications 20160615

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 surfac ...[more]

PMID: 27302045

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Project description:Exosomes are nanoparticles (∼100 nm diameter) released from cells, which can transfer small RNAs and mRNA via the extracellular environment to cells at distant sites. We hypothesised that exosomes or the slightly larger microvesicles (100-300 nm) are released from the endometrial epithelium into the uterine cavity, and that these contain specific micro (mi)RNA that could be transferred to either the trophectodermal cells of the blastocyst or to endometrial epithelial cells, to promote implantation. The aim of this study was to specifically identify and characterise exosomes/microvesicles (mv) released from endometrial epithelial cells and to determine whether exosomes/mv are present in uterine fluid. Immunostaining demonstrated that the tetraspanins, CD9 and CD63 used as cell surface markers of exosomes are present on the apical surfaces of endometrial epithelial cells in tissue sections taken across the menstrual cycle: CD63 showed cyclical regulation. Exosome/mv pellets were prepared from culture medium of endometrial epithelial cell (ECC1 cells) and from uterine fluid and its associated mucus by sequential ultracentifugation. Exosomes/mv were positively identified in all preparations by FACS and immunofluorescence staining following exosome binding to beads. Size particle analysis confirmed the predominance of particles of 50-150 nm in each of these fluids. MiRNA analysis of the ECC1 cells and their exosomes/mv demonstrated sorting of miRNA into exosomes/mv: 13 of the 227 miRNA were specific to exosomes/mv, while a further 5 were not present in these. The most abundant miRNA in exosomes/mv were hsa-miR-200c, hsa-miR-17 and hsa-miR-106a. Bioinformatic analysis showed that the exosome/mv-specific miRNAs have potential targets in biological pathways highly relevant for embryo implantation. Thus exosomes/mv containing specific miRNA are present in the microenvironment in which embryo implantation occurs and may contribute to the endometrial-embryo cross talk essential for this process.

Dataset Information

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

Publications

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

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