Actively released from cells, exosomes are tiny vesicles (50-150nm diameter) that transport cargo consisting of mRNA, miRNA and proteins, to recipient cells. These can be at a distance from the source of the exosomes which are taken up and their contents released to alter the behaviour of the recipient cells. We have positively identified exosomes in uterine fluid and trapped in mucus contained within this fluid. Exosomes have been prepared from an human endometrial epithelial cell line and been shown to contain select miRNAs, some of which are not detectable in the cells of origin.

We propose that these exosomes play an important role in embryo-maternal communication at implantation.Our current major aims are twofold:

1. To determine the proteome of exosomes derived from endometrial epithelial cells, and how this is altered by the hormone, estrogen and progesterone that drive the menstrual cycle
2. To establish that exosomes are taken up by pre-implantation embryos and that they alter their function. To achieve the latter we will use cell culture models of human implantation in which either mouse embryos or simulated human embryos (spheres of trophectodermal cells) attach to and penetrate polarised layers of human endometrial epithelial cells in culture. Exosome (or exosome-specific cargo miRNA / protein) is expected to alter either or both adhesive or invasive capacity of the trophectodermal cells

Collaborators:

Professor Richard Simpson: La Trobe University
Dr David Greening: La Trobe University
Dr Susan Fisher: University of California, San Francisco, USA