Project No. 2314

PRIORITY PROJECT

Primary Supervisor

Dr Jane Cleal – University of Southampton

Co-Supervisor(s)

Prof Gary Robinson – University of Kent

Prof Ying Cheong – Complete Fertility University of Southampton

Summary

For successful pregnancy in humans and livestock, the endometrium (the lining of the womb) must create the right environment for the implanting embryo.

This environment is created by endometrial gland secretions, which include extracellular vesicles (ECVs): membrane bound vesicles containing microRNA and proteins that are taken up by target cells to change their function. Using novel 3D ultrastructural imaging approaches, we show that ECVs form on endometrial gland microvilli. We now need to understand how the formation and composition of endometrial ECVs are regulated. The uterine environment has a unique microbiome that interacts with the endometrial cells and is thought to modulate endometrial function and receptivity, however the mechanisms are unclear. Alteration of this microbiota or presence of certain microbiota may effect fertilization and implantation, leading to poor pregnancy outcome.

We therefore need to establish whether the presence of the microbiome and substances it produces can influence the endometrial production of ECVs, be it a pathological effect or a protective response.

Project plan:

1) To characterise endometrial ECVs including their formation, microRNA content and establish whether these change in response to microbial presence and produced substances.

2) To establish whether endometrial ECVs interact with bacterial cells within the endometrial microbiome.

3) To determine whether the endometrial microbiome (from tissue and fluid samples) relates to endometrial phenotypes.

Endometrial gland isolation and 3D imaging approaches are established in Southampton. The teams have expertise in isolation of ECVs, mRNA and microRNA-seq and expertise in bioinformatic analyses.

We routinely collect human endometrial tissue and fluid samples from a range of fertility phenotypes.

The impact of this work will come from improved understanding of the physiological role of ECVs and their regulation, plus the application of these findings to improve the success of natural and assisted conception in humans and livestock breeding programs.