Role of extracellular vesicles in trophoblast invasive migration

The placenta is an essential organ for appropriate foetal development and its successful implantation depends upon invasion of the uterus by trophoblast cells, impacting directly on both animal and human health leading to significant well-being and healthy ageing issues. Epidemiological studies have shown that only around 30% of all conceptions get clinically recognized whilst the majority are lost either spontaneously or during pregnancy complication and that the process of implantation is a key regulator in this process.
Despite the importance of the placenta to foetal development, we know little of the mechanisms that mediate placental implantation - the key step in developing a healthy, functional placenta, but the invasive migration of the trophoblast into the receptive endometrium is paramount. Extracellular vesicle secretion by the trophoblasts themselves has been shown to be important for such regulation. This project will dissect the molecular mechanisms by which the trophoblast cells regulates the receptive environment of the endometrium through the release of extracellular vesicles using an array of cellular biology assays that are routinely used in our laboratories to measure cell motility and invasion, and determine the factors involved in this process.
The project will aim to optimise the best conditions for trophoblasts extracellular vesicles release and cell motility as well as markers for endometrial changes. The second part of the study will provide a full signature of the microvesicles' content through an unbiased mass spectrometry analysis using protocols and approaches that have been conducted within our current BBSRC-funded work. The newly identified markers will be further analysed for their presence in extracellular vesicles and their roles to regulate the trophoblast invasive migration and endometrial function.