Embryo-maternal communication: extracellular vesicles role in mediating trophoblast-endometrial interactions

In the last two decades, growing interest in extracellular vesicle (EVs) related research has been observed. EVs, a cell secreted vesicle, have been reported to be found in biological fluids such as saliva, plasma, urine, amniotic fluid, semen, follicular fluid and breast milk. They are believed to act as a messenger for cell to cell communication that contributes to a specific role in body function. The interesting fact about EVs are the cargoes that they carry which includes protein, miRNA, lipid, DNA and other RNA moieties. There is an increasing number of promising pieces of evidence relating EVs to the field of reproduction. However, the role of EVs in mediating embryo-maternal communication especially during trophoblast-endometrial interactions is still unclear. Furthermore, implantation failure has been reported to be contributing to 2/3 of the reproductive defect and this issue needs more attention to be able to improve the outcomes of the assisted reproductive technologies (ART). Therefore, this thesis is dedicated to investigate the role of EVs in mediating embryo-endometrial communication.

Since research on EVs and embryo-maternal communication is a relatively new field to be explored, with the absence of a standard in vitro model of implantation, optimisation of the 3D in vitro model of embryo-maternal communication is required to further discover and understand the functional and molecular processes involved in the implantation process. Studies reported during the course of this thesis showed the effects of EVs biogenesis inhibition on trophoblast and endometrial cells and demonstrated their effect on trophoblast-endometrial binding/implantation rate. Further investigation of the EVs physical, biochemical and proteomic properties revealed significant differences in the EVs-derived from different cell culture systems. These findings suggest the importance of proper in vitro model design and cell selection to mimic the in vivo environment to further explore the role of EVs in embryo-maternal interaction. Breakdown in these processes of communication may lead to implantation failure and/or miscarriage. Hence, further elucidation of the molecular and cellular pathways in which EVs play a role are required for enhancement of diagnostic and therapeutic approaches in ART.

As the impact of the pandemic, the present study was not able to be completed as planned however, within the limited time and resources available, a full description of all the experimental work conducted with exciting findings is presented in this thesis.