Doctoral defence: Keerthie Chulanga Dissanayake “Preimplantation embryo-derived extracellular vesicles: potential as an embryo quality marker and their role during the embryo-maternal communication”

On 1 March at 15:00 Keerthie Chulanga Dissanayake will defend his doctoral thesis “Preimplantation embryo-derived extracellular vesicles: potential as an embryo quality marker and their role during the embryo-maternal communication”.

Supervisors:

Professor Alireza Fazeli, University of Tartu
Professor Ülle Jaakma, Estonian University of Life Sciences
Professor Andres Salumets, University of Tartu

Professor Sulev Kõks, University of Tartu

Opponent: 
Richard Lea, University of Nottingham (Great Britain)

Summary
Infertility is a global public health problem that affects millions of people in their reproductive life. Assisted reproductive technologies (ARTs) such as in-vitro fertilization have enabled many patients to overcome this issue. However, a bottleneck in ART success is the implantation failure even after the transfer of morphologically best embryos. Hence, investigations continue to identify better or complementary methods of assessing embryo quality and predicting transfer success, mainly based on the embryo culture media.

Extracellular vesicles (EVs) are membrane-bound nanoparticles released by almost all types of cells under different physiological and pathological conditions. They mediate intercellular communication. Many studies, especially related to cancer, have investigated EVs' potential as biomarkers and therapeutic drug delivery systems.

This project investigated preimplantation embryo-derived extracellular vesicles as a  potential embryo quality marker and a mediator of embryo-maternal communication. Experiments were performed using bovine embryos and human cell-culture based experimental models. The first study showed that individually cultured preimplantation bovine embryos release EVs to their culture media, and their concentration and size profile are dependent on the quality and development stage of embryos. Subsequently, the functionality of preimplantation embryo-derived EVs were tested in the oviduct. It was observed that EVs from good quality embryos, but not the EVs from embryos of low developmental potential quality, could alter the gene expression of the oviduct. Among the up-regulated genes, many were interferon-stimulated genes of the interferon-τ pathway. Interferon-τ is considered the pregnancy recognition molecule in ruminant pregnancy. This finding suggests that the oviduct can serve as a biosensor of embryo quality. Finally, the functional specificity of embryonic EVs were investigated. It was observed that endometrium only react to embryonic EVs but not to the non-embryonic EVs. All these studies support the potential and specificity of embryo-derived EVs as a biomarker of embryo quality.

The defence will take place in Teams.

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