Doctoral defence: Mohammad Mehedi Hasan “Characterization of follicular fluid derived extracellular vesicles and their contribution to periconception environment”

On 17 October at 15:00 Mohammad Mehedi Hasan will defend his doctoral thesis “Characterization of follicular fluid derived extracellular vesicles and their contribution to periconception environment”.

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

Opponent:
Professor Gregory Lavieu, University of Paris (France)

Summary
The prevalence of infertility is one of the most pressing issues in today’s society. Based on forecasts from the World Health Organization, infertility will rank third among the most serious global health problems in the twenty-first century, after cancer and cardiovascular disease. Assisted reproductive technology (ART), which includes in-vitro fertilization (IVF), is an essential therapeutic method for the treatment of infertility. However, the success rate of ART is still not up to the mark and there is abundant room for improvement in ART's. One of the main reasons hindering the success of ART’s could be the failure to enhance the quality of gametes, and undermining the factors present during preconception. Therefore, the current research identifies the bottleneck issues of infertility, methods for gametes improvement, and role of follicular fluid (FF) derived extracellular vesicles (EVs) in enhancing a suitable preconception environment that might be essential for fertilization and early embryo development.

In recent years, EVs (membrane-bound nanosized particles) have become increasingly recognized as an alternative mode of intercellular communication. Many published studies have shown that EVs had been isolated from nearly every type of biological fluid, including FF. FF-derived EVs are essential for oocyte maturation, fertilization, embryo development and have potential to act as biomarkers.

In this project, we investigated the role of FF EVs in regulating the gene expression of oviduct, its impact on vital functions of spermatozoa, and the cargo changes in FF derived EVs in Polycystic ovarian syndrome (PCOS) patients versus healthy people. Our first study showed that bovine FF and FF EVs alter the gene expression of bovine oviductal epithelial cells, which may contribute to the preparation of preconception microenvironment, fertilization and early embryo development. Similarly, our second study showed that bovine FF EVs enhances the functional properties of bovine spermatozoa, specifically viability, capacitation, and acrosome reaction. Finally, our third study showed EV cargo changes in different pathophysiological condition (PCOS and fertile women) and their contribution to ovarian signal disturbance. The miRNAs analysis revealed that FF EVs derived from PCOS women carry different miRNAs as compared to healthy women. Our results also confirmed novel miRNA derived from FF EVs in case of PCOS women, which could use as a potential biomarker for PCOS diagnosis. In conclusion, our studies overall findings confirmed the presence of EVs in FF and their effects on spermatozoa, and oviductal gene expression, and differences in cargo of FF EVs in case of PCOS patients versus healthy women.