Analysis of the mechanisms related in the delivery of miRNA by small extracellular vesicles to COCs and bovine embryos.

Abstract

Although reproductive processes are modulated by endocrine cellular communication mechanisms, recently molecular mechanisms complementary to endocrine ones have been related to reproductive functions. Similar to endocrine hormonal communication, there are molecules important to reproductive processes that act in a paracrine manner carried by extracellular vesicles (EVs). EVs are nanometer-sized vesicles present in several body fluids, including ovarian follicular fluid (FF), oviductal (OF) and uterine fluid, and are involved in cell-cell communication. EVs play an important role mediating the exchange of bioactive materials such as miRNAs, mRNAs and proteins. miRNAs are approximately 20 nucleotides in length and can regulate gene expression by degrading mRNAs or inhibiting their translation. Some transcriptional profiling studies have been conducted to examine gene expression regulation patterns mediated by miRNAs delivered by EVs. However, some gaps still need to be adressed, including the identification of mechanisms involved in the delivery of EVs contents (miRNA and mRNA) to cumulus oocyte complexes (COCs) and developing embryos. In this way, the project aims to answer these gaps and test the hypothesis that EVs from the FF and OF are able to deliver specific miRNAs to the COCs and to bovine embryos in vitro. The main objective is to develop a model to modulate the delivery of bioactive molecules (i.e., miR-21) to COCs and bovine embryos in vitro through EVs from FF and OF carrying active miRNA molecules or their inhibitors. Certainly, this project will identify new tools to enable the use of VEs to deliver specific (miRNA) content and the use of these vesicles for diagnostics based on small fluid volume. Finally, the project will improve our understanding of EV content delivery, which will accelerate the development of a platform of miRNAs and mRNAs suitable to be used as a supplement during IVP and as tools to improve the quality of gametes and embryos used in vitro.