O-282 Role of extra-cellular vesicles in reproduction
Authors: Machtinger R 
Published: June 2023

Abstract
Extracellular vesicles (EVs) are bilayer-membrane-bound vesicles isolated from biofluids and tissues. Recently, these organelles have been recognized as a novel mode for inter and intra-cellular communication. The three critical subtypes of EVs include exosomes, microvesicles, and apoptotic bodies. They can be discriminated according to their size, cargo, biogenesis, release pathways, and functions.
These organelles serve as vehicles for transferring bioactive molecules as lipids, proteins, cytokines, and regulatory molecules as RNAs, locally and remotely. A wide range of cell types releases EVs, and their cargo differs under normal and pathological conditions. These facts make them possible biomarkers for diagnosing and treating different medical conditions.
Isolation of EVs from various female and male reproductive tissues such as prostate, epididymis, seminal fluid, fallopian tube, cumulus, and mural granulosa cells, oocytes, embryos at various developmental stages, endometrium, and decidua has been described.
Oogenesis, sperm maturation, fertilization, embryo development, and implantation are composite processes highly reliant on the interaction between tissues and cells. Existing data show that miRNAs and proteins in epididymal fluid associated with testicular maturation are transferred to the sperm by EVs
Ovarian follicular growth is a synchronized process comprising bidirectional communication between the oocyte, cumulus, and mural granulosa cells. Some studies have identified EVs from several species' follicular fluid (FF), including bovine, equine, and human. To date, data linking EVs with oogenesis are primarily descriptive. EV micro-RNA (EV-miRNA) isolated from FF target pathways as mitogen-activated protein kinase (MAPK), wingless signaling pathway (WNT), epidermal growth factor receptor (ErbB), and transforming growth factor beta (TGFß). These pathways are related to folliculogenesis, meiotic resumption, and ovulation.
EV-miRNAs isolated from follicles that contained mature oocytes were associated with fertilization potential and embryo quality. In addition, EVs derived from microvillous-rich oolemma may neutralize acrosome reaction and prevent polyspermy.
Animal and human studies have confirmed that embryos at various developmental stages secrete EVs into the extracellular medium, and embryos internalize EVs. The number, miRNA profile, and size of EVs secreted vary across the cycle and according to embryos’ developmental potential.
Endometrial EVs release miRNAs essential for the blastocyst's adhesion. In ovine, EVs were identified from the uterine lumen and uterine flushing during implantation. Uterine lumen flush EVs were internalized by the trophectoderm cells in the conceptus, reducing trophectoderm cell proliferation.
The study of EVs in reproduction has increased exponentially in the last few years. Evidence support that these organelles contribute to oogenesis, fertilization, embryo development, and implantation. Further research in EVs will help us expand noninvasive methods and identify new biomarkers in the reproductive field.