Unlocking a Decade of Research on Embryo-Derived Extracellular Vesicles: Discoveries Made and Paths Ahead.

Abstract

Over the past decade, research on embryo-derived extracellular vesicles (EVs) has unveiled their critical roles in embryonic development and intercellular communication. EVs secreted by embryos are nanoscale lipid bilayer vesicles that carry bioactive cargo, including proteins, lipids, RNAs, and DNAs, reflecting the physiological state of the source cells. These vesicles facilitate paracrine and autocrine signaling, influencing key processes such as cell differentiation, embryo viability, and endometrial receptivity. Studies reveal that EVs can traverse the zona pellucida, transferring molecular signals that enhance blastocyst formation and support embryo-maternal crosstalk. EVs have emerged as non-invasive biomarkers for embryo quality, with their cargo providing insights into genetic integrity and developmental competence. Advances in isolation and characterization techniques have identified specific microRNA (miRNAs) and transcription factors within EVs, offering potential for use in preimplantation genetic screening (PGS) and sex determination. Moreover, EV-mediated interactions with the maternal environment are critical for successful implantation, as they modulate gene expression and immune responses in endometrial and oviductal cells. Despite these advancements, challenges persist, including the standardization of EV isolation methods and the low yield of EVs DNA from spent culture media. Future research should aim to refine analytical techniques, explore EV-miRNA profiling, and investigate the mechanisms underlying EV-mediated signaling. By addressing these gaps, EVs could revolutionize embryo selection and reproductive technologies, offering new strategies to improve outcomes in assisted reproduction and animal breeding.