Current knowledge and the future potential of extracellular vesicles in mammalian reproduction.

Extracellular vesicles (EVs), which contain various functional classes of vesicles, namely exosomes, microvesicles, and apoptotic bodies, represent the major nano-shuttle to transfer bioactive molecules from donor to recipient cells to facilitate cell-to-cell communication in the follicular, oviduct, and uterine microenvironments. In addition to transferring various molecular cargos in the form of miRNAs, mRNAs, proteins, lipids, and DNA molecules, the relative proportion of those molecular cargos in the reproductive fluids can be associated with the physiological and pathological condition of the host animal. Inside the follicle, EV-mediated circulation of miRNAs has been reported to be associated with the growth status of the enclosed oocytes, the metabolic status, and the advanced maternal aging of the animal. Importantly, EVs have the potential to protect their cargo molecules from extracellular degradation or modification while travelling to the recipient cells. This fact together with the enormous availability in almost all biological fluids and spent culture media make them attractive in the search for biomarkers of oocyte/embryo developmental competence, receptive maternal environment and a multitude of reproductive pathophysiological conditions. One of the key factors that have contributed to the lower efficiency of assisted reproductive technologies (ART) is the absence of several maternal in vivo factors in the ART procedures. For this, several studies have been conducted to supplement various components present in the follicular and oviductal fluids into the existing ART procedures and significant positive impacts have been observed in terms of embryo cleavage rate, blastocyst rate, resistance to stress, and survival after cryopreservation. The potential of EVs in shuttling protective messages against environmental and physiological stressors has been evidenced. The effective use of the EV-coupled molecular signals against stress-associated conditions has the potential to pave the path for the application of these protective signals against oxidative stress-associated pathological conditions including PCOS, ageing, and endometritis. In this review, we provide current knowledge and potential future use of EVs as remedies in reproductive pathophysiological conditions, mainly in follicular and oviductal microenvironments.