Emerging role of extracellular vesicles in communication of preimplantation embryos in vitro

In vitro, efficient communication between mammalian embryos and between embryos and 22 their environment, e.g. maternal somatic cells, implies that there is a sender, a message and a 23 receiver which is able to decode the message. Embryos are secreting a variety of autocrine and 24 paracrine factors, and among those, extracellular vesicles have recently been implicated as 25 putative messengers in embryo-embryo communication and in communication of the embryo 26 with the maternal tract. Extracellular vesicles (EVs) are membrane-bound vesicles, found in 27 biofluids and in culture media conditioned by the presence of embryos or cells, that carry and 28 transfer regulatory molecules, such as microRNAs (miRNAs), messenger RNAs (mRNA), lipids 29 and proteins. 30 Here, we conducted a systematic search of the literature to review and present the currently 31 available evidence on the possible roles of EVs in embryo communication and embryo 32 development. It is important to note that many of the biologically plausible functions of EVs in 33 embryo communication have not yet been substantiated by conclusive experimental evidence. 34 However, indirect evidence, such as the use of media conditioned by embryos or by somatic 35 cells with improved embryo development as a result, may indicate that EVs can be an 36 important asset for the development of tailor-made media allowing better embryo 37 development in vitro, even for single embryo culture.