Embryo-maternal crosstalk is an important event that involves many biological processes, which must occur perfectly for pregnancy success. This complex communication starts from the zygote stage within the oviduct and continues in the uterus up to the end of pregnancy. Small extracellular vesicles (EVs) are part of this communication and carry bioactive molecules such as proteins, lipids, mRNA, and miRNA. Small EVs are present in the oviductal and uterine fluid and have important functions during fertilization and early embryonic development. Embryonic cells are able to uptake oviductal and endometrium-derived small EVs. Conversely, embryo-derived EVs might modulate oviductal and uterine function. In this review, our aim is to demonstrate the role of extracellular vesicles modulating embryo-maternal interactions during early pregnancy.2 of 15 luteotrophic and anti-luteolytic actions, guaranteeing the corpus luteum (CL)'s capability to secrete the progesterone necessary to establish and sustain pregnancy [15,16]. Additionally, different biological molecules are secreted by the embryos of several mammalian species during MRP as interferon-tau (IFNT) in ruminant [17], estradiol in pigs [18], and chorionic gonadotropin in humans [19]. However, recent reports indicate that the embryo is also able to secrete EVs [20][21][22], but their role in MRP is still elusive.Therefore, in mammals, the embryos and the female tract (oviduct and endometrium) are able to secrete extracellular vesicles during the pre-implantation period. Extracellular vesicles are cell-secreted vesicles that are classified according the their size, biogenesis, and secretion, as exosomes, microvesicles, and apoptotic bodies [23]. Several cellular types can secrete EVs including follicular [24,25], oviductal, and endometrial cells [13,21,26], as well as in vitro and in vivo produced embryos [20][21][22]27]. Extracellular vesicles carry bioactive molecule as miRNAs, mRNAs [28], proteins [29], and lipids [30], which modulate various reproductive processes such as ovarian follicular development, oocyte maturation, embryonic development, maternal-embryonic communication, and the establishment of mammalian gestation. There is experimental evidence that EVs participate in intercellular communication in essential reproductive events related to the establishment of pregnancy, such as cell proliferation, crosstalk between the maternal organism and conceptus, as well as during embryonic implantation [31]. In early stages of pregnancy, the communication between the conceptus and maternal organism is necessary and the evidence of the participation of EVs of maternal or embryonic origin is increasing [14].Herein, we will review the current knowledge on embryo-maternal interactions, with special emphasis on the roles of EVs during the early crosstalk between embryonic and maternal tissues.Int. J. Mol. Sci. 2020, 21, 1163 3 of 15 (reviewed by [47]). PGE2 secreted by equine viable embryos during early embryonic development is involved with the initial oviductal transpo...