Extracellular Vesicles Mediated Early Embryo-Maternal Interactions

Abstract

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.

Keywords: blood circulating exosomes; crosstalk; embryo; endometrium; oviduct; small extracellular vesicles.

Figure 1

Embryo–maternal interactions mediated by extracellular vesicles secreted from the embryo and endometrium cells. Extracellular vesicles secreted by embryos are uptaken by endometrial cells. Extracellular vesicles (EVs) content include miRNA, mRNAs, and proteins that act by paracrine signaling. Different experiments demonstrated that embryo-derived EVs can modulate interferon-tau, apoptosis, cell proliferation, adhesion, angiogenesis, and cell survival biological pathways. Similarly, endometrium cells can secret EVs containing proteins, miRNAs, and mRNAs. These EVs are uptaken by trophoblast cells, and their contents are predicted to regulate interferon-tau production and angiogenesis pathways. However, questions related to how embryo-derived EVs can exit the uterus and arrive in other maternal tissue cells are yet unclear (red interrogation points). Therefore, further studies are needed to understand how the factors secreted by the embryos exit the uterus and to arrive in other maternal tissue, as blood cells, to modulate biological pathways.