The Biological Function of Extracellular Vesicles during Fertilization, Early Embryo—Maternal Crosstalk and Their Involvement in Reproduction: Review and Overview

Abstract

Secretory extracellular vesicles (EVs) are membrane-enclosed microparticles that mediate cell to cell communication in proximity to, or distant from, the cell of origin. Cells release a heterogeneous spectrum of EVs depending on their physiologic and metabolic state. Extracellular vesicles are generally classified as either exosomes or microvesicles depending on their size and biogenesis. Extracellular vesicles mediate temporal and spatial interaction during many events in sexual reproduction and supporting embryo-maternal dialogue. Although many omic technologies provide detailed understanding of the molecular cargo of EVs, the difficulty in obtaining populations of homogeneous EVs makes difficult to interpret the molecular profile of the molecules derived from a miscellaneous EV population. Notwithstanding, molecular characterization of EVs isolated in physiological and pathological conditions may increase our understanding of reproductive and obstetric diseases and assist the search for potential non-invasive biomarkers. Moreover, a more precise vision of the cocktail of biomolecules inside the EVs mediating communication between the embryo and mother could provide new insights to optimize the therapeutic action and safety of EV use.

The Proteome of Equine Oviductal Fluid Varies Before and After Ovulation: A Comparative Study

“…among the 691 unique proteins recognized for E. caballus, 375 (54.3%) were associated with the extracellular exosome category (GO:0070062). Hence, the majority of the identified proteins in equine OF may be involved in cell-to-cell communication as the identified protein cargo may be delivered from the oviductal milieu to the gametes/embryos in membrane-enclosed microparticles, as also demonstrated in other species (18,26). The second category obtained in the enrichment analysis was cytoplasm (GO:0005737; 200 identified proteins), which corresponds with 28.9% of all the identified proteins, as also described in other species in which 13-27% of all the identified proteins were shown to have a cytoplasmic origin (18).…”

Amino Acid Transport and Metabolism Regulate Early Embryo Development: Species Differences, Clinical Significance, and Evolutionary Implications

“…Redundant mechanisms exist, however, to resist the otherwise detrimental effects of the hypertonic oviductal fluid, since insulin-like growth factors [36] as well as other embryos nearby [2] foster preimplantation embryo development in hyperosmotic media. Nearby embryos promote development apparently via paracrine signaling [2], that may include the production of extracellular vesicles by the conceptuses [37]. All these mechanisms are likely present in vivo to promote the development of healthy embryos and subsequently adults.…”

“…A suppression of system B 0,+ activity may occur in blastocysts owing to the inhibition of the system by extracellular histones in uterine secretions [9,19,39]. It remains to be determined whether these histones are free in uterine secretions or sequestered in extracellular vesicles produced by uterine epithelial or other cells, e.g., [37,40]. Regardless of their origin, such actions of the histones must somehow be neutralized at the time of implantation [9,19,39].…”

Extracellular vesicles from maternal uterine cells exposed to risk factors cause fetal inflammatory response

“…EVs are circular vesicles that are surrounded by a lipid bilayer, lack nuclei and cannot replicate [9]. EVs are released by both maternal and fetal cells and carry various cargo that are reflections of the physiologic and metabolic state of the cells at the time of their release [10]. EV cargo contents can be taken up by recipient cells to induce specific functional effects [11].…”