Figure 3.

Hypothesized mechanisms on the entrance of fetal/placental miRNAs in the maternal circulation. (a) Connection of the mother and fetus via the placenta. (b) Chorionic villi are responsible for sustaining the placenta with nutrients and oxygen. The intervillus space is filled with maternal blood. (c) Cellular release mechanisms and extracellular transportation systems of miRNAs in accordance with Creemers and colleagues [40]. In the cytoplasm, miRNAs can be incorporated into small vesicles, exosomes, which stem from the endosome, and are released from cells when multivesicular bodies coalesce with the plasma membrane. Microvesicles may also be the source of cytoplasmic miRNAs, which are released from the cell via plasma membrane blebbing. miRNAs are also found in circulation in a microparticle-free form. These miRNAs can be associated with high-density lipoproteins or bound to RNA-binding proteins such as Ago2. It remains unknown as to how these miRNA-protein complexes are released from the cell. They have been suggested to be passively released, as by-products of dead cells, or in an active miRNA-specific manner, via interaction with specific membrane channels or proteins.