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Intercellular communication is vital to ensure tissue and organism homeostasis and can occur directly, between neighbour cells via gap junctions (GJ), or indirectly, at longer distances, through extracellular vesicles, including exosomes. Exosomes, as intercellular carriers of messenger molecules, mediate the transfer of biological information between donor and acceptor cells. Although the biological effects of exosomes in target cells have been intensively studied, the mechanisms that govern exosomal uptake are not fully understood. Here, we show that Connexin 43 (Cx43), the most widely expressed GJ protein, is present in exosomes in the form of hexameric channels and, more importantly, that exosomal Cx43 is able to modulate the interaction and transfer of information between exosomes and acceptor cells. This study envisions a new paradigm where Cx43-containing channels mediate the release of exosomal content into cells, which constitutes a novel and unanticipated mechanism to modulate intercellular communication.

Knowing that IUGR is associated with altered placental transport, we aimed to characterize the placental transport of folic acid (FA), thiamine (THIAM), serotonin (5-HT), and 1-methyl-4-phenylpyridinium (MPP+) in IUGR. For this, we compared the transport characteristics of (3)H-FA, (3)H-THIAM, (3)H-5-HT, and (3)H-MPP+ in primary cultured human cytotrophoblasts isolated from IUGR and normal placentas (GRTB and NTB cells, respectively) and quantified mRNA expression of several placental transporters, by real-time RT-PCR. Our results show that GRTB cells take up (3)H-FA more efficiently (higher k(in) and A(max) values) and have higher transport capacity (higher V(max) values) for (3)H-FA, (3)H-5-HT, and (3)H-MPP+, when compared with NTB cells. In addition, GRTB cells take up (3)H-THIAM with higher affinity and (3)H-MPP+ with lower affinity than NTB cells. Finally, IUGR placentas have a generalized increase in mRNA expression of FA, THIAM, 5-HT, and MPP+ transporters, when compared with normal placentas, suggesting that the increase in transport capacity may be due to increased expression of placental transporters. These results point to an effect of "compensation for the weakness" of the IUGR placenta and pose the placenta as an active mediator of the communication between maternal and fetal environments.