Abstract
Membrane-bound extracellular vesicles (EVs) mediate intercellular communication in all organisms, and those produced by placental mammals have become increasingly recognized as significant mediators of fetal-maternal communication. Here, we aimed to identify maternal cells targeted by placental EVs and elucidate the mechanisms by which they traffic to these cells. Exogenously administered pregnancy-associated EVs traffic specifically to the lung; further, placental EVs associate with lung interstitial macrophages and liver Kupffer cells in an integrin-dependent manner. Localization of EV to maternal lungs was confirmed in unmanipulated pregnancy using a transgenic reporter mouse model, which also provided in situ and in vitro evidence that fetally-derived EVs, rarely, may cause genetic alteration of maternal cells. These results provide for the first time direct in vivo evidence that placental EVs target maternal immune cells, and further, that EVs can alter cellular phenotype.
Highlights
Membrane-bound extracellular vesicles (EVs) mediate intercellular communication in all organisms, and those produced by placental mammals have become increasingly recognized as significant mediators of fetal-maternal communication
As placental EVs are a likely source of this increase, and as they can potentially access all maternal organs via the vasculature, we tested the specificity of their trafficking by comparing localization of plasma EVs from nonpregnant and pregnant mice
We show that placental EVs traffic to the lung and the liver
Summary
Membrane-bound extracellular vesicles (EVs) mediate intercellular communication in all organisms, and those produced by placental mammals have become increasingly recognized as significant mediators of fetal-maternal communication. Exosomes are 40–150 nm membrane-enclosed EVs created by the invagination of early endosomes to form multivesicular bodies, which can fuse with either the lysosome or the plasma membrane When they fuse with the plasma membrane, the intraluminal vesicles are released from the cell as exosomes, carrying bioactive nucleic acids, proteins, and lipids through interstitial space and the circulation to distant c ells[2]. Among mammalian cells and tissues that shed vesicles, the placenta plays a important role, releasing enormous quantities of EVs in order to communicate with local and distant maternal cells during pregnancy. This is true of hemochorial species, in which the maternal–fetal interface consists of trophoblast cells that contact maternal blood. We provide in vivo and in vitro proof of principle that genetic alteration of maternal cells by placenta-derived exosomes is possible
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