Placental Extracellular Vesicles and Feto-Maternal Communication

Abstract

The human placenta is an anatomically unique structure that extrudes a variety of extracellular vesicles into the maternal blood (including syncytial nuclear aggregates, microvesicles, and nanovesicles). Large quantities of extracellular vesicles are produced by the placenta in both healthy and diseased pregnancies. Since their first description more than 120 years ago, placental extracellular vesicles are only now being recognized as important carriers for proteins, lipids, and nucleic acids, which may play a crucial role in feto-maternal communication. Here, we summarize the current literature on the cargos of placental extracellular vesicles and the known effects of such vesicles on maternal cells/systems, especially those of the maternal immune and vascular systems.T he placenta is an unusual organ with a short and defined life span. The human placenta is a fetal organ that sits between the fetus and its mother, connecting the fetus to the maternal blood supply. It is highly invasive and the entire surface of the placenta is in contact with the maternal circulation during most of gestation. Therefore, the human placenta effectively behaves as one wall of a maternal "blood vessel." This phenomenon is quite remarkable because, being a fetal organ, the placenta is in essence a semiallogeneic tissue graft in normal pregnancy and a complete allograft in surrogate or donor egg pregnancies. Therefore, the placenta is nature's only tissue graft.The human placenta has a villous (branching) structure. The surface of placental villi is covered by the multinucleated syncytiotrophoblast that is terminally differentiated and is not mitotically active. The growth and replenishment of the syncytiotrophoblast is effected by fusion of underlying mononuclear cytotrophoblasts into this layer. Beneath the cytotrophoblasts is the mesenchymal core of the villus with fetal blood vessels. The syncytiotrophoblast is a remarkable cell, which at least in theory, is a single cell covering the entire surface of the placenta and is the immunological barrier between the maternal immune system and the fetus. In a normal term placenta, the syncytiotrophoblast has an area of some 11 -13 m 2 (Mayhew 2014). However, the syncytiotrophoblast can be denuded, leaving areas lined by fibrinoid rather than syncytiotrophoblast and presumably before the laying down of this fibrinoid, cells of the villous mesenchymal core or cytotrophoblasts are exposed to the maternal blood, at least temporarily.

Differential patterning of genes involved in serotonin metabolism and transport in extra-embryonic tissues of the mouse

“…Although it could result from 5-HT packaging into large vesicles, only a very low level of Vmat2 expression was observed in the placenta and co-localized with Ctsq . Protein and miRNA packed exosomes and microvesicles have been shown to be released from placenta into the maternal blood [38,39]. The results suggest that 5-HT may also be packed into placental microvesicles, possibly to facilitate transport to the fetus.…”

Placenta-derived extracellular vesicles: their cargo and possible functions

“…Recently, Tong and Chamley (2015) have suggested the maternal-fetal interface extends beyond these areas described above because the large surface area of syncytiotrophoblast releases 'trophoblast debris' that is also capable of releasing extracellular vesicles into the maternal circulation throughout pregnancy. Extracellular vesicles may play important physiological roles in the mother during pregnancy and may contribute to the pathophysiology evident during pre-eclampsia and other pregnancy-related conditions.…”

Isolation of human trophoblastic extracellular vesicles and characterization of their cargo and antiviral activity

“…In contrast, the transmission of trophoblastic biological signals into the fetal circulation may require trafficking through the villous basal membrane and fetal endothelial cells before entering the fetal circulation. In addition to hormones, growth factors, and other signaling proteins and akin to other epithelial cells, trophoblasts release a diverse repertoire of lipid-encapsulated extracellular vesicles (EVs) into the maternal blood, including apoptotic cell-derived EVs (ABs), microvesicles (MVs), and exosomes (EXs) [1–4]. The size of ABs ranges between 1~5 µm, and are produced by deportation of trophoblastic fragments during apoptosis [5].…”