The human placenta is a fetal organ that is bathed in maternal blood. The surface of the placenta is covered by a single multinucleated cell the syncytiotrophoblast which has a surface area of some 11-13m2 at term. Due to its multinucleated nature the syncytiotrophoblast produces a wider range of extracellular vesicles than most cells. The vesicles extruded from the syncytiotrophoblast include, nano and micro-vesicles that are similar to those from other cells but in addition much larger, multinucleated macrovesicles (also called syncytial nuclear aggregates) are also produced. All of these vesicles are extruded from the syncytiotrophoblast into the maternal blood which deports them around the mother’s body. There is emerging evidence that placental EVs are involved in the major adaptations to the cardiovascular and immune systems that women must complete to undergo normal pregnancy. However it is unclear exactly which maternal organs are targeted by placental EVs.
We examined the distribution of placental EVs in the maternal body using human placental explant-derived fluorescently-labelled macro, micro and nano-vesicles, in pregnant and non-pregnant mice, using a IVS kinetics imager. We also examined the effects of nanovesicles on vascular function using wire myography.
As in women, macrovesicles distributed exclusively to the lungs. The distribution of the smaller vesicles was time and pregnancy status-specific but there was a surprising tropism of the smaller vesicles to the lungs. Responses of resistance vessels to nanovesicles were also dependent on time and pregnancy status.
Within the limits of the systems we used, the distribution of placental micro- and nano-vesicles was somewhat surprising and raises some questions about the relevance of some in vitro experiments. That nano-vesicles from normal placentae affected the tonic function of resistance vessels provides further evidence that placental vesicles may contribute to regulating the normal maternal physiological adaptations to pregnancy.