Exosomes mediate cell-to-cell communication and induce different effects on target cells depending on the cell origin and exosome content. The function of placental-derived exosomes during normal or pathological pregnancy remains to be established. Delorme-Axfold et al.,, however, recently reported that specific miRNAs are transported in exosome released by trophoblast cells to protect the developing fetus against viral infection. In addition, we have previously reported that exosomes released from cytotrophoblast cells primary culture contain biologically active proteins that can interact with the maternal endothelium and regulate their function. Furthermore, the release of exosome from placental mesenchymal stem cells and cytotrophoblast cells is regulated by the oxygen tension. In this study, we used the PLAP ratio as a measure of the contribution of placental exosomes to total exosomes in maternal blood. We observed that PLAP ratio was similar in both first and second trimesters but decreased dramatically in third trimester. Several factors may contribution to this decrease, including: decreased release of PLAP +ve exosomes from the placenta; decreased circulating half-live of PLAP +ve exosomes; increased released of PLAP-ve exosomes; or a combination of these events. While it is not possible to precisely establish what causes the late gestational decreased in PLAP ratio in this study, the data afford opportunity of further hypothesis testing and, in particular, to establish the clinical utility of PLAP ratio as am indicator of placental function. The release of placental exosomes into maternal blood may result from a change in: the de novo rate of secretion of exosomes; placental mass; placental perfusion; the numbers and/or surface area of syncytotrophoblasts exposed to maternal blood or a combination of these factors. In this study, the concentration of placental exosomes in maternal plasma correlated with placental mass ; and placental perfusion. The association between placental-derived exosomes and placental blood flow was assessed using Doppler velocimetry. Mean uterine pulsatility index declined gradually during pregnancy and strongly correlated with exosomes number and PLAP concentration in maternal blood. Exosomes isolated from peripheral plasma were biologically active, as assessed by their ability to increase endothelial cell migration in vitro. The bioactivity of exosomes was greatest during first trimester and gradually declined with advancing gestational age. This change in bioactivity may reflect a change in the cellular origins, and/or content of exosomes While the role of placental cell-derived exosomes in regulating maternal and/or fetal vascular responses in normal and pathological pregnancies remains to be elucidated, it is tempting to speculate that exosomes released from the syncytitotrophoblast may contribute to maternal vascular adaptation during pregnancy.