Associated changes in the concentration and bioactivity of exosomes present in maternal peripheral plasma. The data obtained in this study establish, that pregnancy is associated with a 50-fold increase in the concentration of exosomes in maternal plasma. In a longitudinal study, the concentration of placental exosomes in plasma increased during pregnancy and correlated with mean uterine artery blood flow. At delivery, plasma concentration of placental exosomes correlated with placental weight. The study further established that exosomes present in maternal plasma are bioactive and promote cell migration. These data clearly establish that normal healthy pregnancy is characterised by the release of bioactive exosomes into maternal blood from as early as 6 weeks of gestation and that the concentration of placenta-specific exosomes is information of placental perfusion and growth. This study provides proof-ofprinciple and baseline data that may facilitate the early identification of dysfunctional placentation. In this study, exosomes were isolated using differential and buoyant density centrifugation to obtain enriched exosome population. Nanovesicles isolated using this method, displayed a diameter between,40-120 a buoyant density on sucrose gradient of 1.21–1.192 g/m and were positive for the exosome markers, CD63, CD9 and CD81. These data are characteristic of exosomes and consistent with previously published data. The data obtained in this study establish that pregnancy is associated with a dramatic increase in the number of exosomes circulating in maternal blood. The concentration of exosomal protein in first trimester plasma was 50-fold greater than that observed in non-pregnant women. Maternal plasma exosomal protein concentrations increased a further two-fold during pregnancy, to be 100-fold greater than non-pregnant values. Exosomes present in maternal plasma may be derived from either maternal and/or fetal origin. To address this question, plasma exosomes were further characterised by the presence of a syncytiotrophoblast-specific marker. PLAP was not detectable in the exosomal fraction from non-pregnant plasma and is consistent with previously published data. Plasma exosomal PLAP displayed a similar gestational age profile to that observed for exosome number and was significantly correlated with exosomal protein and CD63 at delivery. The syncytiotrophblast is in direct contact with maternal blood and, with a surface area of. 10 m2, it represents a significant source of placenta vesicular membrane entering maternal blood. More that 3 g of syncytiotrophblast-derived membrane is released each day near term. The contribution of syncytiotrophblastderived exosomes to total syncytiotrophblast membrane released, however, is not known. Similarly, no quantitative estimates of the contribution of syncytiotrophblast-derived exosomes to total maternal plasma exosomes remains to be established.