Abstract
Studies completed to date provide persuasive evidence that placental cell-derived exosomes play a significant role in intercellular communication pathways that potentially contribute to placentation and development of materno-fetal vascular circulation. The aim of this study was to establish the gestational-age release profile and bioactivity of placental cell-derived exosome in maternal plasma. Plasma samples (n = 20 per pregnant group) were obtained from non-pregnant and pregnant women in the first (FT, 6–12 weeks), second (ST, 22–24 weeks) and third (TT, 32–38 weeks) trimester. The number of exosomes and placental exosome contribution were determined by quantifying immunoreactive exosomal CD63 and placenta-specific marker (PLAP), respectively. The effect of exosomes isolated from FT, ST and TT on endothelial cell migration were established using a real-time, live-cell imaging system (Incucyte). Exosome plasma concentration was more than 50-fold greater in pregnant women than in non-pregnant women (p<0.001). During normal healthy pregnancy, the number of exosomes present in maternal plasma increased significantly with gestational age by more that two-fold (p<0.001). Exosomes isolated from FT, ST and TT increased endothelial cell migration by 1.9±0.1, 1.6±0.2 and 1.3±0.1-fold, respectively compared to the control. Pregnancy is associated with a dramatic increase in the number of exosomes present in plasma and maternal plasma exosomes are bioactive. While the role of placental cell-derived exosome in regulating maternal and/or fetal vascular responses remains to be elucidated, changes in exosome profile may be of clinical utility in the diagnosis of placental dysfunction.
Highlights
The placenta plays a pivotal role in orchestrating maternal adaptation to pregnancy and synthesises and releases pregnancyassociated autacoids that influence fetal, placental and maternal metabolism [1]
Studies completed to date provide persuasive evidence that placental cell-derived exosomes play a significant role in intercellular communication pathways that potentially contribute to placentation and development of maternal-fetal vascular exchange
The data obtained in this study establish, that pregnancy is associated with a 50-fold increase in the concentration of exosomes in maternal plasma
Summary
The placenta plays a pivotal role in orchestrating maternal adaptation to pregnancy and synthesises and releases pregnancyassociated autacoids that influence fetal, placental and maternal metabolism [1]. Exosomes are cell-derived bioactive vesicles, secreted by exocytosis and reflect aspects of the physiological state and function of the originating cells, including the human placenta [5,6]. Exosomes regulate intracellular pathways by sequestering signalling molecules from the cytoplasm by reducing their bioavailability or preventing their packaging and release via exocytosis.[9]. They contain mRNA, miRNA [10], cellsurface receptors [11] and protein mediators [12] that can interact with either adjacent or distal cells to reprogram their phenotype and regulate cell function [13]. Available data suggest that the release of exosomes represents an important and common mode of cell-to-cell communication [14] under both normal and pathological conditions [15,16]
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