TY - JOUR
T1 - Placental exosomes during gestation
T2 - Liquid biopsies carrying signals for the regulation of human parturition
AU - Salomon, Carlos
AU - Nuzhat, Zarin
AU - Dixon, Christopher L.
AU - Menon, Ramkumar
N1 - Publisher Copyright:
© 2018 Bentham Science Publishers.
PY - 2018
Y1 - 2018
N2 - Parturition is defined as the action or process of giving birth to offspring. Normal term human parturition ensues following the maturation of fetal organ systems typically between 37 and 40 weeks of gestation. Our conventional understanding of how parturition initiation is signaled revolves around feto-maternal immune and endocrine changes occurring in the intrauterine cavity. These changes in turn correlate with the sequence of fetal growth and development. These important physiological changes also result in homeostatic imbalances which result in heightened inflammatory signaling. This disrupts the maintenance of pregnancy, thus leading to labor-related changes. However, the precise mechanisms of the signaling cascades that lead to the initiation of parturition remain unclear, although exosomes may be a mediator of this process. Exosomes are a subtype of extracellular vesicles characterised by their endocytic origin. This involves the trafficking of intraluminal vesicles into multivesicular bodies (MVB) and then exocytosis via the plasmatic membranes. Exosomes are highly stable nanovesicles that are released by a wide range of cells and organs including the human placenta and fetal membranes. Interestingly, exosomes from placental origin have been uncovered in maternal circulation across gestation. In addition, their concentration is higher in pregnancies with complications such as gestational diabetes and preeclampsia. In normal gestation, the concentration of placental exosomes in maternal circulation correlates with placental weight at third trimester. The role of placental exosomes across gestation has not been fully elucidated, although recent studies suggest that placental exosomes are involved in maternal-fetal inmmuno-tolerance, maternal systemic inflammation and nutrient transport. The content of exosomes is of particular importance, encompassing a large range of molecules such as mRNA, miRNAs, DNA, lipids, cell-surface receptors, and protein mediators. These can in turn interact with either adjacent or distal cells to reprogram their phenotype and regulate their function. Many of the pro-parturition proinflammatory mediators reach maternal compartments from the fetal side via circulation, but major impediments remain, such as degradation at various levels and limited half-life in circulation. Recent findings suggest that a more effective mode of communication and signal transport is through exosomes, where signals are protected and will not succumb to degradation. Thus, understanding how exosomes regulate key events throughout pregnancy and parturition will provide an opportunity to understand the mechanisms involved in the maternal and fetal metabolic adaptations during normal and pathological pregnancies. Subsequently, this will assist in identifying those pregnancies at risk of developing complications. This may also allow more appropriate modifications of their clinical management. This review will hence examine the current body of data to summarise our understanding of how signaling pathways lead to the beginning of parturition. In addition, we propose that extracellular vesicles, namely exosomes, may be an integral component of these signaling events by transporting specific signals to prepare the maternal physiology to initiate parturition. Understanding these signals and their mechanisms in normal term pregnancies can provide insight into pathological activation of these signals, which can cause spontaneous preterm parturition. Hence, this review expands on our knowledge of exosomes as professional carriers of fetal signals to instigate human parturition.
AB - Parturition is defined as the action or process of giving birth to offspring. Normal term human parturition ensues following the maturation of fetal organ systems typically between 37 and 40 weeks of gestation. Our conventional understanding of how parturition initiation is signaled revolves around feto-maternal immune and endocrine changes occurring in the intrauterine cavity. These changes in turn correlate with the sequence of fetal growth and development. These important physiological changes also result in homeostatic imbalances which result in heightened inflammatory signaling. This disrupts the maintenance of pregnancy, thus leading to labor-related changes. However, the precise mechanisms of the signaling cascades that lead to the initiation of parturition remain unclear, although exosomes may be a mediator of this process. Exosomes are a subtype of extracellular vesicles characterised by their endocytic origin. This involves the trafficking of intraluminal vesicles into multivesicular bodies (MVB) and then exocytosis via the plasmatic membranes. Exosomes are highly stable nanovesicles that are released by a wide range of cells and organs including the human placenta and fetal membranes. Interestingly, exosomes from placental origin have been uncovered in maternal circulation across gestation. In addition, their concentration is higher in pregnancies with complications such as gestational diabetes and preeclampsia. In normal gestation, the concentration of placental exosomes in maternal circulation correlates with placental weight at third trimester. The role of placental exosomes across gestation has not been fully elucidated, although recent studies suggest that placental exosomes are involved in maternal-fetal inmmuno-tolerance, maternal systemic inflammation and nutrient transport. The content of exosomes is of particular importance, encompassing a large range of molecules such as mRNA, miRNAs, DNA, lipids, cell-surface receptors, and protein mediators. These can in turn interact with either adjacent or distal cells to reprogram their phenotype and regulate their function. Many of the pro-parturition proinflammatory mediators reach maternal compartments from the fetal side via circulation, but major impediments remain, such as degradation at various levels and limited half-life in circulation. Recent findings suggest that a more effective mode of communication and signal transport is through exosomes, where signals are protected and will not succumb to degradation. Thus, understanding how exosomes regulate key events throughout pregnancy and parturition will provide an opportunity to understand the mechanisms involved in the maternal and fetal metabolic adaptations during normal and pathological pregnancies. Subsequently, this will assist in identifying those pregnancies at risk of developing complications. This may also allow more appropriate modifications of their clinical management. This review will hence examine the current body of data to summarise our understanding of how signaling pathways lead to the beginning of parturition. In addition, we propose that extracellular vesicles, namely exosomes, may be an integral component of these signaling events by transporting specific signals to prepare the maternal physiology to initiate parturition. Understanding these signals and their mechanisms in normal term pregnancies can provide insight into pathological activation of these signals, which can cause spontaneous preterm parturition. Hence, this review expands on our knowledge of exosomes as professional carriers of fetal signals to instigate human parturition.
KW - Biomarkers
KW - Exosomes
KW - Gestation
KW - Parturition
KW - Placenta
KW - Preterm birth
UR - http://www.scopus.com/inward/record.url?scp=85048981053&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85048981053&partnerID=8YFLogxK
U2 - 10.2174/1381612824666180125164429
DO - 10.2174/1381612824666180125164429
M3 - Review article
C2 - 29376493
AN - SCOPUS:85048981053
SN - 1381-6128
VL - 24
SP - 974
EP - 982
JO - Current Pharmaceutical Design
JF - Current Pharmaceutical Design
IS - 9
ER -