Placental Exosomes During Gestation: Liquid Biopsies Carrying Signals for the Regulation of Human Parturition.
Placental Exosomes During Gestation: Liquid Biopsies Carrying Signals for the Regulation of Human Parturition.
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DOI：
10.2174/1381612824666180125164429
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发表时间：
2018
影响因子：
3.1
通讯作者：
C. Salomon;Zarin Nuzhat;C. Dixon;R. Menon
中科院分区：
文献类型：
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作者：
C. Salomon;Zarin Nuzhat;C. Dixon;R. Menon
分娩被定义为生育后代的行为或过程。正常足月的人类分娩是在胎儿器官系统成熟后进行的，通常是在妊娠37到40周之间。我们对分娩开始如何发出信号的传统理解是围绕着宫腔内发生的母胎免疫和内分泌变化。这些变化反过来又与胎儿生长发育的顺序相关。这些重要的生理变化也会导致体内平衡失衡，从而导致炎症信号的增强。这会扰乱妊娠的维持，从而导致与分娩相关的变化。然而，导致分娩启动的信号级联反应的确切机制仍不清楚，尽管外切体可能是这一过程的中介。胞外体是胞外囊泡的一种亚型，其特点是来源于内吞。这涉及到腔内小泡进入多囊泡体(MVB)，然后通过质膜进行胞吐作用。Exosome是一种高度稳定的纳米囊泡，可由多种细胞和器官释放，包括人类胎盘和胎膜。有趣的是，在孕期母体循环中发现了胎盘来源的外周血糖体。此外，在妊娠期糖尿病和先兆子痫等并发症的孕妇中，它们的浓度更高。在正常妊娠中，母体循环中胎盘外体的浓度与妊娠晚期的胎盘重量相关。胎盘外切体在妊娠过程中的作用尚未完全阐明，尽管最近的研究表明胎盘外切体参与母婴免疫耐受、母体全身炎症和营养物质运输。外切体的含量尤其重要，它包含了大量的分子，如信使核糖核酸、微核糖核酸、DNA、脂质、细胞表面受体和蛋白质介体。这些细胞可以反过来与相邻或远端细胞相互作用，重新编程它们的表型，并调节它们的功能。许多助产促炎介质通过循环从胎儿一侧到达母体间隔，但主要障碍仍然存在，如不同水平的降解和有限的循环半衰期。最近的发现表明，一种更有效的通信和信号传输模式是通过外体，信号受到保护，不会屈服于退化。因此，了解外切体如何调节整个妊娠和分娩过程中的关键事件，将为理解正常和病理怀孕期间母婴代谢适应所涉及的机制提供机会。随后，这将有助于确定那些有发生并发症风险的妊娠。这也可能允许对他们的临床管理进行更适当的修改。因此，这篇综述将研究目前的数据，以总结我们对信号通路如何导致分娩开始的理解。此外，我们认为，胞外小泡，即外体，可能是这些信号事件的一个组成部分，通过运输特定的信号来为母体生理开始分娩做准备。了解这些信号及其在正常足月妊娠中的机制，可以深入了解这些信号的病理激活，这可能导致自发的早产。因此，这篇综述扩展了我们对外切体作为胎儿信号专业携带者的知识，从而促使人类分娩。
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 laborrelated 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 halflife 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.