Programmed Fetal Membrane Senescence and Exosome-Mediated Signaling: A Mechanism Associated With Timing of Human Parturition.
Programmed Fetal Membrane Senescence and Exosome-Mediated Signaling: A Mechanism Associated With Timing of Human Parturition.
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DOI：
10.3389/fendo.2017.00196
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发表时间：
2017
影响因子：
5.2
通讯作者：
Taylor RN
中科院分区：
文献类型：
--
作者：
Menon R;Mesiano S;Taylor RN
人类分娩是一个炎症过程，涉及胎儿和母亲的房室。在分娩过程中，人类子宫组织中免疫细胞的精确相互作用尚未得到很好的描述，但对人类分娩起始的见解已经通过动物模型的研究得到了证实。不幸的是，胎生物种之间相对于胎儿成熟的分娩时间是不同的——这表明不同的系统发育时钟和警报——但很清楚的是，重要的共同途径必须汇聚在一起来控制分娩过程。在此，我们假设了一种由人类胎膜老化和衰老相关炎症引发的新的信号机制。胎膜老化的程序性事件与胎儿生长和器官成熟相一致。从机制上讲，衰老涉及端粒缩短和p38丝裂原激活的信号激酶的激活，导致衰老相关的表型转变。衰老组织释放炎症信号，通过外泌体传播，引起母体子宫组织功能改变。在体外，氧化应激导致炎症介质（衰老相关的分泌表型和损伤相关的分子模式标记物）的释放增加，这些炎症介质可以被包装在外泌体中。这些外泌体穿过组织层，到达母体组织，增加总体炎症负荷，使它们从静止状态转变为活跃状态。动物模型研究表明，胎儿外泌体可以从胎儿转移到母体。因此，老化的胎膜和膜源性外泌体将胎儿信号运送到子宫和子宫颈，并可能引发分娩。本文综述了基于正在进行的人类胎膜模型系统研究数据的人类分娩研究中的一个新假设。
Human parturition is an inflammatory process that involves both fetal and maternal compartments. The precise immune cell interactions have not been well delineated in human uterine tissues during parturition, but insights into human labor initiation have been informed by studies in animal models. Unfortunately, the timing of parturition relative to fetal maturation varies among viviparous species—indicative of different phylogenetic clocks and alarms—but what is clear is that important common pathways must converge to control the birth process. Herein, we hypothesize a novel signaling mechanism initiated by human fetal membrane aging and senescence-associated inflammation. Programmed events of fetal membrane aging coincide with fetal growth and organ maturation. Mechanistically, senescence involves in telomere shortening and activation of p38 mitogen-activated signaling kinase resulting in aging-associated phenotypic transition. Senescent tissues release inflammatory signals that are propagated via exosomes to cause functional changes in maternal uterine tissues. In vitro, oxidative stress causes increased release of inflammatory mediators (senescence-associated secretory phenotype and damage-associated molecular pattern markers) that can be packaged inside the exosomes. These exosomes traverse through tissues layers, reach maternal tissues to increase overall inflammatory load transitioning them from a quiescent to active state. Animal model studies have shown that fetal exosomes can travel from fetal to the maternal side. Thus, aging fetal membranes and membrane-derived exosomes cargo fetal signals to the uterus and cervix and may trigger parturition. This review highlights a novel hypothesis in human parturition research based on data from ongoing research using human fetal membrane model system.
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DOI：
10.1111/aji.12274
发表时间：
2014-10
期刊：
American journal of reproductive immunology (New York, N.Y. : 1989)
影响因子：
--
作者：
Girard S;Heazell AE;Derricott H;Allan SM;Sibley CP;Abrahams VM;Jones RL
通讯作者：
Jones RL
DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Coppé JP;Desprez PY;Krtolica A;Campisi J
通讯作者：
Campisi J
影响因子：
9.8
作者：
Behnia, Faranak;Taylor, Brandie D.;Menon, Ramkumar
通讯作者：
Menon, Ramkumar
影响因子：
3.5
作者：
De Felice, Bruna;Nappi, Carmine;Guida, Maurizio
通讯作者：
Guida, Maurizio
DOI：
10.1016/0002-9378(87)90070-6
发表时间：
1987-03-01
影响因子：
9.8
作者：
BENNETT, PR;ROSE, MP;ELDER, MG
通讯作者：
ELDER, MG