Placenta-derived exosomes continuously increase in maternal circulation over the first trimester of pregnancy.
Placenta-derived exosomes continuously increase in maternal circulation over the first trimester of pregnancy.
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DOI：
10.1186/1479-5876-12-204
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发表时间：
2014-08-08
影响因子：
7.4
通讯作者：
Salomon C
中科院分区：
文献类型：
--
作者：
Sarker S;Scholz-Romero K;Perez A;Illanes SE;Mitchell MD;Rice GE;Salomon C
人胎盘在妊娠期间将特定的纳米囊泡（即外泌体）释放到母体循环中，然而，在妊娠早期母体血液中胎盘来源的外泌体的存在仍有待确定。本研究的目的是确定妊娠早期（即6至12周）期间正常妊娠妇女血浆中胎盘来源的外泌体浓度的孕龄相关变化。时间序列实验设计用于建立妊娠前三个月期间母体血浆外泌体浓度的妊娠相关变化。在妊娠6、7、8、9、10、11和12周时从正常健康女性（10名患者）收集一系列血浆（n = 70）。我们通过定量和观察这些囊泡在冻融过程后的蛋白质和miRNA含量来测量它们的稳定性。通过使用蔗糖连续梯度的差速和浮力密度离心分离外来体，并分别使用纳米颗粒跟踪分析（NTA; Nanosight™）和电子显微镜（EM）通过它们的尺寸分布和形态表征外来体。通过定量免疫反应性外泌体标志物CD 63和胎盘特异性标志物（胎盘碱性磷酸酶PLAP）来确定外泌体和胎盘来源的外泌体的总数。这些纳米粒子非常稳定。有没有显着下降，其产量与冻/融过程或改变其EM形态。NTA早在妊娠6周时就发现母体血浆中存在50-150 nm的球形囊泡。母体循环中外来体的数量随着妊娠的进展（从6至12周）显著增加（ANOVA，p = 0.002）。母体血浆中胎盘来源的外泌体的浓度（即PLAP+）随着胎龄逐渐增加，从6周70.6 ± 5.7 pg/ml增加至12周117.5 ± 13.4 pg/ml。回归分析显示，周数是解释血浆外泌体PLAP浓度中>70%的观察到的变化的因素，而总外泌体数量仅解释20%。在正常的健康妊娠期间，母体血浆中存在的外泌体数量在妊娠的前三个月随胎龄显著增加。这项研究是一个基线，为开发早期检测方法提供了一个理想的起点，用于随后发生妊娠并发症的女性，在妊娠中期临床检测到。早期发现有妊娠并发症风险的妇女将提供一个机会，以制定和评估适当的干预策略，以限制急性不良后果。
Human placenta releases specific nanovesicles (i.e. exosomes) into the maternal circulation during pregnancy, however, the presence of placenta-derived exosomes in maternal blood during early pregnancy remains to be established. The aim of this study was to characterise gestational age related changes in the concentration of placenta-derived exosomes during the first trimester of pregnancy (i.e. from 6 to 12 weeks) in plasma from women with normal pregnancies. A time-series experimental design was used to establish pregnancy-associated changes in maternal plasma exosome concentrations during the first trimester. A series of plasma were collected from normal healthy women (10 patients) at 6, 7, 8, 9, 10, 11 and 12 weeks of gestation (n = 70). We measured the stability of these vesicles by quantifying and observing their protein and miRNA contents after the freeze/thawing processes. Exosomes were isolated by differential and buoyant density centrifugation using a sucrose continuous gradient and characterised by their size distribution and morphology using the nanoparticles tracking analysis (NTA; Nanosight™) and electron microscopy (EM), respectively. The total number of exosomes and placenta-derived exosomes were determined by quantifying the immunoreactive exosomal marker, CD63 and a placenta-specific marker (Placental Alkaline Phosphatase PLAP). These nanoparticles are extraordinarily stable. There is no significant decline in their yield with the freeze/thawing processes or change in their EM morphology. NTA identified the presence of 50–150 nm spherical vesicles in maternal plasma as early as 6 weeks of pregnancy. The number of exosomes in maternal circulation increased significantly (ANOVA, p = 0.002) with the progression of pregnancy (from 6 to 12 weeks). The concentration of placenta-derived exosomes in maternal plasma (i.e. PLAP+) increased progressively with gestational age, from 6 weeks 70.6 ± 5.7 pg/ml to 12 weeks 117.5 ± 13.4 pg/ml. Regression analysis showed that weeks is a factor that explains for >70% of the observed variation in plasma exosomal PLAP concentration while the total exosome number only explains 20%. During normal healthy pregnancy, the number of exosomes present in the maternal plasma increased significantly with gestational age across the first trimester of pregnancy. This study is a baseline that provides an ideal starting point for developing early detection method for women who subsequently develop pregnancy complications, clinically detected during the second trimester. Early detection of women at risk of pregnancy complications would provide an opportunity to develop and evaluate appropriate intervention strategies to limit acute adverse sequel.
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影响因子：
5.8
作者：
Pant S;Hilton H;Burczynski ME
通讯作者：
Burczynski ME
联邦交易体：真正提供的工程治疗生物纳米颗粒。
DOI：
10.3390/ph6050659
发表时间：
2013
期刊：
Pharmaceuticals (Basel, Switzerland)
影响因子：
--
作者：
Marcus ME;Leonard JN
通讯作者：
Leonard JN
影响因子：
2.6
作者：
Bashiri, Asher;Katz, Ohad;Mazor, Moshe
通讯作者：
Mazor, Moshe
DOI：
10.1073/pnas.1304718110
发表时间：
2013-07-16
影响因子：
11.1
作者：
Delorme-Axford, Elizabeth;Donker, Rogier B.;Coyne, Carolyn B.
通讯作者：
Coyne, Carolyn B.
影响因子：
3.4
作者：
Kalra, Hina;Adda, Christopher G.;Mathivanan, Suresh
通讯作者：
Mathivanan, Suresh