PDF(Pubmed)
Abstract：
UNASSIGNED: The relationship between placental pathology and the maternal syndrome of preeclampsia is incompletely characterized. Mismatch between placental nutrient supply and fetal demands induces stress in the syncytiotrophoblast, the layer of placenta in direct contact with maternal blood. Such stress alters the content and increases the release of syncytiotrophoblast extracellular vesicles (STB-EVs) into the maternal circulation. We have previously shown 5\'-tRNA fragments (5\'-tRFs) constitute the majority of small RNA in STB-EVs in healthy pregnancy. 5\'-tRFs are produced in response to stress. We hypothesized STB-EV 5\'-tRF release might change in preeclampsia.
UNASSIGNED: We perfused placentas from 8 women with early-onset preeclampsia and 6 controls, comparing small RNA expression in STB-EVs. We used membrane-affinity columns to isolate maternal plasma vesicles and investigate placental 5\'-tRFs in vivo. We quantified 5\'-tRFs from circulating STB-EVs using a placental alkaline phosphatase immunoassay. 5\'-tRFs and scrambled RNA controls were added to monocyte, macrophage and endothelial cells in culture to investigate transcriptional responses.
UNASSIGNED: 5\'-tRFs constitute the majority of small RNA in STB-EVs from both preeclampsia and normal pregnancies. More than 900 small RNA fragments are differentially expressed in preeclampsia STB-EVs. Preeclampsia-dysregulated 5\'-tRFs are detectable in maternal plasma, where we identified a placentally derived load. 5\'-tRF-Glu-CTC, the most abundant preeclampsia-upregulated 5\'-tRF in perfusion STB-EVs, is also increased in preeclampsia STB-EVs from maternal plasma. 5\'-tRF-Glu-CTC induced inflammation in macrophages but not monocytes. The conditioned media from 5\'-tRF-Glu-CTC-activated macrophages reduced eNOS (endothelial NO synthase) expression in endothelial cells.
UNASSIGNED: Increased release of syncytiotrophoblast-derived vesicle-bound 5\'-tRF-Glu-CTC contributes to preeclampsia pathophysiology.
UNASSIGNED: We perfused placentas from 8 women with early-onset preeclampsia and 6 controls, comparing small RNA expression in STB-EVs. We used membrane-affinity columns to isolate maternal plasma vesicles and investigate placental 5\'-tRFs in vivo. We quantified 5\'-tRFs from circulating STB-EVs using a placental alkaline phosphatase immunoassay. 5\'-tRFs and scrambled RNA controls were added to monocyte, macrophage and endothelial cells in culture to investigate transcriptional responses.
UNASSIGNED: 5\'-tRFs constitute the majority of small RNA in STB-EVs from both preeclampsia and normal pregnancies. More than 900 small RNA fragments are differentially expressed in preeclampsia STB-EVs. Preeclampsia-dysregulated 5\'-tRFs are detectable in maternal plasma, where we identified a placentally derived load. 5\'-tRF-Glu-CTC, the most abundant preeclampsia-upregulated 5\'-tRF in perfusion STB-EVs, is also increased in preeclampsia STB-EVs from maternal plasma. 5\'-tRF-Glu-CTC induced inflammation in macrophages but not monocytes. The conditioned media from 5\'-tRF-Glu-CTC-activated macrophages reduced eNOS (endothelial NO synthase) expression in endothelial cells.
UNASSIGNED: Increased release of syncytiotrophoblast-derived vesicle-bound 5\'-tRF-Glu-CTC contributes to preeclampsia pathophysiology.
摘要：
■胎盘病理与先兆子痫的母体综合征之间的关系未完全表征。胎盘营养供应和胎儿需求之间的不匹配引起合胞体滋养层的应激，胎盘层与母体血液直接接触。这种压力改变了内容并增加了合胞体滋养层细胞外囊泡（STB-EV）向母体循环的释放。我们先前已经显示5'-tRNA片段(5'-tRF)构成健康妊娠中STB-EV中的大部分小RNA。5'-tRF是响应压力而产生的。我们假设STB-EV5'-tRF释放可能在先兆子痫中发生变化。
■我们灌注了8例早发型先兆子痫妇女和6例对照者的胎盘，比较STB-EV中的小RNA表达。我们使用膜亲和柱分离母体血浆囊泡，并在体内研究胎盘5'-tRF。我们使用胎盘碱性磷酸酶免疫测定法对循环STB-EV的5'-tRF进行了定量。将5'-tRF和乱序RNA对照添加到单核细胞中，培养中的巨噬细胞和内皮细胞研究转录反应。
■5'-tRFs构成了来自先兆子痫和正常妊娠的STB-EV中的大部分小RNA。900多个小RNA片段在先兆子痫STB-EV中差异表达。孕妇血浆中可检测到子痫前期失调的5'-tRF，在那里我们确定了一个胎盘衍生的负荷。5\'-tRF-Glu-CTC,灌注STB-EV中最丰富的先兆子痫上调5'-tRF，来自母体血浆的先兆子痫STB-EV也增加。5'-tRF-Glu-CTC在巨噬细胞而不是单核细胞中诱导炎症。来自5'-tRF-Glu-CTC激活的巨噬细胞的条件培养基降低了内皮细胞中eNOS(内皮NO合酶)的表达。
■合胞体滋养层来源的囊泡结合5'-tRF-Glu-CTC的释放增加有助于先兆子痫的病理生理学。
■我们灌注了8例早发型先兆子痫妇女和6例对照者的胎盘，比较STB-EV中的小RNA表达。我们使用膜亲和柱分离母体血浆囊泡，并在体内研究胎盘5'-tRF。我们使用胎盘碱性磷酸酶免疫测定法对循环STB-EV的5'-tRF进行了定量。将5'-tRF和乱序RNA对照添加到单核细胞中，培养中的巨噬细胞和内皮细胞研究转录反应。
■5'-tRFs构成了来自先兆子痫和正常妊娠的STB-EV中的大部分小RNA。900多个小RNA片段在先兆子痫STB-EV中差异表达。孕妇血浆中可检测到子痫前期失调的5'-tRF，在那里我们确定了一个胎盘衍生的负荷。5\'-tRF-Glu-CTC,灌注STB-EV中最丰富的先兆子痫上调5'-tRF，来自母体血浆的先兆子痫STB-EV也增加。5'-tRF-Glu-CTC在巨噬细胞而不是单核细胞中诱导炎症。来自5'-tRF-Glu-CTC激活的巨噬细胞的条件培养基降低了内皮细胞中eNOS(内皮NO合酶)的表达。
■合胞体滋养层来源的囊泡结合5'-tRF-Glu-CTC的释放增加有助于先兆子痫的病理生理学。
