Placental hypoxia during placental malaria
Placental hypoxia during placental malaria
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DOI：
10.1086/526521
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发表时间：
2008-03-01
影响因子：
6.4
通讯作者：
Rogerson, Stephen J.
中科院分区：
文献类型：
--
作者：
Boeuf, Philippe;Tan, Aimee;Rogerson, Stephen J.
背景。胎盘疟疾引起胎儿生长迟缓（FGR），这在流行病学上与胎盘单核细胞浸润有关。我们研究了疟原虫或单核细胞浸润是否与胎盘缺氧有关，作为疟疾fgr的潜在机制。我们研究了缺氧标志物缺氧诱导因子(HIF)-1 α、血管内皮生长因子（VEGF）、胎盘生长因子、VEGF受体1及其可溶性形态、VEGF受体2。我们使用实时聚合酶链反应（59名女性）来检测基因转录，免疫组织化学（30名女性）来描述蛋白质表达，激光捕获显微解剖（23名女性）来检测基因表达的特异性变化。我们比较了基因和蛋白表达与疟疾感染、单核细胞浸润和出生体重的关系。我们不能将胎盘疟疾的任何标志与缺氧反应的转录、表达或组织分布特征联系起来，但我们发现疟疾病例的合细胞滋养细胞中HIF-1 α水平（P = 0.0005）和VEGF水平（P = 0.0026）高于无症状对照胎盘。我们的数据与胎盘缺氧在疟疾相关FGR发病机制中的作用不一致。激光捕获显微解剖研究规模较小，但其结果表明：(1)疟疾影响合体滋养细胞基因转录；(2)胎盘疟疾相关FGR的新潜在机制。
Background. Placental malaria causes fetal growth retardation (FGR), which has been linked epidemiologically to placental monocyte infiltrates. We investigated whether parasite or monocyte infiltrates were associated with placental hypoxia, as a potential mechanism underlying malarial FGR.Methods. We studied the hypoxia markers hypoxia inducible factor (HIF)-1 alpha, vascular endothelial growth factor (VEGF), placental growth factor, VEGF receptor 1 and its soluble form, and VEGF receptor 2. We used real-time polymerase chain reaction (in 59 women) to examine gene transcription, immunohistochemistry (in 30 women) to describe protein expression, and laser-capture microdissection (in 23 women) to examine syncytiotrophoblast-specific changes in gene expression. We compared gene and protein expression in relation to malaria infection, monocyte infiltrates, and birth weight.Results. We could not associate any hallmark of placental malaria with a transcription, expression, or tissue-distribution profile characteristic of a response to hypoxia, but we found higher HIF-1 alpha levels (P = .0005) and lower VEGF levels (P = .0026) in the syncytiotrophoblasts of cases of malaria than in those of asymptomatic control placentas.Conclusions. Our data are inconsistent with a role for placental hypoxia in the pathogenesis of malaria-associated FGR. The laser-capture microdissection study was small, but its results suggest (1) that malaria affects syncytiotrophoblast-gene transcription and (2) novel potential mechanisms for placental malaria-associated FGR.