Molecular evidence of placental hypoxia in preeclampsia
Molecular evidence of placental hypoxia in preeclampsia
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DOI：
10.1210/jc.2005-0078
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发表时间：
2005-07-01
影响因子：
5.8
通讯作者：
Caniggia, I
中科院分区：
文献类型：
--
作者：
Soleymanlou, N;Jurisica, I;Caniggia, I
背景：氧气在包括先兆子痫的人类胎盘病理中起着核心作用，这是胎儿和孕产妇死亡和发病率的主要原因。据信，前启示识中的子宫牙科氧合不足是导致这种疾病的临床表现的分子事件。Design：使用高通量功能基因组学，我们确定了来自高海拔妊娠的全球基因表达特征慢性缺氧的模型以及3％和20％氧气（一种体外器官培养模型）下的第一孕期外植体的模型。接下来，我们比较了这两个模型的基因组谱与先兆子痫复杂的妊娠获得的基因组谱。使用二进制树结构矢量量化算法分析了微阵列数据，该算法生成全局基因表达图。结果：我们的结果突出了3％O-2处理的epplants，高蓝色placentae和重要的胎盘之间的惊人全局基因表达相似性来自先兆子痫的怀孕。我们在此证明了外植体培养物和高海拔胎盘的实用性，作为研究前宾夕法尼亚中氧介导的事件的生物学相关和有力的模型。结论：我们的结果提供了分子证据，表明可能会减少先兆子痫的异常胎盘基因表达变化。氧合和这些事件可以通过体内和体外胎盘缺氧模型成功地模仿。
Background: Oxygen plays a central role in human placental pathologies including preeclampsia, a leading cause of fetal and maternal death and morbidity. Insufficient uteroplacental oxygenation in preeclampsia is believed to be responsible for the molecular events leading to the clinical manifestations of this disease.Design: Using high-throughput functional genomics, we determined the global gene expression profiles of placentae from high altitude pregnancies, a natural in vivo model of chronic hypoxia, as well as that of first-trimester explants under 3 and 20% oxygen, an in vitro organ culture model. We next compared the genomic profile from these two models with that obtained from pregnancies complicated by preeclampsia. Microarray data were analyzed using the binary tree-structured vector quantization algorithm, which generates global gene expression maps.Results: Our results highlight a striking global gene expression similarity between 3% O-2-treated explants, high-altitude placentae, and importantly placentae from preeclamptic pregnancies. We demonstrate herein the utility of explant culture and high-altitude placenta as biologically relevant and powerful models for studying the oxygen-mediated events in preeclampsia.Conclusion: Our results provide molecular evidence that aberrant global placental gene expression changes in preeclampsia may be due to reduced oxygenation and that these events can successfully be mimicked by in vivo and in vitro models of placental hypoxia.