Sitras V, Paulssen R H, Grønaas H, Leirvik J, Hanssen T A, Vårtun A, Acharya G
Department of Obstetrics and Gynecology, University Hospital of Northern Norway, University of Tromsø, Tromsø, Norway.
Placenta. 2009 May;30(5):424-33. doi: 10.1016/j.placenta.2009.01.012. Epub 2009 Feb 26.
We investigated the global placental gene expression profile in severe preeclampsia. Twenty-one women were randomly selected from 50 participants with uncomplicated pregnancies to match 21 patients with severe preeclampsia. A 30K Human Genome Survey Microarray v.2.0 (Applied Biosystems) was used to evaluate the gene expression profile. After RNA isolation, five preeclamptic placentas were excluded due to poor RNA quality. The series composed of 37 hybridizations in a one-channel detection system of chemiluminescence emitted by the microarrays. An empirical Bayes analysis was applied to find differentially expressed genes. In preeclamptic placentas 213 genes were significantly (fold-change>or=2 and p<or=0.01) up-regulated and 82 were down-regulated, compared with normal placentas. Leptin (40 fold), laeverin (10 fold), different isoforms of beta-hCG (3-6 fold), endoglin (4 fold), FLT1 (3 fold) and FLT4 (2 fold) were up-regulated. PDGFD was down-regulated (2 fold). Several differentially expressed genes were associated with Alzheimer disease, angiogenesis, Notch-, TGFbeta- and VEGF-signalling pathways. Sixteen genes best discriminated preeclamptic from normal placentas. Comparison between early- (<34 weeks) and late-onset preeclampsia showed 168 differentially expressed genes with oxidative stress, inflammation, and endothelin signalling pathways mainly involved in early-onset disease. Validation of the microarray results was performed by RT-PCR, quantitative urine hCG measurement and placental histopathologic examination. In summary, placental gene expression is altered in preeclampsia and we provide a comprehensive list of the differentially expressed genes. Placental gene expression is different between early- and late-onset preeclampsia, suggesting differences in pathophysiology.
我们研究了重度子痫前期患者胎盘的整体基因表达谱。从50例无并发症妊娠的参与者中随机选取21名女性，与21例重度子痫前期患者进行匹配。使用30K人类基因组调查微阵列v.2.0（应用生物系统公司）评估基因表达谱。RNA分离后，由于RNA质量差，排除了5个子痫前期胎盘。该系列由微阵列发出的化学发光单通道检测系统中的37次杂交组成。应用经验贝叶斯分析来寻找差异表达基因。与正常胎盘相比，子痫前期胎盘中213个基因显著上调（倍数变化≥2且p≤0.01），82个基因下调。瘦素（40倍）、拉维林（10倍）、β - hCG的不同异构体（3 - 6倍）、内皮糖蛋白（4倍）、FLT1（3倍）和FLT4（2倍）上调。血小板衍生生长因子D（PDGFD）下调（2倍）。几个差异表达基因与阿尔茨海默病、血管生成、Notch、TGFβ和VEGF信号通路相关。16个基因最能区分子痫前期胎盘与正常胎盘。早发型（<34周）和晚发型子痫前期的比较显示有168个差异表达基因，氧化应激、炎症和内皮素信号通路主要参与早发型疾病。通过逆转录聚合酶链反应（RT-PCR）、定量尿hCG测量和胎盘组织病理学检查对微阵列结果进行验证。总之，子痫前期患者胎盘基因表达发生改变，我们提供了差异表达基因的综合列表。早发型和晚发型子痫前期的胎盘基因表达不同，提示病理生理学存在差异。
