Placental expression profiling in preeclampsia: local overproduction of hemoglobin may drive pathological changes
Placental expression profiling in preeclampsia: local overproduction of hemoglobin may drive pathological changes
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DOI：
10.1016/j.fertnstert.2007.09.030
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发表时间：
2008-11-01
影响因子：
6.7
通讯作者：
Hansson, Stefan R.
中科院分区：
文献类型：
--
作者：
Centlow, Magnus;Carninci, Piero;Hansson, Stefan R.
目的：建立一个富含先兆子痫胎盘cDNA的文库，将其打印到微阵列上，用于先兆子痫（PE）和高危妊娠的胎盘获益。设定：大学妇女诊所和学术研究实验室。患者（S）：10例PE患者，5例PE和双侧切迹，5例双侧切迹无PE，15例正常血压患者。干预措施：分娩后收集胎盘和胎盘床活检。主要结果测量：产生PE转录物的亚克隆文库，并将来自这些文库的cDNA用于制备PE特异性cDNA阵列。结果进行了验证，定量使用实时聚合酶链反应（PCR）和组织学使用原位杂交和免疫组化。结果（S）：30个基因在至少一组比较显着改变。两个候选基因的差异使用定量实时PCR确认。血红蛋白α 2和γ转录显着过度表达的PE胎盘。胎盘和胎盘血管中的分散细胞被证明表达编码这些血红蛋白链的基因。结论：我们证明PE胎盘中血红蛋白的产生增加。血红蛋白可以释放到胎盘血管腔中。游离血红素和血红蛋白是引起内皮损伤和炎症的强效毒素。（Fertil Steril（（R））2008;90：1834-43. (c)2008年，美国生殖医学会（American Society for Reproductive Medicine）
Objective: To create a library enriched in cDNAs from preeclamptic placentas to print onto microarrays for placental profiting of preeclampsia (PE) and high risk pregnancies.Design: Prospective study. Setting: University women's clinic and academic research laboratory.Patient(S): Ten patients with PE, 5 with PE and bilateral notching, 5 with bilateral notching without PE, and 15 normotensive patients were recruited.Intervention(s): Placenta and placenta bed biopsies were collected after delivery.Main Outcome Measure(s): Subtracted libraries of PE transcripts were produced, and cDNAs from these libraries were used to make PE-specific cDNA arrays. Results were verified quantitatively using real-time polymerase chain reaction (PCR) and histologically using in situ hybridization and immunohistochemistry.Result(s): Thirty genes were significantly altered in at least one group comparison. Differences in two candidate genes were confirmed using quantitative real-time PCR. Hemoglobin alpha 2 and gamma transcripts were significantly over-expressed in the PE placenta. Scattered cells in the placenta and placental blood vessels were shown to express genes encoding these hemoglobin chains.Conclusion(s): We demonstrate increased hemoglobin production in the PE placenta. The hemoglobin may be released into the placenta blood vessel lumen. Free heme and hemoglobin are potent toxins that cause endothelial damage and inflammation. (Fertil Steril((R)) 2008;90:1834-43. (c) 2008 by American Society for Reproductive Medicine.)