Altered global gene expression in first trimester placentas of women destined to develop preeclampsia.
Altered global gene expression in first trimester placentas of women destined to develop preeclampsia.
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DOI：
10.1016/j.placenta.2008.09.015
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发表时间：
2009-01
期刊：
影响因子：
3.8
通讯作者：
Conrad, K. R.
中科院分区：
文献类型：
--
作者：
Founds, S. A.;Conley, Y. P.;Lyons-Weiler, J. F.;Jeyabalan, A.;Hogge, W. Allen;Conrad, K. R.
关键词：
先兆子痫是一种妊娠期特有疾病，仍然是孕产妇、胎儿和新生儿发病和死亡的主要原因，并且与未来心血管疾病的风险相关。除了分娩之外，没有可靠的预测因素、具体的预防措施或治疗方法。人们普遍认为，先兆子痫的前因是妊娠早期胎盘受损。因此，我们假设后来出现先兆子痫的妇女的妊娠早期胎盘中整体基因表达失调。在 160 名单胎胎儿的妊娠 10-12 周时收集了多余的绒毛膜绒毛取样 (CVS) 组织。 4 名患者出现先兆子痫，他们储存的 CVS 标本与来自未受影响妊娠患者的 8 份对照样本相匹配。 Affymetrix HG-U133 Plus 2.0 GeneChips 用于微阵列分析。进行了朴素贝叶斯预测模型和路径分析。 qRT-PCR 检查了三个失调基因。在先兆子痫胎盘中鉴定出 36 个差异表达基因。 qRT-PCR 验证了微阵列分析。三十一个基因被下调。许多与炎症/免疫调节和细胞运动有关。蜕膜基因失调很突出。没有发现缺氧和氧化应激调节基因改变的证据。据我们所知，这是第一项研究显示，在患先兆子痫之前约 6 个月，女性早期胎盘中基因表达失调，从而强化了该疾病的胎盘起源。我们假设先兆子痫的胎盘在妊娠前三个月因母体和胎儿免疫失调、异常蜕膜化或两者兼有而受到损害，从而损害滋养层侵袭。其中一些基因为孕早期母体血液中临床生物标志物的开发提供了潜在靶标。本文的补充材料可通过出版商的在线版本获得。
Preeclampsia is a pregnancy-specific disorder that remains a leading cause of maternal, fetal and neonatal morbidity and mortality, and is associated with risk for future cardiovascular disease. There are no reliable predictors, specific preventative measures or treatments other than delivery. A widely-held view is that the antecedents of preeclampsia lie with impaired placentation in early pregnancy. Accordingly, we hypothesized dysregulation of global gene expression in first trimester placentas of women who later manifested preeclampsia. Surplus chorionic villus sampling (CVS) tissues were collected at 10–12 weeks gestation in 160 patients with singleton fetuses. Four patients developed preeclampsia, and their banked CVS specimens were matched to 8 control samples from patients with unaffected pregnancies. Affymetrix HG-U133 Plus 2.0 GeneChips were utilized for microarray analysis. Naïve Bayes prediction modeling and pathway analysis were conducted. qRT-PCR examined three of the dysregulated genes. Thirty-six differentially expressed genes were identified in the preeclampsia placentas. qRT-PCR verified the microarray analysis. Thirty-one genes were down-regulated. Many were related to inflammation/immunoregulation and cell motility. Decidual gene dysregulation was prominent. No evidence was found for alterations in hypoxia and oxidative stress regulated genes. To our knowledge, this is the first study to show dysregulation of gene expression in the early placentas of women ~6 months before developing preeclampsia, thereby reinforcing a placental origin of the disorder. We hypothesize that placentation in preeclampsia is compromised in the first trimester by maternal and fetal immune dysregulation, abnormal decidualization, or both, thereby impairing trophoblast invasion. Several of the genes provide potential targets for the development of clinical biomarkers in maternal blood during the first trimester. Supplementary materials are available for this article via the publisher’s online edition.
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影响因子：
2
作者：
BISCHOF, P
通讯作者：
BISCHOF, P
影响因子：
6
作者：
Jauniaux, E;Watson, AL;Burton, GJ
通讯作者：
Burton, GJ
影响因子：
2.9
作者：
Ilekis, John V.;Reddy, Uma M.;Roberts, James M.
通讯作者：
Roberts, James M.
影响因子：
3.5
作者：
Jeschke, U;Kunert-Keil, C;Friese, K
通讯作者：
Friese, K
DOI：
10.1111/j.1471-0528.1986.tb07830.x
发表时间：
1986-10-01
期刊：
BRITISH JOURNAL OF OBSTETRICS AND GYNAECOLOGY
影响因子：
--
作者：
KHONG, TY;DEWOLF, F;BROSENS, I
通讯作者：
BROSENS, I