Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of placenta from women who underwent a normal pregnancy and from those suffering from early or late onset pre-eclampsia

ABSTRACT: Pre-eclampsia is one of the most serious pregnancy-associated disorders, and is defined by hypertension (systolic blood pressure higher than 140mmHg or diastolic blood pressure higher than 90mmHg) with proteinuria (more than 0.3g/day). It is not a simple complication of pregnancy, but is rather a syndrome of multiple organ failure involving the liver, kidney, and lung, as well as coagulatory and neural systems. There is now an emerging consensus that pre-eclampsia is a complex polygenetic trait in which maternal and fetal genes, as well as environmental factors, are involved, although the precise mechanism of the disorder has remained elusive. In this study, we have performed gene expression profiling to further elucidate the mechanisms underlying the development of the pre-eclamptic condition. We thus compared the expression profiles in placentas from women who underwent a normal pregnancy and from women suffering from severe pre-eclampsia. In addition, we compared the expression data between the early and late onset forms of pre-eclampsia and obtained a number of potential new prognostic biomarkers for this disease. Experiment Overall Design: Placental biopsies were obtained during Caesarean section from both normotensive patients and from those with pre-eclampsia (n = 14) (early onset type; earlier than 31 weeks gestation, n = 6 and late onset type; 31 weeks gestation or later, n = 8). Pre-eclampsia was defined as a blood pressure of higher than 160/110 mmHg, with proteinuria of more than 2g in a 24 hour collection. The expression profiles of approximately 47,669 genes were analyzed using a Whole Human Genome Oligo Microarray Kit (Agilent Technologies). A total of 10 placentas from women with pre-eclampsia and four from normal subjects were used in the hybridizations. Reverse transcription labeling and hybridization was performed using the protocol recommended by the manufacturer. The microarray experiments were then carried out using competitive hybridization experiments with Cy3 and Cy5-labeled targets; one with test placental RNAs from patients or normal control subjects, and another using pooled normal placental RNA as a template control for normalization. The glass slides were scanned using an Agilent G2565BA microarray scanner. Scanned images were then analyzed using Feature Extraction software. The average signal intensities were corrected for median background intensity and transferred with GenBank descriptors to a Microsoft Excel data spreadsheet (Microsoft, Redmond, WA). Data analysis was performed using Genespring software version 6.1 (Silicon Genetics, Redwood City, CA). After intensity dependent normalization (Lowess), the expression levels relative to the control were calculated as a ratio, and the expression profiles were then compared between each pre-eclamptic or normal sample.

ORGANISM(S): Homo sapiens

DISEASE(S): early onset preeclampsia

SUBMITTER: Haruki Nishizawa

PROVIDER: E-GEOD-4707 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Microarray analysis of differentially expressed fetal genes in placental tissue derived from early and late onset severe pre-eclampsia.

Nishizawa H H Pryor-Koishi K K Kato T T Kowa H H Kurahashi H H Udagawa Y Y

Placenta 20060724 5-6

Although it has been well documented that pre-eclampsia is caused by a combination of maternal and fetal susceptibility genes, little is known about the precise etiology of this complicated disorder. To investigate how the expression of fetal genes contributes to the mechanisms underlying the progression of this disease, we have analyzed differentially expressed genes using placentas from 13 normal pregnancies and 14 pregnancies with severe pre-eclampsia. We performed genome-wide expression prof ...[more]

PMID: 16860862

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Project description:Background: Preeclampsia (PE) is a placental disease characterized by hypertension and proteinuria in pregnant women, which is associated with a high maternal and infantile morbidity. However, circulating biomarkers able to predict the prognosis of PE are lacking. Methods: Thirty-eight women were included in the study. They consisted of 19 patients with PE (13 with severe PE and 6 women with non-severe PE) and 19 gestational age-matched normal pregnancy controls. We measured coagulation pathway, endothelial responses and microparticle release and circulating gene expression in PE patient groups and normotensive controls. Results: The measurement of markers associated with coagulation pathway, endothelial activation and circulating microparticles enabled to discriminate PE from normal pregnancy but were not sufficient to distinguish severe from non-severe PE. PE patients also exhibited a specific transcriptional program distinct from that of control women and subtle differences were observed between severe and non-severe PE. Functional annotation of the up-modulated signature in PE highlighted two main functions related to ribosome and complement. Importantly, we found that 8 genes were specifically up-modulated in severe preeclampsia. Among these genes, the expression of VSIG4 was significantly increased in patients with severe preeclampsia in comparison with controls and patients with non-severe preeclampsia. Conclusion: Using transcriptional signatures of blood samples, we identified the gene encoding the estrogen receptor as a potential diagnostic marker of severe preeclampsia. In addition, the determination of this gene may improve the prognostic assessment of severe preeclampsia. Thirty-eight women were included in the study: 19 patients with PE, including 6 women with non-severe PE and 13 with severe PE, and 19 women with normal pregnancy (NP) selected according to age, weight, smoking status, race, gestational age at the inclusion, and blood pH (Table 1 of manuscript). Women with NP had no history of medical illness or medication, and received routing prenatal care. The diagnostic of PE was based on a blood pressure of M-bM-^IM-% 140/90 mmHg taken twice, uricemia above normal laboratory range (120-420 M-BM-5mol/L), and proteinuria higher than 300 mg in a 24 hour-collection, occurring after 20 gestational weeks in previously normotensive women (Table 2). The criteria used to define severe PE included one of the following conditions: a blood pressure higher than 160/110 mmHg, a proteinuria higher than 1500 mg/24h), a multisystem disorder, maternal cerebral symptoms (seizures, stroke) or intrauterine growth restriction below the 3M-BM-0 percentile. Women with multiple gestations, fetal congenital malformations/chromosomal abnormalities, recent infection, antiphospholipid antibodies, trauma, drug or alcohol abuse during pregnancy, preexisting hypertension, thrombophilia with PE history, or women receiving anticoagulant or antiaggregation therapy were excluded from the study. Two microarrays (one non-severe PE and one normal) were discarded from the analysis for technical reasons. Thus, only 36 microarrays are included here.

Project description:Hypertension in pregnancy is the leading cause of morbidity and mortality in pregnancy, affecting up to 10% of all gestations1. Hypertensive disorders of pregnancy include chronic hypertension, gestational hypertension, eclampsia and pre-eclampsia, all of which increase the risk of complications in both mothers and babies during gestation. Preeclampsia, in particular, is characterised by the new-onset of gestational hypertension in the presence of proteinuria or other organ damage. It affects 5-7% of pregnancies and causes approximately 76,000 maternal deaths and 500,000 foetal deaths worldwide each year2. The classification of preeclampsia has been evolving over the last decade. In 2013, American College of Obstetricians and Gynecologists (ACOG) and International Society for the Study of Hypertension in Pregnancy (ISSHP) in the absence of proteinuria included other symptoms/features including liver dysfunction, thrombocytopenia, cerebrovascular events or foetal growth restriction (FGR) in the diagnosis of preeclampsia 1,3,4. Despite the fact that preeclampsia is a multifactorial and heterogeneous disorder, it is now widely accepted that preeclampsia is stratified depending on the time of onset into: i) early-onset PE (EOPE) manifested before 34 weeks of gestation, and ii) late-onset PE (LOPE) manifested from 34 weeks of gestation. Although EOPE and LOPE share the same diagnostic criteria, these two phenotypes of preeclampsia lead to different outcomes. EOPE is commonly associated with FGR, abnormal uterine artery Doppler often leading to preterm birth and higher risk of post-pregnancy morbidities5,6. On the other hand, LOPE appears to be a less severe disorder, often with normal or slightly increased uterine resistance index and a low rate of FGR6,7. Distinct delineation between EOPE and LOPE is still not well understood, with most patients with preeclampsia presenting elements of both pathologies proposing a clinical spectrum for preeclampsia. The lack of untargeted discovery studies involving ‘omics’ analyses has impeded understanding of the molecular differences between these two phenotypes of preeclampsia. Notably, a study from 20058 utilised a proteomics approach using urine samples from a cohort of pregnant women with EOPE and healthy controls, however the differences between EOPE and LOPE were not elucidated. Another more recent bioinformatics study, identified overlapping pathogenic mechanisms between preeclampsia, hypertension and heart disease but could not stratify between EOPE and LOPE due to underreported of data related to individual phenotypes9. In this study, we conducted an unbiased, comprehensive proteomics investigation using plasma samples collected from patients with EOPE (n=17) and LOPE (n=11), compared with age- and BMI-matched normotensive controls (n=18). The use of plasma samples is able to better reflect the pathogenesis of EOPE and LOPE as systemic conditions centred by widespread endothelial dysfunction.

Dataset Information

Transcription profiling of placenta from women who underwent a normal pregnancy and from those suffering from early or late onset pre-eclampsia

Publications

Microarray analysis of differentially expressed fetal genes in placental tissue derived from early and late onset severe pre-eclampsia.

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