Dataset Information

A transcriptional profile of the decidua in preeclampsia.

ABSTRACT:

Objective

We sought to obtain insight into possible mechanisms underlying preeclampsia using genomewide transcriptional profiling in decidua basalis.

Study design

Genomewide transcriptional profiling was performed on decidua basalis tissue from preeclamptic (n = 37) and normal (n = 58) pregnancies. Differentially expressed genes were identified and merged into canonical pathways and networks.

Results

Of the 26,504 expressed transcripts detected, 455 were differentially expressed (P < .05; false discovery rate, P < .1). Both novel (ARL5B, SLITRK4) and previously reported preeclampsia-associated (PLA2G7, HMOX1) genes were identified. Pathway analysis revealed that tryptophan metabolism, endoplasmic reticulum stress, linoleic acid metabolism, notch signaling, fatty acid metabolism, arachidonic acid metabolism, and NRF2-mediated oxidative stress response were overrepresented canonical pathways.

Conclusion

In the present study single genes, canonical pathways, and gene-gene networks that are likely to play an important role in the pathogenesis of preeclampsia have been identified. Future functional studies are needed to accomplish a greater understanding of the mechanisms involved.

SUBMITTER: Loset M

PROVIDER: S-EPMC3011026 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Publications

A transcriptional profile of the decidua in preeclampsia.

Løset Mari M Mundal Siv B SB Johnson Matthew P MP Fenstad Mona H MH Freed Katherine A KA Lian Ingrid A IA Eide Irina P IP Bjørge Line L Blangero John J Moses Eric K EK Austgulen Rigmor R

American journal of obstetrics and gynecology 20110101 1

<h4>Objective</h4>We sought to obtain insight into possible mechanisms underlying preeclampsia using genomewide transcriptional profiling in decidua basalis.<h4>Study design</h4>Genomewide transcriptional profiling was performed on decidua basalis tissue from preeclamptic (n = 37) and normal (n = 58) pregnancies. Differentially expressed genes were identified and merged into canonical pathways and networks.<h4>Results</h4>Of the 26,504 expressed transcripts detected, 455 were differentially expr ...[more]

PMID: 20934677

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Project description:To compare the clinical characteristics and outcomes of preeclamptic women presenting with a normal plasma angiogenic profile with those subjects who are characterized by an abnormal angiogenic profile.This was a secondary analysis of a prospective cohort study in women presenting to obstetrical triage at <37 weeks of gestation and diagnosed with preeclampsia within 2 weeks of enrollment and in whom angiogenic factors (sFlt1 and PlGF) measurements were available. Patients were divided into two groups based on their circulating levels of these factors described as a ratio; the sFlt1/PlGF ratio, non-angiogenic preeclampsia (sFlt1/PlGF ratio <85) and angiogenic preeclampsia (sFlt1/PlGF ratio ?85). The data are presented by sFlt1/PlGF category using median and quartile 1-quartile 3 for continuous variables and by frequency and sample sizes for categorical variables.In our cohort, the patients with non-angiogenic preeclampsia (N?=?46) were more obese [BMI: 35.2 (31.6, 38.7) versus 31.1 (28.0, 39.0), p?=?0.04], more likely to have preexisting diabetes (21.7% versus 2.0%, p?=?0.002) and presented at a later gestational age [35 (32, 37) versus 32 (29, 34) weeks, p?<?0.0001] as compared with women with angiogenic preeclampsia (N?=?51). Women with non-angiogenic preeclampsia had no serious adverse outcomes (elevated liver function tests/low platelets: 0% versus 23.5%, abruption: 0% versus 9.8%, pulmonary edema: 0% versus 3.9%, eclampsia: 0% versus 2.0 %, small for gestational age: 0% versus 17.7% and fetal/neonatal death: 0% versus 5.9%) as compared with women with angiogenic preeclampsia. The rate of preterm delivery <34 weeks was 8.7% in non-angiogenic preeclampsia compared with 64.7% in angiogenic preeclampsia (p?<?0.0001). Interestingly, delivery between 34 and 37 weeks and resource utilization (hospital admission days) were similar in the two groups.In contrast to the angiogenic form, the non-angiogenic form of preeclampsia is characterized by little to no risk of preeclampsia-related adverse outcomes, other than iatrogenic prematurity. Incorporation of angiogenic biomarkers in the evaluation of preeclampsia may allow accurate and early identification of severe disease.

Project description:Background:Preeclampsia (PE) is a heterogeneous, hypertensive disorder of pregnancy, with no robust biomarkers or effective treatments. We hypothesized that this heterogeneity is due to the existence of multiple subtypes of PE and, in support of this hypothesis, we recently identified five clusters of placentas within a large gene expression microarray dataset (N?=?330), of which four (clusters 1, 2, 3, and 5) contained a substantial number of PE samples. However, while transcriptional analysis of placentas can subtype patients, we propose that the addition of epigenetic information could discern gene regulatory mechanisms behind the distinct PE pathologies, as well as identify clinically useful potential biomarkers. Results:We subjected 48 of our samples from transcriptional clusters 1, 2, 3, and 5 to Infinium HumanMethylation450 arrays. Samples belonging to transcriptional clusters 1-3 still showed visible relationships to each other by methylation, but cluster 5, with known chromosomal abnormalities, no longer formed a cohesive group. Within transcriptional clusters 2 and 3, controlling for fetal sex and gestational age in the identification of differentially methylated sites, compared to the healthier cluster 1, dramatically reduced the number of significant sites, but increased the percentage that demonstrated a strong linear correlation with gene expression (from 5% and 2% to 9% and 8%, respectively). Locations exhibiting a positive relationship between methylation and gene expression were most frequently found in CpG open sea enhancer regions within the gene body, while those with a significant negative correlation were often annotated to the promoter in a CpG shore region. Integrated transcriptome and epigenome analysis revealed modifications in TGF-beta signaling, cell adhesion, oxidative phosphorylation, and metabolism pathways in cluster 2 placentas, and aberrations in antigen presentation, allograft rejection, and cytokine-cytokine receptor interaction in cluster 3 samples. Conclusions:Overall, we have established DNA methylation alterations underlying a portion of the transcriptional development of "canonical" PE in cluster 2 and "immunological" PE in cluster 3. However, a significant number of the observed methylation changes were not associated with corresponding changes in gene expression, and vice versa, indicating that alternate methods of gene regulation will need to be explored to fully comprehend these PE subtypes.

Dataset Information

A transcriptional profile of the decidua in preeclampsia.

Objective

Study design

Results

Conclusion

Publications

A transcriptional profile of the decidua in preeclampsia.

Similar Datasets

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