A transcriptional profile of the decidua in preeclampsia

Abstract

OBJECTIVE-To obtain insight into possible mechanisms underlying preeclampsia using genome-wide transcriptional profiling in decidua basalis.STUDY DESIGN-Genome-wide transcriptional profiling was performed on decidua basalis tissue from preeclamptic (n = 37) and normal pregnancies (n = 58). 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 <0.05, FDR P <0.1). Both novel (ARL5B, SLITRK4) and previously reported preeclampsiaassociated genes (PLA2G7, HMOX1) 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.

Interplay between Vascular Endothelial Growth Factor (VEGF) and Nuclear Factor Erythroid 2-related Factor-2 (Nrf2)

“…The study used genome-wide transcriptional profiling of preeclamptic and normal pregnancies and showed that the Nrf2-mediated oxidative stress response is overrepresented in preeclampsia (37). Thus, these data strengthen our previous published results (25) and our hypothesis that Nrf2 has a critical role in the etiology and progression of preeclampsia.…”

Identification of ACOX2 as a shared genetic risk factor for preeclampsia and cardiovascular disease

“…However, in other studies, microarrays have been shown to give accurate detection of transcripts with a high correlation to reverse transcription-PCR verifications. 11 The normalization procedure for reverse transcription-PCR uses housekeeping genes whose expression in fact varies dramatically between individuals. 9 Consequently, the normalization carried out for the microarray experiment, based on the average expression level per individual, is likely to be much more accurate.…”

“…Transcriptional profiling was performed on decidua basalis tissues from 37 cases and 58 controls using Illumina Human-6 v.2 Expression BeadChip (Illumina, San Diego, CA, USA) according to Illumina's standard protocols. The sample preparation has been described previously, 11,14 and the data set is available at ArrayExpress (http://www.ebi.ac. uk/microarray-as/ae/) (accession code E-TABM-682).…”

“…9 Many genes have also been identified to be differentially expressed in the placenta or in decidual tissues between women with PE and women with normal pregnancies. [10][11][12] However, it is still unknown whether such differential gene expression is causal or is secondary to the disorder.…”

Increased Heme Oxygenase-1 and Nuclear Factor Erythroid 2-Related Factor-2 in the Placenta Have a Cooperative Action on Preeclampsia

“…Nrf2 has also been shown to play a role in defense mechanisms that protect against effects associated with several toxic intermediates including carcinogenic substances, electrophiles, and reactive oxygen species [14]. Several recent studies have demonstrated that Nrf2 is involved in the etiopathogenesis of PE [15,16,17]. Nrf2 is recognized as an essential upstream transcription factor that regulates HO-1 [18].…”