Differential Gene Expression at the Maternal-Fetal Interface in Preeclampsia Is Influenced by Gestational Age

Lian, Ingrid Alsos; Langaas, Mette; Moses, Eric K.; Johansson, Åsa

doi:10.1371/journal.pone.0069848

Cited by 16 publications

(11 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The top three altered PE pathway categories in the decidual transcriptome were immunity/inflammation, cell signalling and apoptosis, representing 28 altered gene sets, which were consistently altered between both transcriptome profiling batches. These pathway categories are consistent with the published literature [ 24 , 59 ]. The top pathway category of immunity/inflammation supports the growing evidence of a highly dysregulated immune and inflammatory response at the PE maternal-fetal interface [ 60 ].…”

Section: Discussionsupporting

confidence: 92%

Genome-Wide Transcriptome Directed Pathway Analysis of Maternal Pre-Eclampsia Susceptibility Genes

et al. 2015

View full text Add to dashboard Cite

BackgroundPreeclampsia (PE) is a serious hypertensive pregnancy disorder with a significant genetic component. Numerous genetic studies, including our own, have yielded many susceptibility genes from distinct functional groups. Additionally, transcriptome profiling of tissues at the maternal-fetal interface has likewise yielded many differentially expressed genes. Often there is little overlap between these two approaches, although genes identified in both approaches are significantly associated with PE. We have thus taken a novel integrative bioinformatics approach of analysing pathways common to the susceptibility genes and the PE transcriptome.MethodsUsing Illumina Human Ht12v4 and Wg6v3 BeadChips, transcriptome profiling was conducted on n = 65 normotensive and n = 60 PE decidua basalis tissues collected at delivery. The R software package libraries lumi and limma were used to preprocess transcript data for pathway analysis. Pathways were analysed and constructed using Pathway Studio. We examined ten candidate genes, which are from these functional groups: activin/inhibin signalling—ACVR1, ACVR1C, ACVR2A, INHA, INHBB; structural components—COL4A1, COL4A2 and M1 family aminopeptidases—ERAP1, ERAP2 and LNPEP.Results/ConclusionMajor common regulators/targets of these susceptibility genes identified were AGT, IFNG, IL6, INHBA, SERPINE1, TGFB1 and VEGFA. The top two categories of pathways associated with the susceptibility genes, which were significantly altered in the PE decidual transcriptome, were apoptosis and cell signaling (p < 0.001). Thus, susceptibility genes from distinct functional groups share similar downstream pathways through common regulators/targets, some of which are altered in PE. This study contributes to a better understanding of how susceptibility genes may interact in the development of PE. With this knowledge, more targeted functional analyses of PE susceptibility genes in these key pathways can be performed to examine their contributions to the pathogenesis and severity of PE.

show abstract

Section: Discussionsupporting

confidence: 92%

Genome-Wide Transcriptome Directed Pathway Analysis of Maternal Pre-Eclampsia Susceptibility Genes

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Additionally, none of the genes in our study were reported to change expression throughout gestation based on a comparative study conducted by Winn et al [33], which compared gene expression between mid-gestation decidual tissues and term decidual tissues. A recent study, which analysed transcription profiles by merging data from different genome-wide platforms, showed that differential decidual gene expression observed in PE can be influenced by gestational age, highlighting the importance of gestational age matching between sample groups [34]. Their analyses did not show the genes examined in this study to be influenced by gestation [34].…”

Section: Discussionmentioning

confidence: 84%

“…A recent study, which analysed transcription profiles by merging data from different genome-wide platforms, showed that differential decidual gene expression observed in PE can be influenced by gestational age, highlighting the importance of gestational age matching between sample groups [34]. Their analyses did not show the genes examined in this study to be influenced by gestation [34]. All genes ACVR1 , ERAP1 , ERAP2 , LNPEP and COL4A2 differentially expressed in the large set with the exception of INHBB and COL4A1 , were also differentially expressed in the smaller subset, which was gestationally matched, suggesting gestation had no effect on our gene expression and that it is PE state that changes the gene expression.…”

Section: Discussionmentioning

confidence: 99%

Increased decidual mRNA expression levels of candidate maternal pre-eclampsia susceptibility genes are associated with clinical severity

et al. 2014

View full text Add to dashboard Cite

Introduction Pre-eclampsia (PE) has a familial association, with daughters of women who had PE during pregnancy having more than twice the risk of developing PE themselves. Through genome-wide linkage and genetic association studies in PE-affected families and large population samples, we previously identified the following as positional candidate maternal susceptibility genes for PE; ACVR1, INHA, INHBB, ERAP1, ERAP2, LNPEP,COL4A1 and COL4A2. The aims of this study were to determine mRNA expression levels of previously identified candidate maternal pre-eclampsia susceptibility genes from normotensive and severe PE (SPE) pregnancies and correlate mRNA expression levels with the clinical severity of SPE. Methods Third trimester decidual tissues were collected from both normotensive (n=21) and SPE pregnancies (n=24) and mRNA expression levels were determined by real-time PCR. Gene expression was then correlated with several parameters of clinical severity in SPE. Statistical significance was determined by Mann-Whitney U test and Spearman's Correlation. Results The data demonstrate significantly increased decidual mRNA expression levels of ACVR1, INHBB, ERAP1, ERAP2, LNPEP, COL4A1 and COL4A2 in SPE (p<0.05). Increased mRNA expression levels of several genes – INHA, INHBB, COL4A1 and COL4A2 were correlated with earlier onset of PE and earlier delivery of the fetus (p<0.05). Conclusion These results suggest altered expression of maternal susceptibility genes may play roles in PE development and the course of disease severity.

show abstract

“…As the gestational age of LOSPE is more close to that of controls than EOSPE does, we overlapped the DEGs of the two subclasses compared to controls to obtain the key PE-related genes in purpose of minimizing the bias. Compared with the study by Lian et al [2013] who have evaluated the relative effect of gestational age and PE on gene expression via pooling data from three different genomewide transcription studies of the maternal-fetal interface [Winn et al, 2007[Winn et al, , 2009Loset et al, 2011], none of our 22 core regulatory genes are gestational age-associated transcripts. According to the study by Winn et al [2007], two of our 22 core regulatory genes (P4HA1 and GSTO1) are reported to change expression with gestational age, indeed they decrease toward term.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic Profiling in Human Decidua of Severe Preeclampsia Detected by RNA Sequencing

Tong

Zhao

et al. 2017

J of Cellular Biochemistry

View full text Add to dashboard Cite

Maternal decidua plays a critical role in implantation and placentation. Impaired decidualization causes failed intravascular trophoblast invasion and inadequate placentation and then increases the risk of preeclampsia (PE). RNA sequencing (RNA-Seq) has achieved great advances in the characterization and quantification of transcriptomes; is a powerful tool for new transcript discovery, genome annotation, and expression profiling. In the present study, we conducted a RNA-Seq analysis to compare gene expression between decidua of PE (n ¼ 3, early-onset severe PE, EOSPE; n ¼ 3, late-onset severe PE, LOSPE) and normal pregnancies (n ¼ 3). We revealed that decidual gene transcription profile was altered in severe PE and identified 293 key PE-related genes involved in 19 differentially regulated pathways relevant for the pathogenesis of PE, among which ENO2, PGK1, and HK2 involved in glycolysis/gluconeogenesis and HIF-1 signaling pathway which are all highly related with tumorigenesis and are significantly upregulated in cancer cells were severely inhibited in the decidua of PE. Moreover, we identified 22 core regulatory genes, including the newly identified pseudogenes BNIP3P1, HK2P1, and PGK1P1 that encode long non-coding RNA (lncRNA); interestingly, BNIP3/BNIP3P1, HK2/HK2P1, and PGK1/PGK1P1 appear in pairs in core genes. Subsequent analyses using quantitative PCR validated a portion of these results. This study may provide further insight into the mechanisms of PE and function as preventive, predictive, and therapeutic measures. Future functional studies are needed in order to accomplish a greater understanding of the mechanisms involved.

show abstract

Differential Gene Expression at the Maternal-Fetal Interface in Preeclampsia Is Influenced by Gestational Age

Cited by 16 publications

References 37 publications

Genome-Wide Transcriptome Directed Pathway Analysis of Maternal Pre-Eclampsia Susceptibility Genes

Genome-Wide Transcriptome Directed Pathway Analysis of Maternal Pre-Eclampsia Susceptibility Genes

Increased decidual mRNA expression levels of candidate maternal pre-eclampsia susceptibility genes are associated with clinical severity

Transcriptomic Profiling in Human Decidua of Severe Preeclampsia Detected by RNA Sequencing

Contact Info

Product

Resources

About