Integrative Analysis of miRNA and gene Expression Profiles of Early-Onset Preeclampsia
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE177049 | GEO | 2021/06/12
REPOSITORIES: GEO
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Project description:During human pregnancy, placental cytotrophoblasts invade the uterus and its blood vessels, anchoring the progeny and rerouting maternal blood to the embryo/fetus. In preeclampsia, cytotrophoblast invasion is restricted and blood flow to the placenta is reduced. The causes of restricted cytotrophoblast invasion are unknown. Here, preeclampsia and control cytotrophoblasts were cultured for 48 h to allow differentiation/invasion. In various severe forms of preeclampsia ± intrauterine growth restriction, global transcriptional profiling revealed common aberrations in cytotrophoblast gene expression that resolved with culture. Villous cytotrophoblasts were isolated from preeclampsia placentas (PRE, n=5) and placentas of preterm labor patients without signs of infection (PTL, n=5), which served as gestation-matched controls. To better understand the CTB phenotype in the context of PE variants, we included patients with the most clinically significant forms of this condition that necessitated preterm delivery: women with severe PE ± intrauterine growth restrictions, PE with superimposed hypertension and HELLP syndrome (hemolysis, elevated liver enzymes; low platelet count). RNA was purified immediately after the cells were isolated (0 h) and after 12, 24 and 48 h in culture. The relative gene expression across the whole genome was profiled using the Affymetrix HG-U133Plus 2.0 GeneChip platform. Array quality was assesed using RMAExpress. One sample of preterm labor collected at 48h was omitted (39 arrays total). We used both LIMMA and maSigPro (R/Bioconductor) to determine differentially expressed genes.
2012-08-17 | E-GEOD-40182 | biostudies-arrayexpress
Project description:Background: Early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE) has been regarded as two different phenotypes with heterogeneous manifestation. The underlying mechanisms remain elusive. Aim to gain insight into the pathogenesis of the two traits, we analyzed the placental gene expression profiles in preeclampsia placentas. Methods: Whole genome-wide microarray was used to describe the gene expression profiles in the placenta tissues from patients with early-(n=7; <34 weeks), late-onset(n=8; >36 weeks) PE and their controls who delivered preterm (n=5;<34 weeks) or at term(n=5; >36 weeks) Genes were selected as differentially expressed upon a fold-changeâ?¥2 and q-value<0.05. qRT-PCR was undertaken to verify the results. Western blot was further performed to verify secreted genes at the protein level. Results: A total of 627 genes were differentially expressed in early-compared with late-onset PE. Of these, 177 genes were up-regulated and 450 genes down-regulated in early-onset PE. Go analysis showed significant alteration in several biological processes, in addition to the processes which have been found before, such as immune and inflammatory response, cell adhension, female pregnancy and blood vessel development. We also found alteration in G-protein coupled receptor protein signaling pathway, G protein-coupled receptor 124 (GPR124) (P=0.0064) and MAS-related GPR, member F (MRGPRF)(P=0.0155 ) were both down-regulated obviously in early-onset PE. Conclusion: The different gene expression profiles suggested early- and late-onset PE are separate disease entities. Moreover, G-protein coupled receptor protein signaling pathway may contribute to the mechanism underlying early- and late-onset preeclampsia. Whole genome-wide microarray was used to describe the gene expression profiles in the placenta tissues from patients with early-(n=7; <34 weeks), late-onset (n=8; >36 weeks) PE and their controls who delivered preterm(n=5;<34 weeks) or at term(n=5; >36 weeks). Pooled controls who delivered at term were labled with cy5.
2015-10-27 | E-GEOD-74341 | biostudies-arrayexpress
Project description:Preeclampsia is a severe placenta-related pregnancy disorder that is generally divided into two subtypes named early-onset preeclampsia (onset <34 weeks of gestation), and lateonset preeclampsia (onset ≥34 weeks of gestation), with distinct pathophysiological origins. Both forms of preeclampsia have been associated with maternal systemic inflammation. However, alterations in the placental immune system have been less well characterized. Here, we studied immunological alterations in early- and late-onset preeclampsia placentas using a targeted expression profile approach. RNA was extracted from snap-frozen placenta samples (healthy n=13, early-onset preeclampsia n=13, and late-onset preeclampsia n=6). The expression of 730 immune-related genes from the Pan Cancer Immune Profiling Panel was measured, and the data were analyzed Q10 in the advanced analysis module of nSolver software (NanoString Technology). The results showed that early-onset preeclampsia placentas displayed reduced expression of complement, and toll-like receptor (TLR) associated genes, specifically TLR1 and TLR4. Mast cells and M2 macrophages were also decreased in early-onset preeclampsia compared to healthy pl acentas. The findings were confirmed by an immunohistochemistry approach using 20 healthy, 19 early-onset preeclampsia, and 10 late-onset preeclampsia placentas. We conclude that the placental innate immune system is altered in early-onset preeclampsia compared to uncomplicated pregnancies. The absence of these alterations in late-onset preeclampsia placentas indicates dissimilar immunological profiles. The study revealed distinct pathophysiological processes in earlyonset and late-onset preeclampsia placentas and imply that a tailored treatment to each subtype is desirable.
2021-12-13 | GSE190639 | GEO
Project description:Background: Long non-coding RNAs (lncRNAs) are an important class of pervasive genes involved in a variety of biological functions. They are aberrantly expressed in many types of diseases. We want to study the lncRNAs profiles in preeclampsia. Preeclampsia has been observed in patients with molar pregnancy where a fetus is absent demonstrating that the placenta is sufficient to cause the condition. So we analyze the lncRNAs profiles in preeclampsia placentas. In this study, we described the lncRNAs profiles in 6 preeclampsia placentas (T) and 5 matched normal pregnancy placentas (N) tissues by microarray. Methodology/Principal Findings: With abundant and varied probes accounting 33,045 LncRNAs in our microarray, the number of lncRNAs that expressed at a certain level could be detected is 28,443. From the data we found there were 738 lncRNAs that differentially expressed (M-bM-^IM-%1.5 fold-change) among preeclampsia placentas compared with matched controls. Up to 18,063 coding transcripts could be detected in placenta samples through 30,215 coding transcripts probes. Coding-non-coding gene co-expression networks (CNC network) were constructed based on the correlation analysis between the differential expressed lncRNAs and mRNAs. According to the GO-Pathway analysis of differential expressed lncRNAs/mRNAs, we choose three lncRNAs to analyze the relationship between lncRNAs and preeclampsia. LOC391533, LOC284100, CEACAMP8 were evaluated by qPCR in 40 of preeclampsia placentas and 40 of controls. The results showed three lncRNAs were aberrantly expressed in preeclampsia placentas compared with controls. Conclusions/Significance: Our study is the first one to determine genome-wide lncRNAs expression patterns in preeclampsia placenta by microarray. The results displayed that clusters of lncRNAs were aberrantly expressed in preeclampsia placenta compared with controls, which revealed that lncRNAs differentially expressed in preeclampsia placenta may exert a partial or key role in preeclampsia development. Misregulation of LOC391533, LOC284100, CEACAMP8 might be associated with preeclampsia. Taken together, this study may provide potential targets for future treatment of preeclampsia and novel insights into preeclampsia biology. LncRNAs/mRNAs profiles in 6 preeclampsia placentas and 5 matched normal pregnancy placentas tissues by microarray using Arraystar v2.0.
2013-09-12 | E-GEOD-50783 | biostudies-arrayexpress
Project description:Preeclampsia (PE), a hypertensive disorder of pregnancy, is hypothesized to be associated with, if not mechanistically related to abnormal placental function. However, the exact mechanisms regulating the pathogenesis of PE remain unclear. While many studies have investigated changes in gene expression in the PE placenta, the role of epigenetics in PE associated placental dysfunction remains unclear. Using the genome-wide Illumina Infinium Methylation 450 BeadChip array, we analyzed gene-specific alterations in DNA methylation in placental biopsies collected from normal pregnant women delivering at term (n=14), with term PE (≥37 weeks; n=19) or with preterm PE (<37 weeks, n=12). Of the 485,582 gene loci on the array, compared to controls, 229 loci were differentially methylated in PE placentas and 3411 loci were differentially methylated in preterm PE (step up p-value <0.05 and >5% methylation difference). Functional annotation of the differentially methylated genes in preterm PE placentas revealed a 32 gene cluster in the cadherin and cell adhesion functional groups (Benjamini p<0.00001). Hypermethylation of CDH11 (p=0.0143), COL5A1 (p=0.0127) and TNF (p=0.0098) and hypomethylation of NCAM1 (p=0.0158) was associated with altered mRNA expression in preterm PE placentas. These studies demonstrate aberrant methylation, correlating with disease severity, in PE placentas. Bisulphite converted DNA from the 45 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip v1.2
2014-05-20 | E-GEOD-57767 | biostudies-arrayexpress
Project description:Introduction: To determine the miRNA expression profile in placentas complicated by Preeclampsia (PE) and compare it to uncomplicated pregnancies. Methods: Sixteen placentas from women with PE, including 11 with early onset PE (EOPE) and 5 with late onset PE (LOPE), as well as 8 from uncomplicated pregnancies were analyzed using miRNA microarrays. For statistical analyses the MATLAB® simulation environment was applied. The over-expression of miR-518a-5p was verified using Quantitative Real-Time Polymerase Chain Reaction. Results: Overall, 44 miRNAs were found deregulateddysregulated in PE complicated placentas. Statistical analysis revealed that miR-431, miR-518a-5p and miR-124* were over-expressed in EOPE complicated placentas as compared to controls whereas miR-544 and miR-3942 were down-regulated in EOPE. When comparing the miRNA expression profile in cases with PE and PE- growth restricted fetuses (FGR), miR-431 and miR-518a-5p were found over-expressed in pregnancies complicated by FGR. Additionally, up- regulation of miR-124, miR-423-3p and miR-518a-5p was associated with proteinuria. Discussion: Specific miRNAs can differentiate EOPE and LOPE from uncomplicated pregnancies representing putative PE-specific diagnostic biomarkers. Among them, miR-518a-5p emerged as a potential diagnostic indicator for EOPE cases as well as for FGR and proteinuria associated PE complicated placentas designating its potential link to the severity of the disease.
2017-09-07 | GSE103542 | GEO
Project description:Introduction. Preeclampsia (PE) carries increased risks of cardiovascular- and metabolic diseases in mothers and offspring during the life course. While the severe early-onset PE (EOPE) phenotype originates from impaired placentation in early pregnancy, late-onset PE (LOPE) is in particular associated with pre-existing maternal cardiovascular- and metabolic risk factors. We hypothesize that PE is associated with altered epigenetic programming of placental and fetal tissues and that these epigenetic changes might elucidate the increased cardiovascular- and metabolic disease susceptibility in PE offspring. Methods. A nested case-control study was conducted in The Rotterdam Periconceptional Cohort comprising 13 EOPE, 16 LOPE, and three control groups of 36 uncomplicated pregnancies, 27 normotensive fetal growth restricted (FGR) and 20 normotensive preterm birth (PTB) complicated pregnancies. Placental tissue, newborn umbilical cord blood leucocytes (UC-WBC) and umbilical vein endothelial cells (HUVEC) were collected and DNA methylation of cytosine-guanine dinucleotides was measured by the Illumina HumanMethylation450K BeadChip. An epigenome-wide analysis was performed by using multiple linear regression models. Results. Epigenome-wide tissue-specific analysis between EOPE and PTB controls revealed 5001 mostly hypermethylated differentially methylated positions (DMPs) in UC-WBC and 869 mostly hypomethylated DMPs in placental tissue, situated in or close to genes associated with cardiovascular-metabolic developmental pathways. Discussion. This study shows differential methylation in UC-WBC and placental tissue in EOPE as compared to PTB, identifying DMPs that are associated with cardiovascular system pathways. Future studies should examine these loci and pathways in more detail to elucidate the associations between prenatal PE exposure and the cardiovascular disease risk in offspring.
2017-09-06 | GSE103253 | GEO
Project description:Preeclampsia (PE) is a serious pregnancy associated disorder. Recently, it has been proposed that the role of the placenta differ between the two sub-groups early- and late-onset PE. To further elucidate differences between the two sub-groups, we conducted transcriptional profiling of human placenta comparing early- with late-onset PE. The analysis showed differences in angiogenesis associated genes. Two-condition experiment, early-onset PE (n=8) vs. late-onset PE (n=7).
2011-02-28 | E-GEOD-22526 | biostudies-arrayexpress
Project description:Background: Early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE) has been regarded as two different phenotypes with heterogeneous manifestation. The underlying mechanisms remain elusive. Aim to gain insight into the pathogenesis of the two traits, we analyzed the placental gene expression profiles in preeclampsia placentas. Methods: Whole genome-wide microarray was used to describe the gene expression profiles in the placenta tissues from patients with early-(n=7; <34 weeks), late-onset(n=8; >36 weeks) PE and their controls who delivered preterm (n=5;<34 weeks) or at term(n=5; >36 weeks) Genes were selected as differentially expressed upon a fold-change≥2 and q-value<0.05. qRT-PCR was undertaken to verify the results. Western blot was further performed to verify secreted genes at the protein level. Results: A total of 627 genes were differentially expressed in early-compared with late-onset PE. Of these, 177 genes were up-regulated and 450 genes down-regulated in early-onset PE. Go analysis showed significant alteration in several biological processes, in addition to the processes which have been found before, such as immune and inflammatory response, cell adhension, female pregnancy and blood vessel development. We also found alteration in G-protein coupled receptor protein signaling pathway, G protein-coupled receptor 124 (GPR124) (P=0.0064) and MAS-related GPR, member F (MRGPRF)(P=0.0155 ) were both down-regulated obviously in early-onset PE. Conclusion: The different gene expression profiles suggested early- and late-onset PE are separate disease entities. Moreover, G-protein coupled receptor protein signaling pathway may contribute to the mechanism underlying early- and late-onset preeclampsia.
2015-10-27 | GSE74341 | GEO
Project description:Preeclampsia (PE), a hypertensive disorder of pregnancy, is hypothesized to be associated with, if not mechanistically related to abnormal placental function. However, the exact mechanisms regulating the pathogenesis of PE remain unclear. While many studies have investigated changes in gene expression in the PE placenta, the role of epigenetics in PE associated placental dysfunction remains unclear. Using the genome-wide Illumina Infinium Methylation 450 BeadChip array, we analyzed gene-specific alterations in DNA methylation in placental biopsies collected from normal pregnant women delivering at term (n=14), with term PE (≥37 weeks; n=19) or with preterm PE (<37 weeks, n=12). Of the 485,582 gene loci on the array, compared to controls, 229 loci were differentially methylated in PE placentas and 3411 loci were differentially methylated in preterm PE (step up p-value <0.05 and >5% methylation difference). Functional annotation of the differentially methylated genes in preterm PE placentas revealed a 32 gene cluster in the cadherin and cell adhesion functional groups (Benjamini p<0.00001). Hypermethylation of CDH11 (p=0.0143), COL5A1 (p=0.0127) and TNF (p=0.0098) and hypomethylation of NCAM1 (p=0.0158) was associated with altered mRNA expression in preterm PE placentas. These studies demonstrate aberrant methylation, correlating with disease severity, in PE placentas.
2014-05-20 | GSE57767 | GEO