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.
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).
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.
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.
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.
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.
Project description:This SuperSeries is composed of the following subset Series: GSE36812: Epigenome analysis of cord blood samples from newborns GSE36828: Genome-wide analysis of gene expression levels in placenta and cord blood samples from newborns babies GSE36829: Epigenome analysis of placenta samples from newborns GSE36852: Epigenome analysis of newborn placenta and cord blood samples Refer to individual Series