Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA386986 | ENA |
REPOSITORIES: ENA
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Project description:Preeclampsia is a serious pregnancy-induced disorder unique to humans affecting 4.6% of pregnancies worldwide. Advances in the detection, prevention and treatment of preeclampsia have been poor due to our inadequate understanding of its pathogenesis. Here, we perform a multiomics study on early pregnancy placental biopsies (chorionic villus samples) from pregnancies that developed preterm and term preeclampsia compared to normotensive controls. Using an integrative statistical approach we discovered preterm preeclampsia was highly associated with lipoprotein metabolism whereas term preeclampsia was associated with inflammatory pathways and notch signaling. Melanophilin was identified as significantly reduced in early pregnancy placenta from term preeclampsia. Loss of melanophilin was required for syncytialization but excess loss disrupts syncytiotrophoblast function driving the production of antiangiogenic factors known to drive preeclampsia. Our study challenges the dogma that term preeclampsia is not associated with early placental pregnancy dysfunction and provides critical insight into the early pregnancy dysfunction underlying preeclampsia, opening up new avenues for predictive biomarker and preventative treatment discovery.
2026-06-10 | PXD059993 | Pride
Project description:Preeclampsia (PE) is a common pregnancy disorder, and it complicates 5~7% of all pregnancies. At present, termination of pregnancy is the only curative strategy for PE. To explore a potential target for PE treatment, we collected placental tissue samples from patients with preeclampsia (PE) and normal pregnant women (N), and performed high-throughput RNA sequencing. We found that FOXP2 was significantly downregulated in placental samples of patients with PE compared with the controls.
2024-11-06 | GSE279757 | GEO
Project description:Preeclampsia is a serious pregnancy-induced disorder unique to humans affecting 4.6% of pregnancies worldwide. Advances in the detection, prevention and treatment of preeclampsia have been poor due to our inadequate understanding of its pathogenesis. Here, we perform a multiomics study on early pregnancy placental biopsies (chorionic villus samples) from pregnancies that developed preterm and term preeclampsia compared to normotensive controls. Using an integrative multivariate approach, we uncovered distinct molecular signatures: preterm preeclampsia was strongly associated with dysregulated lipoprotein metabolism, while term preeclampsia exhibited alterations in inflammatory pathways, notch signaling and ribosome assembly. These results challenge the prevailing notion that term preeclampsia is unrelated to early placental pregnancy dysfunction. Our study provides critical insights into the early pregnancy aberrations underlying both preterm and term preeclampsia, paving the way for novel predictive biomarker and targeted preventative treatments. This work represents a significant step towards unravelling the complex etiology of preeclampsia and improving maternal and perinatal health outcomes.
2026-06-09 | GSE295760 | GEO
Project description:Background: Hypertensive disorders of pregnancy (HDP) comprise a spectrum of four subtypes: chronic hypertension (cHTN), gestational hypertension (gHTN), preeclampsia (PE), and superimposed preeclampsia (siPE). Although often characterized as a spectrum of disease severity, there have been limited comparative studies of detailed clinical and molecular characteristics of these disorders. We hereby evaluate HDP subtypes using clinical, placental histopathological and molecular data to compare the similarities and differences between HDP subtypes. Methods: We utilize data from over 10-year-long pregnancy cohort with detailed clinical and placental pathology, as well as placental tissue RNA-sequencing. Clinical diagnosis was based on current ACOG criteria, and placental gross and histologic examination was based on the Amsterdam consensus statement. Results: Clinical data analysis showed cHTN and gHTN to be more likely to have normal placental pathology, while PE and siPE were more enriched in maternal vascular malperfusion (MVM). RNA-seq showed distinct gene expression signatures and pathway activation across our HDP subgroups. We could not identify any molecular evidence that preeclampsia (PE or siPE) was an advanced stage of hypertensive disorder (gHTN or cHTN), but rather identified distinct gene expression profiles between these entities, suggesting preeclampsia (PE or siPE) and hypertension (gHTN or cHTN) are distinct pathophysiological conditions. Finally, we found that, in the presence of MVM, siPE and PE share significant gene expression profiles and pathway activation. Conclusion: Our findings suggest that MVM specifically differentiates pregnancies that progress to PE and siPE. MVM is thought to initiate in early gestation, indicating the cascade to PE/siPE maybe differentiated from gHTN/cHTN early in pregnancy. Incorporating placental evaluation into patient care is essential, in order to probe the etiology of HDP.
2026-01-14 | GSE303463 | GEO
Project description:Background: A small number of recent reports have suggested that altered placental DNA methylation may be associated with early onset preeclampsia. It is important that further studies be undertaken to confirm and develop these findings. We therefore undertook a systematic analysis of DNA methylation patterns in placental tissue from 24 women with preeclampsia and 24 with uncomplicated pregnancy outcome. Methods: We analyzed the DNA methylation status of approximately 27,000 CpG sites in placental tissues in a massively parallel fashion using an oligonucleotide microarray. Follow up analysis of DNA methylation at specific CpG loci was performed using the Epityper MassArray approach and high-throughput bisulfite sequencing. Results: Preeclampsia-specific DNA methylation changes were identified in placental tissue samples irrespective of gestational age of delivery. In addition, we identified a group of CpG sites within specific gene sequences that were only altered in early onset-preeclampsia (EOPET) although these DNA methylation changes did not correlate with altered mRNA transcription. We found evidence that fetal gender influences DNA methylation at autosomal loci but could find no clear association between DNA methylation and gestational age. Conclusion: Preeclampsia is associated with altered placental DNA methylation. Fetal gender should be carefully considered during the design of future studies in which placental DNA is analyzed at the level of DNA methylation. Further large-scale analyses of preeclampsia-associated DNA methylation are necessary. Bisulphite converted DNA from the 48 samples were hybridized to the Illumina Infinium 27k Human Methylation Beadchip v1.2
2014-07-12 | E-GEOD-59274 | biostudies-arrayexpress
Project description:The etiology of preeclampsia, a hypertensive disorder of human pregnancy, remains unknown. We addressed fetal sex selection and the suggestive role of fetal HLA-G and related genes, regulating maternal immune responses, in preeclampsia pathogenesis. We assessed birth sex ratios, weights, and seasonality of preeclampsia among 1.79 million births in Finland. We studied haplotypes of HLA-G 3’ untranslated region (UTR), regulating HLA-G expression, in 1000 Genomes series and in a preeclampsia cohort (n=1249). We quantified placental (n=163) mRNA expression of 136 genes, studied HLA-G and IFNα protein expression by immunohistochemistry, and measured maternal and fetal circulating IFNα levels by ELISA. Population-level data showed loss of male fetuses as a characteristic of preeclampsia. As a potential contributor to immune-mediated loss, we found balancing selection at HLA-G 3’UTR modulating sex ratio, and association of HLA-G 3’UTR haplotypes with placental HLA-G expression. HLA-G and its receptors were downregulated in preeclampsia placentas, and surprisingly, interferon alpha-1 (IFNA1) was highly upregulated. IFNA1 and HLA-G distinguished preeclampsia better than placental FLT1 expression. Fetal but not maternal circulating IFNα, produced by trophoblasts, showed association with maternal hypertension and fetal growth restriction. We uncover the link between placental HLA-G expression and human birth sex ratio. We propose that preeclampsia shares, through reduced HLA-G mediated immunotolerance, the mechanism needed to fight placental viral infections and malaria in evolution. IFNα upregulation in preeclampsia placenta, together with its known actions upstream of inflammatory genes, encourages testing IFNα inhibitors and especially the pregnancy-approved antimalarial hydroxichloroquine in treatment of preeclampsia.
2019-11-25 | GSE125460 | GEO
Project description:Preeclampsia is a devastating hypertensive disorder of pregnancy that afflicts between 5-10% of pregnancies in the US, with a higher prevalence in the southern regions of the United States. Black pregnant women are disproportionally at higher risk for preeclampsia onset and severity of disease than other racial groups, including White women. Although this has been recognized in the maternal fetal medicine literature for many years, the underlying mechanism(s) for this racial disparity are unclear. One confounding issue with many studies of racial discrepancies in pregnant women is differences in comorbidities between racial groups. In our current study we were able to obtain a cohort of patients of self-identifying Black or White race that were overall matched for BMI, blood pressure, gestational age and parity and we hypothesized that genetic and placental markers of preeclampsia would be highest in our preeclampsia Black patients compared to healthy patients or White preeclampsia patients. We collected placenta tissue from this cohort of deliveries in Augusta, GA from both healthy and preeclamptic Black and White women (n=13-15). We measured expressions of several preeclampsia-implicated genes, as well as performed a placental morphological analysis and RNA sequencing of a subset of samples. Contrary to our hypothesis, our results from ddPCR analysis of genes associated with preeclampsia risk demonstrated that leptin, preproendothelin-1 (PPET-1) endothelial converting enzyme-1 (ECE-1) and soluble FMS-like tyrosine kinase-1 (sFlt-1) were higher in White preeclamptic women than in Black preeclamptic women. Our RNA sequencing analysis revealed that 136 genes significantly differed between White and Black normal pregnant patients, 288 genes differed between Black healthy and Black preeclampsia patients, while a striking 2394 genes significantly differed between White healthy and White preeclampsia patients and 2346 genes differed between White and Black preeclampsia patients. Placental histology analysis revealed that Black preeclampsia patients demonstrated a lower scoring of morphological pathologies associated with preeclampsia compared to White preeclampsia patients. Collectively, these data indicate that genetic predisposition to preeclampsia in White patients in the placenta differs greatly to that of Black patients, and that placental changes may be more subtle in Black patients that are at high risk for preeclampsia.
2026-07-06 | GSE303840 | GEO
Project description:Aberrant embryo implantation and suboptimal placentation can lead to (severe) complications such as preeclampsia and fetal growth restriction later in pregnancy. Current identification of high-risk pregnancies relies on a combination of risk factors, biomarkers, and ultrasound examinations, a relatively inaccurate approach. Previously, aberrant DNA methylation due to placental hypoxia has been identified as a potential marker of placental insufficiency and, hence, potential (future) pregnancy complications. The goal of the Early Prediction of prEgnancy Complications Testing, or the ExPECT study, is to validate a genome-wide, cell-free DNA (cfDNA) methylation strategy to diagnose preeclampsia accurately. More importantly, the predictive potential of this strategy is also explored to reliably identify high-risk pregnancies early in gestation. Furthermore, a longitudinal study was conducted, including sequential blood samples from pregnant individuals experiencing both uneventful and complicated gestations, to assess the methylation dynamics of cfDNA throughout these pregnancies. This study offers valuable insights into methylation changes at specific genomic regions throughout pregnancy, revealing critical differences between normal and complicated pregnancies. The power of non-invasive cfDNA methylation profiling was successfully proven, suggesting the potential to integrate this non-invasive approach into routine prenatal care. A significant strength of this study is its enzymatic digest, which enriches CpG-rich regions across the genome without the need for proprietary reagents or prior selection of regions of interest. This makes it useful for the cost-effective discovery of novel markers. Investigation of methylation patterns throughout pregnancy showed different methylation trends between unaffected and affected pregnancies. We detected differentially methylated regions (DMRs) in pregnancies complicated with preeclampsia as early as 12 weeks of gestation, with distinct differences in the methylation profile between early and late pregnancy. Two classification models were developed to diagnose and predict preeclampsia, demonstrating promising results on a small set of validation samples.
2026-01-01 | GSE282512 | GEO
Project description:The tubal ectopic pregnancy (TEP) is a severe pregnancy complication accounted for 10-15% pregnancy-related deaths owing to the implantation and growth of embryos in fallopian tubes. Placental villi from TEP exhibit significant difference compared with that from intrauterine pregnancy (IP) in total volumes, trophoblast differentiation and intravillous vascularization. To investigate the difference in expression profiles of placental villi from IP and TEP, placental villi were collected from each phenotype, separated from maternal tissues and analyzed by high-throughput sequencing.
2022-12-10 | GSE210031 | GEO
Project description:The placenta mediates adverse pregnancy outcomes, including preeclampsia, characterized by gestational hypertension and proteinuria. Placental cell type heterogeneity in preeclampsia is not well-understood and limits mechanistic interpretation of bulk gene expression measures. We generated single-cell RNA-sequencing samples for integration with existing data to create the largest deconvolution reference of 19 fetal and 8 maternal cell types from placental villous tissue at term. We deconvoluted eight published microarray case-control studies of preeclampsia. Our findings indicate substantial placental cellular heterogeneity in preeclampsia that predict previously observed bulk gene expression differences. Our deconvolution reference lays the groundwork for cellular heterogeneity-aware investigation into placental dysfunction and adverse birth outcomes.
2022-08-22 | GSE182381 | GEO