Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “pre-eclampsia”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2025

Role of oxysterol 4β-hydroxycholesterol and liver X receptor alleles in pre-eclampsia.

BACKGROUND: Liver X receptors (LXRs) are expressed in placenta and may be associated with pre-eclampsia (PE). Oxysterols act as agonists for LXRs. We recently proposed a new blood pressure-regulating circuit with oxysterol 4β-hydroxycholesterol (4βHC) acting as a hypotensive factor via LXRs. MATERIALS AND METHODS: This study investigated the association between maternal plasma 4βHC, blood pressure (BP) indices, placental expression of LXR target genes, and patient characteristics using data from the Finnish Genetics of Pre-Eclampsia Consortium (FINNPEC) cohort. Plasma samples of 144 women with PE and 38 healthy pregnant controls as well as 44 PE and 40 control placental samples were available. In addition, genetic data from the FinnGen project was utilized to explore the associations of LXR alleles with PE and pregnancy hypertension. RESULTS: There were no significant associations between 4βHC and BP or maternal and perinatal characteristics in FINNPEC cohort. However, plasma 4βHC was inversely correlated with the maternal body mass index. There were no associations with the genetic variants of LXRs with PE in FinnGen. LXR target genes APOD, SCARB1, TGM2, and LPCAT3 were expressed differently between PE and normal pregnancies in placental samples of FINNPEC. CONCLUSIONS: Our results demonstrate that plasma 4βHC and genetic LXR variants do not play a major role in PE and BP regulation during pregnancy. However, key LXR target genes involved in lipid metabolism were expressed differently in normal and PE pregnancies. Further research is needed to understand the complexities of oxysterols, LXRs, and their potential contributions to placental function and pregnancy outcomes.

Humans↗
PubMed2025

Maternal-Foetal HLA-DQB1 Incompatibility Is Associated With Pregnancy-Induced Hypertensive Disorders in a Genetically Isolated Population.

In pregnancy, semi-allogenic foetal trophoblasts express a specific HLA profile mediating maternal leukocyte contact, crucial for placentation. Paradoxically, maternal immunomodulation requires foetal antigen recognition, especially involving certain HLA molecules. Pre-eclampsia, a severe hypertensive complication, has been linked to antigenic similarity. Previously, we showed no selection for HLA (in)compatibility in uncomplicated naturally conceived pregnancies. However, pre-eclamptic pregnancies were associated with increased total maternal-foetal HLA and HLA-C matching. These associations suggest a role for HLA mismatches in immune regulation leading to an uncomplicated pregnancy. To better understand HLA homozygosity in human reproduction, we aimed to determine if there is a preferential selection for HLA compatibility in a genetically isolated population, and its relation to hypertensive complications. A nested case-control study, comprising 125 uncomplicated pregnancies and 50 with hypertensive complications (29 with pregnancy-induced hypertension, 21 with pre-eclampsia) was conducted in a genetically isolated Dutch population (FROH 1.3-3.1). Maternal and foetal HLA-A, -B, -C, -DRB1, -DQA1, -DQB1 and maternal killer-cell immunoglobulin-like receptor (KIR) genotyping were performed. Maternal-foetal HLA (mis)match counts were compared to expected values from randomisation of paternal HLA haplotypes over maternal haplotypes of the foetuses. Mismatched CD4+ T cell epitopes presented by maternal HLA class II were predicted using the PIRCHE-II algorithm. In uncomplicated pregnancies, no difference was found between observed and expected maternal-foetal HLA (mis)matches. However, pregnancies with hypertensive complications showed significantly higher observed HLA-DQB1 mismatches, reflected in PIRCHE-II scores. No significant differences were found in KIR/HLA-C frequencies. Interpretation is limited by the small sample size and the grouping of distinct hypertensive disorders. Nonetheless, maternal-foetal HLA-DQB1 mismatch seems to play a role in the aetiology of hypertensive complications during pregnancy in this population.

Humans↗
PubMed2026

Autophagy in the Regulation of Placental Development: From Trophoblast Differentiation to Metabolic Stress Adaptation.

Successful pregnancy depends on precise placental development, where trophoblast differentiation, syncytialization, invasion, and adaptation to metabolic stress are critical. Autophagy, a lysosome-mediated degradation pathway, has emerged as an important regulator of cellular homeostasis, yet its integrated role in trophoblast fate and functions has not been comprehensively summarised. This review synthesises current evidence on autophagy's functions throughout placentation, from trophoblast differentiation to syncytialization and extravillous trophoblast invasion. We examine how autophagy enables cellular remodelling during differentiation, supports metabolic adaptation under hypoxia and nutrient stress, and maintains mitochondrial quality control through selective mitophagy. Autophagy is essential for syncytiotrophoblast formation via endoplasmic reticulum stress-coordinated activation and p53 downregulation. However, its effects on trophoblast invasion are context-dependent, influenced by oxygen tension, autophagic flux completeness, and differentiation state, which can potentially be shaped by parent-offspring genetic conflicts through genomic imprinting. Both excessive and insufficient autophagy contribute to pregnancy complications, including pre-eclampsia, foetal growth restriction, gestational diabetes mellitus, preterm birth, recurrent spontaneous abortion and obstetric antiphospholipid syndrome through distinct molecular mechanisms. Autophagy functions as a dynamically tuned homeostatic mechanism in placental development. Understanding condition-specific autophagy dysregulation is thereby crucial for improving pregnancy outcomes.

Autophagy↗
PubMed2025

PLSKO: a robust knockoff generator to control false discovery rate in omics variable selection.

MOTIVATION: Integrating the knockoff framework with any variable-selection method delivers stringent false discovery rate (FDR) control without recourse to p-values, offering a powerful alternative for differential expression analysis of high-throughput omics datasets. However, existing knockoff generators rely on restrictive modelling assumptions or coarse approximations that often inflate the FDR when applied to real-world data. RESULTS: We introduce Partial Least Squares Knockoff (PLSKO), an efficient, assumption-free generator that remains robust across diverse omics platforms. Our extensive simulations show that PLSKO is the only method to maintain FDR control with sufficient power in complex non-linear settings. Our semi-simulation studies drawn from RNA-seq, proteomics, metabolomics, and microbiome experiments confirm PLSKO generates valid knockoff variables. In pre-eclampsia multi-omics case studies, we combine PLSKO with Aggregation Knockoff to address the randomness of knockoffs and improve power, and demonstrate the method's ability to recover biologically meaningful features. AVAILABILITY AND IMPLEMENTATION: Our proposed algorithm is available on Github (https://github.com/guannan-yang/PLSKO) and Zenodo (https://doi.org/10.5281/zenodo.16879594).

Algorithms↗
PubMed1976

Fetal heart rate and fetal movements.

Fetal Heart Rate (F.H.R.) in association with fetal movement was evaluated in 141 normal and pathological pregnancies. In the normal cases only 31% showed an acceleration of F.H.R. in association with fetal movement. The majority of the normal cases, 62%, did not demonstrate changes in F.H.R. in association with fetal movement. In the pathological pregnancies there were no characteristic changes in F.H.R. associated with fetal movement. It appears that F.H.R. acceleration associated with fetal movement cannot be used as an index for fetal well being.

Female↗
PubMed1976

Ritodrine hydrochloride induced cardiopulmonary and placental hemodynamic changes in normal and hypertensive late pregnancy.

Cardiopulmonary parameters (minute volume, heart rate, stroke volume, right heart, pulmonary and left heart blood volumes), blood pressure and placental blood flow were evaluated in 20 normal patients, nine patients with preeclamptic disease and 12 with essential hypertension in late pregnancy before and 60 minutes after a single i.m. dose of 10 mg of ritodrine hydrochloride. The drug caused a statistically significant increase in heart rate in all the patient groups, while the systolic and diastolic blood pressures were only slightly affected. Minute volume was unchanged in the group of normal patients, but in both hypertensive groups there was a significant increase. The placental perfusion index was statistically nearly significantly decreased in the group of uncomplicated pregnancies, statistically significantly increased in preeclamptic patients, and not affected in the group with essential hypertension. Ritodrine hydrochloride medication can be expected to have a positive effect on placental blood flow only in preeclamptic disease, and then probably in the milder forms of the disease.

Female↗
PubMed2024

Systematic Proteome Profiling of Maternal Plasma for Development of Preeclampsia Biomarkers.

Preeclampsia (PE) is a hypertensive disorder of pregnancy with various clinical symptoms. However, traditional markers for the disease including high blood pressure and proteinuria are poor indicators of the related adverse outcomes. Here, we performed systematic proteome profiling of plasma samples obtained from pregnant women with PE to identify clinically effective diagnostic biomarkers. Proteome profiling was performed using TMT-based liquid chromatography-mass spectrometry (LC-MS/MS) followed by subsequent verification by multiple reaction monitoring (MRM) analysis on normal and PE maternal plasma samples. Functional annotations of differentially expressed proteins (DEPs) in PE were predicted using bioinformatic tools. The diagnostic accuracies of the biomarkers for PE were estimated according to the area under the receiver-operating characteristics curve (AUC). A total of 1307 proteins were identified, and 870 proteins of them were quantified from plasma samples. Significant differences were evident in 138 DEPs, including 71 upregulated DEPs and 67 downregulated DEPs in the PE group, compared with those in the control group. Upregulated proteins were significantly associated with biological processes including platelet degranulation, proteolysis, lipoprotein metabolism, and cholesterol efflux. Biological processes including blood coagulation and acute-phase response were enriched for down-regulated proteins. Of these, 40 proteins were subsequently validated in an independent cohort of 26 PE patients and 29 healthy controls. APOM, LCN2, and QSOX1 showed high diagnostic accuracies for PE detection (AUC >0.9 and p&#xa0;<&#xa0;0.001, for all) as validated by MRM and ELISA. Our data demonstrate that three plasma biomarkers, identified by systematic proteomic profiling, present a possibility for the assessment of PE, independent of the clinical characteristics of pregnant women.

Humans↗
PubMed2026

Changes of DNA methylation and gene expression profile in placental villi and chorioamniotic membranes under preeclampsia.

BACKGROUND: Preeclampsia (PE) is a serious pregnancy complication with elusive pathogenesis. Although epigenetic dysregulation is implicated, its layer-specific placental roles are poorly defined. This study aimed to identify shared and layer-specific epigenetic alterations in PE by profiling DNA methylation and gene expression in placental villi (PV) and chorioamniotic membranes (CAM). RESEARCH DESIGN AND METHODS: PV and CAM samples were collected from 7 normal and 8 PE pregnancies, and three public DNA methylation datasets (GSE98224, GSE44667, GSE75196) were integrated. Differentially methylated genes (DMGs) and differentially expressed genes (DEGs) were identified based on whole-genome methylation and transcriptome sequencing. Layer-specific and shared gene sets were identified by cross-analysis, with functional annotation using Gene Ontology (GO). RESULTS: EM-seq revealed a hypermethylation-dominant, tissue-specific methylation landscape in PE placentas. Cross-tissue comparison identified shared DMGs between the two layers, including nine key genes consistently altered in public datasets. Integrated analysis in PV further identified 22 co-dysregulated genes, enriched in thermoregulation, maternal-fetal immunity, signal transduction, and cell differentiation. CONCLUSIONS: This study elucidates the shared and layer-specific dysregulation of gene networks at methylomic and transcriptomic levels in PE placenta. Comparing PV and CAM highlights placental epigenetic heterogeneity and dysfunction, offering novel clues for mechanistic research and layer-targeted therapies.

Humans↗
PubMed2025

Investigations of HLA-F and HLA-G 3'UTR Polymorphisms in Preeclampsia and Fetal Growth Restriction Indicate a Possible Role of HLA-F-HLA-G Haplotypes and Diplotypes.

HLA-F and HLA-G may be involved in the pathogeneses of preeclampsia and fetal growth restriction (FGR). However, the functions of HLA-F and HLA-G in placental dysfunction remain unclear. The aim was to investigate differences in the prevalence of specific HLA-F and HLA-G gene allelic polymorphisms, genotypes, haplotypes, and diplotypes between controls and cases with preeclampsia or FGR. In total, blood samples from 365 pregnant females (controls, n&#x2009;=&#x2009;192; preeclampsia, n&#x2009;=&#x2009;164; FGR, n&#x2009;=&#x2009;19) in their second and third trimester, and corresponding cordial blood samples (reflecting newborns, n&#x2009;=&#x2009;160) were obtained after delivery. Genomic DNA was sequenced with a focus on the specific gene polymorphisms in the HLA-F gene locus, especially the single nucleotide polymorphisms (SNPs) rs1362126 (G/A), rs2523405 (T/G) and rs2523393 (A/G), as well as the rs371194629 (14-bp ins/del) in the 3'UTR of HLA-G. Haplotype and diplotype distributions were obtained using PHASE v2.1, and linkage disequilibrium analyses were performed. SNPs in the HLA-F gene locus and the 3'UTR of HLA-G were not associated with the risk of preeclampsia or FGR. The SNPs did not correlate with fetal-placental weight ratio, deviation of birth weight at gestational age, and placental weight. However, a trend towards an absence of certain HLA-F-HLA-G extended diplotypes in preeclampsia was observed. The current study does not support associations of the investigated HLA-F SNPs with preeclampsia or FGR. However, further studies are needed to evaluate the possible role of certain fetal HLA-F-HLA-G extended haplotypes and diplotypes in preeclampsia.

Humans↗
PubMed2026

Maternal and Fetal HLA Heterozygosity in Preeclampsia: Insights From a Large Multi-Ancestry Pregnancy Cohort.

Preeclampsia (PE) is a leading cause of maternal and neonatal morbidity, with immune dysregulation at the maternal-fetal interface central to its pathogenesis. The highly polymorphic HLA region mediates maternal immune tolerance of the semi-allogeneic fetus, yet the contribution of HLA diversity to PE risk remains poorly defined. Whether the HLA heterozygote advantage observed in other immune disorders is relevant to PE has not been systematically evaluated. Using data from the multi-ancestry TOPMed Boston-Colombia Collaborative for Adverse Pregnancy Outcomes (n&#x2009;=&#x2009;12,790; 4770 PE, 8020 controls; 10,808 maternal, 1982 fetal, including 1848 pairs), we evaluated associations between heterozygosity across eight classical HLA loci and PE and four sub-phenotypes, adjusting for genetic ancestry. HLA heterozygosity was common across most loci (>&#x2009;80%). No individual maternal HLA locus was associated with overall PE; however, heterozygosity across Class I loci showed a protective effect in preterm PE (OR&#x2009;=&#x2009;0.81, 95% CI: 0.68-0.97), with a similar pattern for HLA-A heterozygosity (OR&#x2009;=&#x2009;0.78, 95% CI: 0.64-0.97). In contrast, fetal heterozygosity at HLA-DQB1 was nominally associated with increased risk of PE (OR&#x2009;=&#x2009;1.36, 95% CI: 1.03-1.80) and preterm PE (OR&#x2009;=&#x2009;1.73, 95% CI: 1.13-2.74). No individual maternal or fetal HLA alleles were associated with PE. Maternal-fetal mismatch analysis demonstrated locus-specific associations with preterm PE, including increased risk with HLA-DQA1 mismatch and reduced risk with HLA-C mismatch. These findings highlight distinct maternal and fetal immunogenetic contributions to PE risk and underscore the importance of considering HLA diversity-rather than individual alleles alone-in studies of PE aetiology.

Humans↗
PubMed2025

Polygenic Risk Scores for Preeclampsia Prediction Beyond Gold-Standard Clinical Models in Multiethnic Populations.

BACKGROUND: Preeclampsia is a major cause of maternal and fetal mortality and morbidity. Early risk stratification enables timely preventative therapy in high-risk women. Polygenic risk scores (PGS) improve prediction in complex diseases, but their added value for preeclampsia remains unclear, particularly in comparison to gold-standard first-trimester prediction models and across non-European ancestries. METHODS: We evaluated the performance of both a preeclampsia and systolic blood pressure PGS in 2 prospective pregnancy cohorts with detailed phenotyping: the Fetal Medicine Foundation study (n=5207; 2127 cases) and the Pregnancy Outcome Prediction study (n=3659; 228 cases). Risk models included (1) clinical factors; (2) clinical factors plus PGS; (3) advanced model including first-trimester mean arterial pressure, PAPP-A (pregnancy-associated plasma protein-A), and uterine artery pulsatility index; and (4) advanced model plus PGS. Discriminative performance, measured by the area under the receiver operating characteristic curve, was assessed overall and by ancestry. RESULTS: The preeclampsia PGS was independently associated with preeclampsia (odds ratio per SD, 1.24 [95% CI, 1.17-1.31]; P<0.001). It modestly improved prediction over clinical models (area under the receiver operating characteristic curve 0.746 versus 0.750; P=0.017) but not over the advanced model (area under the receiver operating characteristic curve 0.817 versus 0.818; P=0.326). The systolic blood pressure PGS showed stronger performance, improving prediction over both models in women of European ancestry. No improvement was observed with either score in women of African ancestry. CONCLUSIONS: PGSs for preeclampsia and SBP provide modest added predictive value beyond clinical risk factors in European ancestry women. Limited utility in African ancestry women reflects underrepresentation in the genome-wide association studies used to develop current scores. As cohort sizes grow and models are refined, PGSs may become important tools for equitable risk stratification in maternal health.

Adult↗
PubMed2025

Methylome profiling of cell-free DNA during the early life course in (un)complicated pregnancies using MeD-seq: Protocol for a cohort study embedded in the prospective Rotterdam periconception cohort.

INTRODUCTION: Placental DNA methylation differences have been associated with timing in gestation and pregnancy complications. Maternal cell-free DNA (cfDNA) partly originates from the placenta and could enable the minimally invasive study of placental DNA methylation dynamics. We will for the first time longitudinally investigate cfDNA methylation during pregnancy by using Methylated DNA Sequencing (MeD-seq), which is compatible with low cfDNA levels and has an extensive genome-wide coverage. We aim to investigate DNA methylation in placental tissues and cfDNA during different trimesters in uncomplicated pregnancies, and in pregnancies with placental-related complications, including preeclampsia and fetal growth restriction. Identified gestational-age and disease-specific differentially methylated regions (DMRs) could lead to numerous applications including biomarker development. METHODS AND ANALYSIS: Our study design involves three sub-studies. Sub-study 1 is a single-centre prospective, observational subcohort embedded within the Rotterdam Periconception cohort (Predict study). We will longitudinally collect maternal plasma in each trimester and during delivery, and sample postpartum placentas (n = 300). In sub-study 2, we will prospectively collect first and second trimester placental tissues (n = 10 per trimester). In sub-study 3 we will retrospectively collect plasma after non-invasive prenatal testing (NIPT) in an independent validation case-control cohort (n = 30-60). A methylation-dependent restriction enzyme (LpnPI) will be used to generate DNA fragments followed by sequencing on the Illumina NextSeq2000 platform. DMRs will be identified in placental tissues and cell types, and in cfDNA related to gestational-age or placental-related complications. (Paired) placental methylation profiles will be correlated to DMRs in cfDNA to aid tissue-of-origin analysis. We will establish a methylation score to predict associated diseases. DISCUSSION: This study will provide insights in placental DNA methylation dynamics in health and disease, and could lead to clinical relevant biomarkers.

Humans↗
PubMed2026

MiR-26a-5p/EZH2 Mediates Wnt2 Promoter Methylation to Regulate Trophoblast Dysfunction.

INTRODUCTION: Preeclampsia (PE) is a common complication of pregnancy, with a concomitant incidence rate of up to 10% among pregnant women worldwide. METHODS: In the current research, we explored the role and mechanism of miR-26a-5p in trophoblast function using CCK-8, colony formation assay, and flow cytometry. The interaction between miR-26a-5p and EZH2 was analyzed using a luciferase reporter assay. Methylationspecific PCR was performed to detect the methylation level of Wnt2 in HTR8 cells. RESULTS: Wnt2 and miR-26a-5p promoted the proliferation and inhibited the apoptosis in trophoblasts (P<0.05). The secretion of inflammatory cytokines was suppressed by Wnt2 and miR-26a-5p (P<0.05). EZH2 was identified as a regulatory target of miR-26a-5p using HTR8 cells and bioinformatic tools. miR-26a-5p inhibited expression through direct binding to EZH2. Importantly, miR- 26a-5p mediated DNA methylation of Wnt2 to regulate Wnt2 expression in HTR8 cells. DISCUSSION: This study elucidates a novel regulatory axis that alleviates trophoblast dysfunction by promoting proliferation and suppressing inflammation and apoptosis. The findings reveal that the miR-26a-5p/EZH2/Wnt2 pathway, potentially involving promoter methylation, is crucial for maintaining trophoblast function. This work identifies a promising therapeutic target for PE, although further in vivo validation is required to confirm its clinical potential. CONCLUSION: It was found that miR-26a-5p increased the expression of Wnt2 by downregulating EZH2. Moreover, miR-26a-5p/EZH2/Wnt2 promoted the proliferation and inhibited the inflammation and apoptosis in trophoblasts. This research provides insight into the role of miR-26a- 5p/EZH2/Wnt2 as a novel indicator for the prevention and treatment of PE.

MicroRNAs↗
PubMed2026

Discovery and validation of GNA12circle as a first-trimester plasma eccDNA marker for early-onset preeclampsia.

BACKGROUND: Early-onset preeclampsia (EOPE) is a major cause of maternal and perinatal morbidity and is characterized by placental dysfunction, systemic endothelial injury, and hypertensive vascular stress. Because hypertensive disorders of pregnancy may also signal later maternal cardiovascular and cerebrovascular vulnerability, effective biomarkers for first-trimester risk assessment remain clinically important. Extrachromosomal circular DNA (eccDNA), a stable form of circulating cell-free DNA, has emerged as a potential source of disease-associated biomarkers. This study aimed to characterize first-trimester plasma eccDNA alterations associated with subsequent EOPE and to identify and validate a candidate circulating eccDNA marker for early risk assessment. METHODS: A two-stage nested case-control study was conducted within a prospective birth cohort. In the discovery stage, plasma samples collected at 11-13&#x202f;weeks of gestation from 5 women who subsequently developed EOPE and 5 matched normotensive controls were profiled by Circle-Seq to characterize genome-wide eccDNA alterations. Candidate eccDNAs were prioritized through differential abundance analysis and were further confirmed by outward PCR and Sanger sequencing. In the validation stage, the candidate selected marker was quantified by junction-specific qPCR in an independent cohort of 109 EOPE cases and 109 controls. Its potential predictive value was further evaluated alone and in combination with routine first-trimester clinical variables. RESULTS: In the exploratory discovery analysis, 410 nominally differentially abundant candidate eccDNAs were identified as a hypothesis-generating pool. Among these, GNA12circle (chr7:2876332-2,876,692) was prioritized and experimentally validated at the circular junction. In the independent validation cohort, plasma GNA12circle levels were significantly higher in women who later developed EOPE than in controls. When combined with routine first-trimester variables, GNA12circle improved predictive performance. The RF model showed the best overall cross-validated performance among the evaluated classifiers, with a mean held-out test-fold AUC of 0.843. CONCLUSION: First-trimester plasma eccDNA profiling revealed distinct alterations associated with subsequent EOPE, from which GNA12circle was identified and validated as a candidate circulating marker. These findings support further investigation of circulating eccDNA for early EOPE risk assessment in larger multicenter populations.

Humans↗
PubMed1976

[Glucose infusions in suspected chronic placental insufficiency caused by gestosis].

In this study glucose load and its possible therapeutical efficiency in chronic nutritive insufficiency of the placenta is investigated. Following a definite regime glucose infusions were applied to the mother prepartually as well as subpartually in order to substitute the carbohydrate metabolism of hypotrophic fetuses. Glucose values and the parameters of the acid-base-balance were taken and calculated. The microblood analyses were performed subpartually on the mother and the fetus and postpartually on the newborn. The results gained are discussed and explained with regard to metabolism. The glucose infusion therapy in the form mentioned is suited to influence favourably the fetal hypoglucosemia.

Blood Glucose↗