Cell free expression of hif1α and p21 in maternal peripheral blood as a marker for preeclampsia and fetal growth restriction.
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ABSTRACT:
SUBMITTER: Ashur-Fabian O
PROVIDER: S-EPMC3353943 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectivesPreeclampsia and fetal growth restriction are obstetrical syndromes associated with abnormal placental implantation and changes in the activation status of maternal leukocytes. This study is aimed to determine by a simple, rapid fluorescent assay the changes in maternal serum total cell-free DNA (t-cfDNA) concentrations in women with preeclampsia and those with fetal growth restriction (FGR).Study designA cross-sectional study was conducted measuring maternal serum t-cfDNA concentrations. Women were classified into the following groups: 1) patients with preeclampsia (n = 21); 2) FGR-estimated fetal weight below the 10thpercentile (n = 28); and 3) normal pregnancy (n = 39). Serum samples were directly assayed for t-cfDNA using a rapid fluorescent SYBR Gold assay. Elevated maternal serum t-cfDNA concentrations were defined as a cutoff>850ng/ml. Nonparametric statistics were used for analysis.ResultsWomen with preeclampsia had a higher median maternal serum concentration (802 ng/ml, 400-2272 ng/ml) than women with a normal pregnancy (499 ng/ml, 0-1892 ng/ml, p = 0.004) and those with FGR (484 ng/ml, 72-2187 ng/ml, p = 0.012). Moreover, even patients with FGR <5th percentile and abnormal Doppler had a lower median maternal serum t-cfDNA than those with preeclampsia (median 487 ng/ml, 144-1971 ng/ml, p = 0.022). The median concentration of t-cfDNA did not differ between women with a normal pregnancy and those with FGR (p = 0.54), as well as those with fetuses <5th percentile and abnormal Doppler (p = 0.7). Women with preeclampsia had a higher proportion of elevated t-cfDNA than those with a normal pregnancy (p = 0.015) and patients with FGR (p = 0.025).ConclusionsPreeclampsia is associated with higher maternal serum t-cfDNA concentration than normal pregnancy or FGR. This observation may reflect an increased systemic activation of the maternal inflammation, rather than placental; this assumption is supported by the fact that we did not observe a significant change in the maternal serum t-cfDNA in patients with placental-mediated FGR.
| S-EPMC6042756 | biostudies-literature
Project description:Preeclampsia (PE) and fetal growth restriction (FGR) are both placenta-mediated disorders with unclear pathogenesis. Metabolomics of maternal and fetal pairs might help in understanding these disorders. We recruited prospectively pregnancies with normotensive FGR, PE without FGR, PE + FGR and uncomplicated pregnancies as controls. Nuclear magnetic resonance metabolomics were applied on plasma samples collected at delivery. Advanced lipoprotein, glycoprotein and choline profiling was performed using the Liposcale test. The software package Dolphin was used to quantify 24 low-molecular-weight metabolites. Statistical analysis comprised the comparison between each group of complicated pregnancies versus controls, considering 5% false discovery rate correction. Lipid profiles were altered in accordance with the clinical presentation of these disorders. Specifically, PE mothers and FGR fetuses (with or without FGR or PE, respectively) exhibited a pro-atherogenic and pro-inflammatory profile, with higher concentrations of triglycerides, remnant cholesterol (VLDL, IDL) and Glc/GalNAc-linked and lipid-associated glycoproteins compared to controls. Low-molecular-weight metabolites were extensively disturbed in preeclamptic mothers, with or without FGR. Growth restricted fetuses in the presence of PE showed changes in low-molecular-weight metabolites similar to their mothers (increased creatine and creatinine), while normotensive FGR fetuses presented scarce differences, consistent with undernutrition (lower isoleucine). Further research is warranted to clarify maternal and fetal adaptations to PE and FGR.
| S-EPMC8277896 | biostudies-literature
Project description:ObjectiveTo assess the maternal blood levels of fatty acids (FAs) in pregnancies with fetal growth restriction (FGR).MethodsThis prospective cross-sectional study included pregnant women with gestational age between 26 and 37 + 6 weeks with FGR and appropriate for gestational age (AGA) fetuses. The levels of saturated, trans, monounsaturated, and polyunsaturated FAs were measured using centrifugation and liquid chromatography. The Student's t-test, Mann-Whitney test, and general linear model, with gestational age and maternal weight as covariants, were used to compare FA levels and the FGR and AGA groups. The Chi-square was used to evaluate the association between groups and studied variables.ResultsMaternal blood sample was collected from 64 pregnant women, being 24 FGR and 40 AGA. A weak positive correlation was found between the palmitoleic acid level and maternal weight (r = 0.285, p = 0.036). A weak negative correlation was found between the gamma-linoleic acid level and gestational age (r = - 0.277, p = 0.026). The median of the elaidic acid level (2.3 vs. 4.7 ng/ml, p = 0.045) and gamma-linoleic acid (6.3 vs. 6.6 ng/ml, p = 0.024) was significantly lower in the FGR than the AGA group. The palmitoleic acid level was significantly higher in the FGR than AGA group (50.5 vs. 47.6 ng/ml, p = 0.033).ConclusionPregnant women with FGR had lower elaidic acid and gamma-linoleic acid levels and higher palmitoleic acid levels than AGA fetuses.
| S-EPMC10139773 | biostudies-literature
Project description:We investigated associations of early pregnancy maternal peripheral blood gene expression with preeclampsia. In a nested case control study, gene expression of peripheral blood, collected at 16weeks of gestation on average from 16 women destined to develop preeclampsia and 16 women who had normotensive pregnancies was profiled using Affymetrix GeneChip Arrays. Fold change and Student's T-test analyses were used to compare differential gene expression across the groups. Functions and functional relationships as well as common regulatory sequences of differentially expressed genes were investigated. Genes participating in abnormal placentation (e.g COL1A1), immune/inflammation response (e.g. IKBKB) and cellular development (including cell cycle) (e.g. RBI) were differentially expressed in early pregnancy peripheral blood in preeclampsia. We identified transcription factors (i.e. Sp1, MAZ and MZF1) that may account for co-expression of differentially expressed genes. Preeclampsia is associated with differential gene expression in early pregnancy peripheral blood.
| S-EPMC3077242 | biostudies-literature
Project description:To explore the use of maternal urine proteome for the identification of preeclampsia biomarkers. Maternal urine samples from women with and without preeclampsia were used for protein discovery followed by a validation study. The targeted proteins of interest were then measured in urine samples collected at 20-24 and 30-34 weeks among nine women who developed preeclampsia, one woman with fetal growth restriction, and 20 women with uncomplicated pregnancies from a longitudinal study. Protein identification and quantification was obtained using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Among the 1108 urine proteins quantified in the discovery study, 21 were upregulated in preeclampsia and selected for validation. Nineteen (90%) proteins were confirmed as upregulated in preeclampsia cases. Among them, two proteins, ceruloplasmin and serpin A7, were upregulated at 20-24 weeks and 30-34 weeks of gestation (p < 0.05) in cases of preeclampsia, and could have served to identify 60% of women who subsequently developed preeclampsia and/or fetal growth restriction at 20-24 weeks of gestation, and 78% at 30-34 weeks, for a false-positive rate of 10%. Proteomic profiling of maternal urine can differentiate women with and without preeclampsia. Several proteins including ceruloplasmin and serpin A7 are upregulated in maternal urine before the diagnosis of preeclampsia and potentially fetal growth restriction.
| S-EPMC8537852 | biostudies-literature
Project description:ImportanceIt remains unknown whether neurodevelopmental impairments are directly associated with the structural development of the brain in offspring with fetal growth restriction (FGR) and mothers with preeclampsia (PE) or gestational hypertension (GH).ObjectivesTo assess whether fetal corpus callosum (CC) development differed among pregnancies with PE or GH with FGR, pregnancies with PE or GH without FGR, and normotensive pregnancies, particularly the severity of maternal disease and FGR, and to identify the association between adverse perinatal outcomes and structural development of the CC in fetuses with FGR in pregnancies with PE or GH.Design, setting, and participantsThis retrospective matched case-control study was conducted between January 1, 2014, and January 31, 2021, at Women's Hospital, Zhejiang University School of Medicine in Hangzhou, China. The participant group included cases of singleton pregnancies with PE or GH with FGR; the control groups included cases with PG or GH without FGR and cases with paired normotensive pregnancy.ExposuresMaternal PE or GH and FGR.Main outcomes and measuresThe length, thickness, total area, subdivision areas, and apparent diffusion coefficient (ADC) values of fetal CC were measured on magnetic resonance imaging (MRI) and analyzed. The association between adverse perinatal outcomes and structural development of CC was further investigated.ResultsA total of 56 pregnant individuals with singleton pregnancies and PE or GH and fetuses with FGR were enrolled (maternal median [IQR] age, 29.0 [26.0-34.0] years; mean [SD] gestational age at MRI, 33.6 [2.5] weeks). Significant patterns of decreased median (IQR) fetal CC length (0.4284 [0.4079-0.4470] mm vs 0.4614 [0.4461-0.4944] mm, P < .001, vs 0.4591 [0.4310-0.4927] mm, P < .001) and mean (SD) CC total area (1.0779 [0.1931] mm2 vs 1.1896 [0.1803] mm2, P = .001, vs 1.1438 [0.1935] mm2, P = .02), adjusted for the cephalic index, was observed in cases of PE or GH with FGR compared with cases without FGR and cases with normotensive pregnancy. The splenium region of fetal CC also exhibited the distinct alterations in macrostructural development (with FGR: 0.3149 [0.0697] mm2 vs without FGR: 0.3727 [0.0698] mm2, P < .001, vs normotensive pregnancies: 0.3565 [0.0763] mm2, P < .001) and microstructural development (median [IQR] ADC values: 1.47 [1.38-1.57] × 10-3 mm2/s vs 1.57 [1.53-1.63] × 10-3 mm2/s, P = .009, vs 1.63 [1.50-1.70] × 10-3 mm2/s, P < .001) in all groups. Furthermore, significant associations were found between structural abnormality of the splenium region and adverse perinatal outcomes in the PE or GH with FGR group (mean [SD] ADC value: 1.40 [0.07] × 10-3 mm2/s; P = .04).Conclusions and relevanceResults of this study suggest that, in fetuses with FGR in pregnancies with PE or GH, decreased structural development of the CC, predominantly the splenium region, may be significantly associated with a higher risk of adverse perinatal outcomes and may be regarded as an MRI-based biomarker for better prenatal counseling and early management decisions.
| S-EPMC9379741 | biostudies-literature
Project description:Preeclampsia and fetal growth restriction (FGR) are major causes of the more than 5 million perinatal and infant deaths occurring globally each year, and both are associated with placental dysfunction. The risk of perinatal and infant death is greater in males, but the mechanisms are unclear. We studied data and biological samples from the Pregnancy Outcome Prediction (POP) study, a prospective cohort study that followed 4,212 women having first pregnancies from their dating ultrasound scan through delivery. We tested the hypothesis that fetal sex would be associated with altered placental function using multiomic and targeted analyses. We found that spermine synthase (SMS) escapes X-chromosome inactivation (XCI) in the placenta and is expressed at lower levels in male primary trophoblast cells, and male cells were more sensitive to polyamine depletion. The spermine metabolite N1,N12-diacetylspermine (DiAcSpm) was higher in the female placenta and in the serum of women pregnant with a female fetus. Higher maternal serum levels of DiAcSpm increased the risk of preeclampsia but decreased the risk of FGR. To our knowledge, DiAcSpm is the first maternal biomarker to demonstrate opposite associations with preeclampsia and FGR, and this is the first evidence to implicate polyamine metabolism in sex-related differences in placentally related complications of human pregnancy.
| S-EPMC6124516 | biostudies-literature
Project description:A universal method confirming the presence of circulating cell-free fetal (ccff) DNA in maternal plasma is important in the field of noninvasive prenatal diagnostics. Restriction endonuclease digestion of one allele of a single-nucleotide polymorphism (SNP) was used to allow detection of paternal alleles in maternal plasma DNA. Multiplexed genotyping of 92 panethnic high-frequency SNPs predicted >0.99 probability of detecting at least four informative loci per sample. Child-maternal paired DNA samples were used to confirm detection of 2% child's heterozygous DNA in a background of maternal DNA homozygous for the digestible allele. By restriction endonuclease digestion of DNA in a PCR cocktail before thermal cycling, 10 genomic copies of a paternal SNP allele were detectable in a background of 990 maternal SNP alleles. A comparison of 154 pregnant and nonpregnant female plasma DNA samples demonstrated enhanced detection of nondigestible SNP alleles in maternal plasma. Receiver operating characteristic curve analysis showed an optimal detection threshold of four nondigestible SNP alleles in plasma for the confirmation of ccff DNA and 98% sensitivity and 96% specificity at a 95% confidence level. Our study demonstrates the ability of this technique to confirm the presence of paternal alleles from ccff DNA in maternal plasma.
| S-EPMC3123783 | biostudies-literature
Project description:UnlabelledPreeclampsia is a major obstetrical complication affecting maternal and fetal health. While it is clear that there is a substantial placental contribution to preeclampsia pathogenesis, the maternal contribution is less well characterized. We therefore performed a genome-wide transcriptome analysis to explore disease-associated changes in maternal gene expression patterns in peripheral blood mononuclear cells (PBMCs).MethodsPreeclampsia was defined as gestational hypertension, proteinuria and hyperurecimia. Total RNA was isolated from PBMCs obtained from women with uncomplicated pregnancies (n = 5) and women with preeclamptic pregnancies (n = 5). Gene expression analysis was carried out using Agilent oligonucleotide microarrays. Biological pathway analysis was undertaken using Ingenuity Pathway Analysis software. Quantitative real-time PCR (QRTPCR) was performed to validate the gene expression changes of selected genes in normotensive and preeclamptic patients (n = 12 each).ResultsWe identified a total of 368 genes that were differentially expressed in women with preeclampsia compared to normal controls with false discovery rate (FDR) controlled at 10%. In follow up experiments we further analyzed the expression levels of a number of genes that were identified as altered by the microarray data including survivin (BIRC5), caveolin (CAV1), GATA binding protein-1 (GATA1), signal tranducer and activator of transcription 1 (STAT1), E2F transcription factor-1 (E2F1), fibronectin-1 (FN1), interleukin-4 (IL-4), matrix metalloprotease-9 (MMP-9) and WAP four disulfide domain protein (WFDC-1) by QRTPCR. Additionally we performed immuno blot analysis and zymography to verify some of these candidate genes at the protein level. Computational analysis of gene function identified an anti-proliferative and altered immune function cellular phenotype in severe preeclamptic samples.ConclusionsWe have characterized the genome-wide mRNA expression changes associated with preeclampsia-specific genes in circulating maternal blood cells at the time of delivery. In addition to providing information relating to the biological basis of the preeclampsia phenotype, our data provide a number of potential biomarkers for use in the further characterization of this disease.
| S-EPMC3040985 | biostudies-literature
Project description:ObjectiveTo examine whether maternal race could affect the relationship between fetal sex and preeclampsia.Material and methodsThis study was a cohort analysis using prospectively collected data from pregnant women who participated in the Vitamin Antenatal Asthma Reduction Trial (VDAART). Preeclampsia was the secondary outcome of VDAART. We examined the association of fetal sex with preeclampsia and its potential interaction with maternal race in 813 pregnant women (8% with preeclampsia) in logistic regression models with adjustment for preterm birth (<37 weeks of gestation), maternal age, education, and body mass index at enrollment and clinical center. We further conducted a race stratified analysis and also examined whether any observed association was dependent on the gestational age at delivery and prematurity.ResultsIn an analysis of all races combined, preeclampsia was not more common among pregnant women with a male fetus compared to those with a female fetus (odds ratio [OR] = 1.3, 95% CI = 0.81, 2.24). There was an interaction between African American race and fetal sex in association with preeclampsia after adjustment for preterm delivery and other potential confounders (p = .014). In race stratified analyses, we observed higher odds of preeclampsia among African American pregnant women who carried male fetuses after adjustment for preterm delivery and other potential confounders (adjusted OR = 2.4, 95% CI = 1.12, 5.60).ConclusionWe observed fetal sexual dimorphic differences in the occurrence of preeclampsia in African American women, but not in Whites. Information on fetal sex may ultimately improve the prediction of pre-eclampsia in African American mothers, who might be at higher risk for this adverse condition in pregnancy.
| S-EPMC7954987 | biostudies-literature