Maternal plasma cell-free RNA sequencing for preeclamptic and normotensive mothers
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE192902 | GEO | 2022/01/03
REPOSITORIES: GEO
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Project description:Small RNA sequencing on trophoblast debris samples was employed to profile the small RNA contents in either normotensive or preeclamptic trophoblast debris. We have identified 1278 miRNAs and 2646 non-miRNA small RNA fragments across all trophoblast debris samples. Differential expression analysis was executed by iSRAP small RNA sequencing analysis pipeline and we identified 16 miRNAs, 5 tRNA fragments from 3 different tRNAs, 13 snRNA fragments and 85 rRNA fragments differentially contained between preeclamptic and normotensive trophoblast debris
2017-11-22 | GSE85926 | GEO
Project description:BackgroundEpoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE) are cytochrome P450 metabolites of arachidonic acid posited to act in the circulatory adaptation to pregnancy and the development of preeclampsia. Red blood cells (RBCs) may function as major contributors of cis- and trans-EETs.MethodsWe performed paired analyses of EETs, dihydroxyeicosatrienoic acids (DHETs), and 20-HETE in RBCs, plasma, and urine from preeclamptic and normotensive pregnant and nonpregnant women. Blood from fetal and maternal circulation was collected. EETs, DHETs, and 20-HETE were analyzed by gas chromatography and liquid chromatography mass spectrometry. Vascular function and inflammation indices were analyzed.ResultsPlasma EET is higher in normotensive (median, range; 9.9, 6.3-25.2ng/mL n = 29) and preeclamptic (10.9, 6.0-48.0ng/mL, n = 19) women than in nonpregnant controls (7.3, 3.7-10.2ng/mL, n = 19) and correlate with RBC EETs, C-reactive protein, and arterial stiffness. Renal production of EETs, measured as urinary DHETs, was reduced in preeclamptic (4.5, 1.6-24.5ng/mg creatinine) compared to normotensive (11.4, 1.6-44.5ng/mg creatinine) pregnancies. EETs are 3- to 5-fold greater in fetoplacental than in maternal circulation (RBCs 36.6, 13.1-69.4 vs. 12.5, 6.4-12.0ng/10(9) cells; plasma 31.6, 8.5-192.6 vs. 12.0, 6.8-48.0ng/mL). Both cis- and trans-EETs are present in fetal RBCs.ConclusionsRBCs contribute to elevated levels of EETs in the fetoplacental circulation. EETs may modulate systemic and fetoplacental hemodynamics in normal and preeclamptic pregnancies. Decreased renal EET generation may be associated with the development of maternal renal dysfunction and hypertension in preeclampsia.
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Project description:Preeclampsia, an important cause of maternal and fetal morbidity and mortality, is associated with increased sFLT1 levels and with structural and functional damage to the glycocalyx contributing to endothelial dysfunction. We investigated glycocalyx components in relation to preeclampsia in human samples. While soluble syndecan-1 and heparan sulphate were similar in plasma of preeclamptic and normotensive pregnant women, dermatan sulphate was increased and keratan sulphate decreased in preeclamptic women. Dermatan sulphate was correlated with soluble syndecan-1, and inversely correlated with blood pressure and activated partial thromboplastin time. To determine if syndecan-1 was a prerequisite for the sFlt1 induced increase in blood pressure in mice we studied the effect of sFlt1 on blood pressure and vascular contractile responses in syndecan-1 deficient and wild type male mice. The classical sFlt1 induced rise in blood pressure was absent in syndecan-1 deficient mice indicating that syndecan-1 is a prerequisite for sFlt1 induced increase in blood pressure central to preeclampsia. The results show that an interplay between syndecan-1 and dermatan sulphate contributes to sFlt1 induced blood pressure elevation in pre-eclampsia.
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Project description:We sequenced cell-free RNA (cfRNA) for five cancer types (colorectal cancer, stomach cancer, liver cancer, lung cancer and esophageal cancer) and healthy individuals in 230 plasma samples collected from 6 clinical centers in China. Cancer related signaling pathway and microbial genus were identified. Cancer detection and specific classification were achieved through combining both host and microbial cfRNA reads.
2022-07-12 | GSE174302 | GEO
Project description:Nitric oxide (NO) plays a key role in placental biology, and placental dysfunction is the main pathogenesis pathway for preeclampsia, yet the direct placental targets of NO actions have not been determined. Covalent adduction of an NO moiety to cysteines, termed S-nitrosylation (SNO), is emerging as a key route by which NO can directly modulate protein functions. This study was conducted to analyze global S-nitroso (SNO)-proteins in human placentas and to determine if their levels differ in normotensive versus severe preeclamptic placentas. Although total nitrite/nitrate increased, total levels of SNO-proteins and nitrosylated forms of endothelial NO synthase and heat shock protein 90 were decreased by preeclampsia. We further compared normotensive and preeclamptic placental nitroso-proteomes (total SNO-protein profiles) by using a biotin and CyDye switch test combined with two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) and identified SNO-proteins by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Numerous SNO-proteins were displayed as spots on 2D-DIGE gels. One hundred spots of interest were excised; 46 spots were identified, of which 8 spots were novel SNO-proteins; levels of 15 spots were increased, and 6 spots were decreased, and the rest were unchanged by preeclampsia. Pathway analysis suggested that placental SNO-proteins are involved in regulating various cellular functions including protein synthesis, cell movement and metabolism, cell signaling, and other functions. These data therefore show for the first time that SNO is a crucial mechanism by which NO directly regulates placental proteins linked to various biological pathways. The significantly altered placental nitroso-proteome in preeclampsia suggests that SNO plays a role in the placental pathophysiology in preeclampsia.
| S-EPMC3080422 | biostudies-literature
Project description:BackgroundWhile preeclampsia (PE) is a leading cause of pregnancy-related morbidity/mortality, its underlying mechanisms are not fully understood. DNA methylation (DNAm) is a dynamic regulator of gene expression that may offer insight into PE pathophysiology and/or serve as a biomarker (e.g., risk, subtype, a therapeutic response). This study's purpose was to evaluate for differences in blood-based DNAm across all trimesters between individuals eventually diagnosed with PE (cases) and individuals who remained normotensive throughout pregnancy, did not develop proteinuria, and birthed a normally grown infant (controls).ResultsIn the discovery phase, longitudinal, genome-wide DNAm data were generated across three trimesters of pregnancy in 56 participants (n=28 cases, n=28 controls) individually matched on self-identified race, pre-pregnancy body mass index, smoking, and gestational age at sample collection. An epigenome-wide association study (EWAS) was conducted, using surrogate variable analysis to account for unwanted sources of variation. No CpGs met the genome-wide significance p value threshold of 9×10-8, but 16 CpGs (trimester 1: 5; trimester 2: 1; trimester 3: 10) met the suggestive significance threshold of 1×10-5. DNAm data were also evaluated for differentially methylated regions (DMRs) by PE status. Three DMRs in each trimester were significant after Bonferonni-adjustment. Since only third-trimester samples were available from an independent replication sample (n=64 cases, n=50 controls), the top suggestive hits from trimester 3 (cg16155413 and cg21882990 associated with TRAF3IP2-AS1/TRAF3IP2 genes, which also made up the top DMR) were carried forward for replication. During replication, DNAm data were also generated for validation purposes from discovery phase third trimester samples. While significant associations between DNAm and PE status were observed at both sites in the validation sample, no associations between DNAm and PE status were observed in the independent replication sample.ConclusionsThe discovery phase findings for cg16155413/cg21882990 (TRAF3IP2-AS1/TRAF3IP2) were validated with a new platform but were not replicated in an independent sample. Given the differences in participant characteristics between the discovery and replication samples, we cannot rule out important signals for these CpGs. Additional research is warranted for cg16155413/cg21882990, as well as top hits in trimesters 1-2 and significant DMRs that were not examined in the replication phase.
| S-EPMC10101051 | biostudies-literature
Project description:We compared patterns of blood pressure (BP) change among normotensive women, women who developed gestational hypertension or preeclampsia, and women who had essential hypertension to examine how distinct these conditions are and whether rates of BP change may help to identify women at risk for hypertensive disorders. We used antenatal clinic BP measurements (median, 14 per woman) of 13016 women from the Avon Longitudinal Study of Parents and Children who had a singleton or twin live birth surviving until ? 1 year. Linear spline models were used to describe changes in systolic and diastolic BPs in different periods of pregnancy (8-18, 18-30, 30-36, and ? 36 weeks' gestation). Women who had essential hypertension and those who developed gestational hypertension or preeclampsia had higher BP at 8 weeks' gestation (baseline) compared with normotensive women. The decrease in BP until 18 weeks was smaller in gestational hypertensive compared with normotensive pregnancies. BP rose more rapidly from 18 weeks onward in gestational hypertensive and preeclamptic pregnancies and from 30 weeks onward in essential hypertensive compared with normotensive pregnancies. Women who developed preeclampsia had a more rapid increase in BP from 30 weeks onward than those who developed gestational hypertension or had essential hypertension. Our findings indicate notable patterns of BP change that distinguish women with essential hypertension, gestational hypertension, and preeclampsia from each other and from normotensive women, even from early pregnancy. These distinct patterns may be useful for identifying women at risk of developing a hypertensive disorder later in pregnancy.
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Project description:We sequenced cell-free nucleaic acid (cfNA) for 2 major cancer types (44 samples of colorectal cancer and 36 samples of stomach cancer) and 81 samples of healthy individuals collected in China. Cancer related signaling pathway were identified. Cancer detection and specific classification were achieved through combining both cfRNA and cfDNA reads.
2023-09-28 | GSE186587 | GEO
Project description:We sequenced cell-free nucleaic acid (cfNA) for 2 major cancer types (44 samples of colorectal cancer and 36 samples of stomach cancer) and 81 samples of healthy individuals collected in China. Cancer related signaling pathway were identified. Cancer detection and specific classification were achieved through combining both cfRNA and cfDNA reads.
2023-09-28 | GSE186575 | GEO
Project description:We sequenced cell-free nucleaic acid (cfNA) for 2 major cancer types (44 samples of colorectal cancer and 36 samples of stomach cancer) and 81 samples of healthy individuals collected in China. Cancer related signaling pathway were identified. Cancer detection and specific classification were achieved through combining both cfRNA and cfDNA reads.
2023-09-28 | GSE186573 | GEO