Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA197384 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disease, which can lead to adverse fetal outcomes, including preterm labor and intrauterine death. The pathogenesis of ICP is still unclear. We hypothesized that pathological index leads to abnormal placenta changes in ICP. Investigation of these differences in protein expression in parallel profiling is essential to understand the comprehensive pathophysiological mechanism underlying intrahepatic cholestasis of pregnancy(ICP)
2022-05-05 | PXD033701 |
Project description:Intrahepatic cholestasis of pregnancy (ICP) is strongly associated withan increased risk of adverse perinatal outcomes. Total bile acid (TBA) levels in the late second or third trimester are a major factor in the diagnosis. Here, we sought to establish the miRNA expression profile of plasma exosomes of ICP and identify possible biomarkers for the diagnosis of ICP.
2022-08-09 | GSE210764 | GEO
Project description:Short read whole genome sequencing (WGS) CRAM files for the NIHR BioResource Rare Diseases WGS project.Participants from the Intrahepatic Cholestasis of Pregnancy (ICP) Rare Disease domain
| EGAD00001004515 | EGA
Project description:Estrogens impair bile acid (BA) homeostasis, leading to intrahepatic cholestasis of pregnancy (ICP). ICP is characterized by elevated serum bilirubin and BAs, severe pruritus, and an increased risk of adverse perinatal outcomes. The constitutive androstane receptor (CAR) regulates genes involved in xenobiotic and BA detoxification. Previous studies suggest that CAR activation is protective in bile duct ligation–induced cholestasis and that major genes involved in BA elimination are downregulated in ethinylestradiol (EE)–induced cholestasis in mice. We examined whether CAR ligands could ameliorate cholestasis and prevent hepatic injury in an EE-induced cholestasis model using biochemical, transcriptomic, and BA metabolomic analyses. We found that estradiol inhibits and downregulates CAR target genes in vitro. Consistently, EE significantly suppresses hepatic CAR target gene expression in vivo, whereas the murine CAR agonist TCPOBOP partially restores the expression of selected detoxification genes, improves plasma alkaline phosphatase levels, and decreases hepatic BA accumulation. In humanized PXR–CAR–CYP3A mice with EE-induced cholestasis, MI763F, a novel and potent human CAR agonist, recapitulates the effects of TCPOBOP on key genes involved in BA metabolism and the BA metabolome, and significantly reduces hepatic BA accumulation. These results demonstrate that CAR ligands counteract EE-mediated disruption of genes involved in BA homeostasis.
2026-06-01 | GSE314547 | GEO
Project description:<p><strong>OBJECTIVE:</strong> Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of adverse pregnancy outcomes to the mother and fetus. As yet, the metabolic profiles and the association of the clinical features remain obscure.</p><p><strong>METHODS:</strong> Fifty seven healthy pregnant women and 52 patients with ICP were recruited in this study. Plasma samples were obtained from pregnancies who received prenatal care between the 30-36 weeks. Untargeted metabolomics to portray metabolic profiles were performed by LC/MS. Mul- combined with univariate data analysis and statistical analysis were performed to select differential metabolites between ICP and control group. Debiased sparse partial correlation (DSPC) network analysis of differential metabolites was performed to explore the potential mutual regulation among metabolites on the basis of de-sparsified graphical lasso modeling procedure. Pathway analysis was performed using MetaboAnalyst. Linear regression and Pearson correlation analysis were applied to analyze correlations associated with bile acid levels, metabolites, newborn weight and pregnancy outcome in ICP patients.</p><p><strong>RESULTS:</strong> Conspicuous metabolic changes and choreographed metabolic profiles were disclosed: 125 annotated metabolites and eighteen metabolic pathways were disturbed in ICP patients. DSPC networks indicated dense interactions among amino acids and their derivatives, bile acids, carbohydrates and organic acids. The levels of total bile acid were increased in ICP patients with meconium-stained amniotic fluid compared with those without MSAF. Abnormal tryptophan metabolism, elevated long chain saturated fatty acid and estrone sulfate levels, and low antioxidant capacity were relevant to increasing bile acid levels. Correlation analysis showed that newborn body weights were significant correlated with the levels of several bile acids and some metabolites of amino acids.</p><p><strong>CONCLUSION:</strong> The ICP patient showed metabolic disorder, and the levels of a number of metabolites were correlated with TBA levels and neonatal body weights. These results provide us important information to further understand the metabolic characteristics of patients with ICP and adverse pregnancy outcomes.</p>
2022-03-01 | MTBLS2627 | MetaboLights
Project description:Intrahepatic cholestasis of pregnancy (ICP) is estimated to impact between 0.4% and 5% of pregnancies worldwide. This disease is associated with elevated maternal bile acids and frequently untoward neonatal outcomes such as respiratory distress and asphyxia. Multiple candidate genes have been implicated, but none have provided insight into the mechanisms of neonatal respiratory distress and death. Herein our studies demonstrate that maternal cholestasis (due to Abcb11 deficiency) produces 100% neonatal death within 24h due to atelectasis producing pulmonary hypoxia, which recapitulates the respiratory distress and asphyxia of human ICP. We show that these neonates have elevated pulmonary bile acids that are associated with disrupted structure of pulmonary surfactant. Maternal absence of Nr1i2 superimposed upon Abcb11 deficiency strongly increased neonatal survival and is directly related to reduced maternal bile acid concentrations. The mechanism accounting for reduced serum bile acids in the mothers deficient in both Nr1i2 and Abcb11 appears related to disrupted reabsorption of intestinal bile acids due to changes in transporter expression. These findings provide novel insights into pulmonary failure by revealing bile acids capability to disrupt the structure of surfactant producing collapsed alveoli, pulmonary failure and ultimately death. These findings have important implications for neonatal health especially when maternal bile acids are elevated during pregnancy and highlight a potential pathway and targets amenable to therapeutic intervention to ameliorate this condition. We used microarrays to measure changes in gene expression profiles in lung tissues from Abcb11+/- lungs after interbreeding C57BL/6 wild-type female or C57BL/6 Abcb11-/- female mice against either C57BL/6 wild-type male mice or C57BL/6 Abcb11-/- male mice to create only heterozygote offspring. We also measured profiles in liver tissues from age-matched C57BL/6 wild-type and C57BL/6 Abcb11-/- mice. Lung tissues were collected from day E17.5, E18.5 and neonatal (N0) mice. Liver tissues were collected from 1.5-month-old C57BL/6 wildtype and Abcb11-/- mice.
2015-09-23 | E-GEOD-70179 | biostudies-arrayexpress
Project description:Intrahepatic cholestasis of pregnancy (ICP) is estimated to impact between 0.4% and 5% of pregnancies worldwide. This disease is associated with elevated maternal bile acids and frequently untoward neonatal outcomes such as respiratory distress and asphyxia. Multiple candidate genes have been implicated, but none have provided insight into the mechanisms of neonatal respiratory distress and death. Herein our studies demonstrate that maternal cholestasis (due to Abcb11 deficiency) produces 100% neonatal death within 24h due to atelectasis producing pulmonary hypoxia, which recapitulates the respiratory distress and asphyxia of human ICP. We show that these neonates have elevated pulmonary bile acids that are associated with disrupted structure of pulmonary surfactant. Maternal absence of Nr1i2 superimposed upon Abcb11 deficiency strongly increased neonatal survival and is directly related to reduced maternal bile acid concentrations. The mechanism accounting for reduced serum bile acids in the mothers deficient in both Nr1i2 and Abcb11 appears related to disrupted reabsorption of intestinal bile acids due to changes in transporter expression. These findings provide novel insights into pulmonary failure by revealing bile acids capability to disrupt the structure of surfactant producing collapsed alveoli, pulmonary failure and ultimately death. These findings have important implications for neonatal health especially when maternal bile acids are elevated during pregnancy and highlight a potential pathway and targets amenable to therapeutic intervention to ameliorate this condition.
2015-09-23 | GSE70179 | GEO
Project description:Peptidomics Landscape of Intrahepatic Cholestasis of Pregnancy in vitro
2025-03-20 | PXD062070 |
Project description:Unique microRNA expression profiles in plasmic exosomes from intrahepatic cholestasis of pregnancy
| PRJNA867388 | ENA