Transcription profiling of human newborn cord blood born to arsenic exposed mothers reveals activation of inflammation/NF-kappaB signalling
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Rebecca Fry
PROVIDER: E-GEOD-7967 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
Activation of inflammation/NF-kappaB signaling in infants born to arsenic-exposed mothers.
Fry Rebecca C RC Navasumrit Panida P Valiathan Chandni C Svensson J Peter JP Hogan Bradley J BJ Luo Manlin M Bhattacharya Sanchita S Kandjanapa Krittinee K Soontararuks Sumitra S Nookabkaew Sumontha S Mahidol Chulabhorn C Ruchirawat Mathuros M Samson Leona D LD
PLoS genetics 20071101 11
The long-term health outcome of prenatal exposure to arsenic has been associated with increased mortality in human populations. In this study, the extent to which maternal arsenic exposure impacts gene expression in the newborn was addressed. We monitored gene expression profiles in a population of newborns whose mothers experienced varying levels of arsenic exposure during pregnancy. Through the application of machine learning-based two-class prediction algorithms, we identified expression sign ...[more]
Similar Datasets
Project description:We are investigating the transcriptional response of newborns in response to prenatal arsenic exposure We used microarrays to detail the global programme of gene expression response due to prenatal arsenic exposure Keywords: dose (arsenic)
2007-11-01 | GSE7967 | GEO
Project description:The Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gómez Palacio, Mexico was recently established to better understand the impacts of prenatal exposure to inorganic arsenic (iAs). In this study, we examined a subset (n = 40) of newborn cord blood samples for microRNA (miRNA) expression changes associated with in utero arsenic exposure. Levels of iAs in maternal drinking water (DW-iAs) and maternal urine were assessed. Levels of DW-iAs ranged from below detectable values to 236 µg/L (mean = 51.7 µg/L). Total arsenic in maternal urine (U-tAs) was defined as the sum of iAs and its monomethylated and dimethylated metabolites (MMAs and DMAs, respectively) and ranged from 6.2 to 319.7 µg/L (mean = 64.5 µg/L). Genome-wide miRNA expression analysis of cord blood revealed 12 miRNAs with increasing expression associated with U-tAs. Transcriptional targets of the miRNAs were computationally predicted and subsequently assessed using transcriptional profiling. Pathway analysis demonstrated that the U-tAs-associated miRNAs are involved in signaling pathways related to known health outcomes of iAs exposure including cancer and diabetes mellitus. Immune response-related mRNAs were also identified with decreased expression levels associated with U-tAs, and predicted to be mediated in part by the arsenic-responsive miRNAs. Results of this study highlight miRNAs as novel responders to prenatal arsenic exposure that may contribute to associated immune response perturbations. We assessed the impact of prenatal exposure to arsenic on genome-wide miRNA expression profiles and their potential influence on gene expression patterns in the Biomarkers of Exposure to ARsenic (BEAR) prospective pregnancy cohort. This cohort includes residents from Gómez Palacio, located in the state of Durango in the Lagunera region of Northern Mexico. A total of 200 pregnant women residing in Gómez Palacio, State of Durango, Mexico, were recruited at the General Hospital of Gómez Palacio to participate in the BEAR prospective pregnancy cohort. The present study focuses on miRNA expression profiles and utilizes 40 samples obtained from mother-newborn pairs selected from the larger cohort (n=200). The subcohort was selected to include subjects exposed to varying levels of arsenic as determined by both total arsenic in maternal urine (U-tAs) and inorganic arsenic in drinking water (DW-iAs). Cord blood samples were collected from the newborns immediately after infant delivery. Blood samples were collected using PreAnalytix PaxGene RNA tubes and extracted using the PAXgene RNA Kit, per standard protocol (Qiagen, Valencia, CA). Isolated RNA used for microarray analysis were amplified and labeled using the NuGEN Ovation Pico WTA System V2 and Encore Biotin Module, respectively (NuGEN, San Carlos, CA). RNA isolated from 40 cord blood samples were labeled and hybridized to the Agilent Human miRNA Microarray, based off miRBase v16.0.
2014-01-22 | E-GEOD-48353 | biostudies-arrayexpress
Project description:The Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gómez Palacio, Mexico was recently established to better understand the impacts of prenatal exposure to inorganic arsenic (iAs). In this study, we examined a subset (n = 40) of newborn cord blood samples for microRNA (miRNA) expression changes associated with in utero arsenic exposure. Levels of iAs in maternal drinking water (DW-iAs) and maternal urine were assessed. Levels of DW-iAs ranged from below detectable values to 236 µg/L (mean = 51.7 µg/L). Total arsenic in maternal urine (U-tAs) was defined as the sum of iAs and its monomethylated and dimethylated metabolites (MMAs and DMAs, respectively) and ranged from 6.2 to 319.7 µg/L (mean = 64.5 µg/L). Genome-wide miRNA expression analysis of cord blood revealed 12 miRNAs with increasing expression associated with U-tAs. Transcriptional targets of the miRNAs were computationally predicted and subsequently assessed using transcriptional profiling. Pathway analysis demonstrated that the U-tAs-associated miRNAs are involved in signaling pathways related to known health outcomes of iAs exposure including cancer and diabetes mellitus. Immune response-related mRNAs were also identified with decreased expression levels associated with U-tAs, and predicted to be mediated in part by the arsenic-responsive miRNAs. Results of this study highlight miRNAs as novel responders to prenatal arsenic exposure that may contribute to associated immune response perturbations. We assessed the impact of prenatal exposure to arsenic on genome-wide miRNA expression profiles and their potential influence on gene expression patterns in the Biomarkers of Exposure to ARsenic (BEAR) prospective pregnancy cohort. This cohort includes residents from Gómez Palacio, located in the state of Durango in the Lagunera region of Northern Mexico. A total of 200 pregnant women residing in Gómez Palacio, State of Durango, Mexico, were recruited at the General Hospital of Gómez Palacio to participate in the BEAR prospective pregnancy cohort. The present study focuses on gene expression profiles and utilizes 38 samples obtained from mother-newborn pairs selected from the larger cohort (n=200). The subcohort was selected to include subjects exposed to varying levels of arsenic as determined by both total arsenic in maternal urine (U-tAs) and inorganic arsenic in drinking water (DW-iAs). Cord blood samples were collected from the newborns immediately after infant delivery. Blood samples were collected using PreAnalytix PaxGene RNA tubes and extracted using the PAXgene RNA Kit, per standard protocol (Qiagen, Valencia, CA). Isolated RNA used for microarray analysis were amplified and labeled using the NuGEN Ovation Pico WTA System V2 and Encore Biotin Module, respectively (NuGEN, San Carlos, CA). RNA isolated from 38 cord blood samples were labeled and hybridized to the Affymetrix Human Gene 2.0 ST Array.
2014-01-22 | E-GEOD-48354 | biostudies-arrayexpress
Project description:The Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gómez Palacio, Mexico was recently established to better understand the impacts of prenatal exposure to inorganic arsenic (iAs). In this study, we examined a subset (n = 40) of newborn cord blood samples for microRNA (miRNA) expression changes associated with in utero arsenic exposure. Levels of iAs in maternal drinking water (DW-iAs) and maternal urine were assessed. Levels of DW-iAs ranged from below detectable values to 236 µg/L (mean = 51.7 µg/L). Total arsenic in maternal urine (U-tAs) was defined as the sum of iAs and its monomethylated and dimethylated metabolites (MMAs and DMAs, respectively) and ranged from 6.2 to 319.7 µg/L (mean = 64.5 µg/L). Genome-wide miRNA expression analysis of cord blood revealed 12 miRNAs with increasing expression associated with U-tAs. Transcriptional targets of the miRNAs were computationally predicted and subsequently assessed using transcriptional profiling. Pathway analysis demonstrated that the U-tAs-associated miRNAs are involved in signaling pathways related to known health outcomes of iAs exposure including cancer and diabetes mellitus. Immune response-related mRNAs were also identified with decreased expression levels associated with U-tAs, and predicted to be mediated in part by the arsenic-responsive miRNAs. Results of this study highlight miRNAs as novel responders to prenatal arsenic exposure that may contribute to associated immune response perturbations.
2014-01-22 | GSE48354 | GEO
Project description:The Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gómez Palacio, Mexico was recently established to better understand the impacts of prenatal exposure to inorganic arsenic (iAs). In this study, we examined a subset (n = 40) of newborn cord blood samples for microRNA (miRNA) expression changes associated with in utero arsenic exposure. Levels of iAs in maternal drinking water (DW-iAs) and maternal urine were assessed. Levels of DW-iAs ranged from below detectable values to 236 µg/L (mean = 51.7 µg/L). Total arsenic in maternal urine (U-tAs) was defined as the sum of iAs and its monomethylated and dimethylated metabolites (MMAs and DMAs, respectively) and ranged from 6.2 to 319.7 µg/L (mean = 64.5 µg/L). Genome-wide miRNA expression analysis of cord blood revealed 12 miRNAs with increasing expression associated with U-tAs. Transcriptional targets of the miRNAs were computationally predicted and subsequently assessed using transcriptional profiling. Pathway analysis demonstrated that the U-tAs-associated miRNAs are involved in signaling pathways related to known health outcomes of iAs exposure including cancer and diabetes mellitus. Immune response-related mRNAs were also identified with decreased expression levels associated with U-tAs, and predicted to be mediated in part by the arsenic-responsive miRNAs. Results of this study highlight miRNAs as novel responders to prenatal arsenic exposure that may contribute to associated immune response perturbations.
2014-01-22 | GSE48353 | GEO
Project description:Prenatal exposure to inorganic arsenic (iAs) is detrimental to the health of newborns and increases the risk of disease development later in life. Here we examined a subset of newborn cord blood leukocyte samples collected from mothers enrolled in the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gomez Palacio, Mexico who were exposed to a range of drinking water arsenic concentrations (0.456-236 µg/L). Changes in iAs-associated DNA 5-methyl cytosine methylation were assessed across 424,935 CpG sites representing 18,761 genes and were compared to corresponding expression levels and birth outcomes. In the context of arsenic exposure, a total of 2,705 genes were identified with iAs-associated differences in DNA methylation. Site-specific analyzes identified DNA methylation changes that were most predictive of gene expression levels. Specifically, CpG methylation within CpG islands positioned within the first exon and 200bp upstream of the transcription start site yielded the most significant association with gene expression levels. A set of 16 genes was identified with correlated iAs-associated changes in DNA methylation and mRNA expression and all were highly enriched for binding sites of the early growth response (EGR) and CCCTC-binding factor (CTCF) transcription factors. Furthermore, DNA methylation levels of seven of these genes were associated with differences in birth outcomes including gestational age, placental weight and head circumference. These data highlight the complex interplay between DNA methylation and functional changes in gene expression and health outcomes and underscore the need for functional analyzes coupled to epigenetic assessments. 48 DNA methylation profiles were obtained but only 38 samples corresponding to samples also analyzed for gene expression (see Rager 2014) were further normalized and used in the publication from the Biomarkers of Arsenic (BEAR) cohort were analyzed for DNA methylation profiles.
2014-11-03 | E-GEOD-62924 | biostudies-arrayexpress
Project description:Prenatal exposure to inorganic arsenic (iAs) is detrimental to the health of newborns and increases the risk of disease development later in life. Here we examined a subset of newborn cord blood leukocyte samples collected from mothers enrolled in the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gomez Palacio, Mexico who were exposed to a range of drinking water arsenic concentrations (0.456-236 µg/L). Changes in iAs-associated DNA 5-methyl cytosine methylation were assessed across 424,935 CpG sites representing 18,761 genes and were compared to corresponding expression levels and birth outcomes. In the context of arsenic exposure, a total of 2,705 genes were identified with iAs-associated differences in DNA methylation. Site-specific analyzes identified DNA methylation changes that were most predictive of gene expression levels. Specifically, CpG methylation within CpG islands positioned within the first exon and 200bp upstream of the transcription start site yielded the most significant association with gene expression levels. A set of 16 genes was identified with correlated iAs-associated changes in DNA methylation and mRNA expression and all were highly enriched for binding sites of the early growth response (EGR) and CCCTC-binding factor (CTCF) transcription factors. Furthermore, DNA methylation levels of seven of these genes were associated with differences in birth outcomes including gestational age, placental weight and head circumference. These data highlight the complex interplay between DNA methylation and functional changes in gene expression and health outcomes and underscore the need for functional analyzes coupled to epigenetic assessments.
2014-11-03 | GSE62924 | GEO
Project description:The long-term health outcome of prenatal exposure to arsenic has been associated with increased mortality in human populations. In this study, the extent to which maternal arsenic exposure impacts gene expression in the newborn was addressed. We monitored gene expression profiles in a population of newborns whose mothers experienced varying levels of arsenic exposure during pregnancy. Through the application of machine learning-based two-class prediction algorithms, we identified expression signatures from babies born to arsenic-unexposed and -exposed mothers that were highly predictive of prenatal arsenic exposure in a subsequent test population. Furthermore, 11 transcripts were identified that captured the maximal predictive capacity to classify prenatal arsenic exposure. Network analysis of the arsenic-modulated transcripts identified the activation of extensive molecular networks that are indicative of stress, inflammation, metal exposure, and apoptosis in the newborn. Exposure to arsenic is an important health hazard both in the United States and around the world, and is associated with increased risk for several types of cancer and other chronic diseases. These studies clearly demonstrate the robust impact of a mother's arsenic consumption on fetal gene expression as evidenced by transcript levels in newborn cord blood.
| S-EPMC2082467 | biostudies-literature
Project description:In the present study, we employed the RNA sequencing platform to examine the molecular response of zebrafish liver to arsenic exposure and carry out detailed transcriptomic analyses for further understanding of molecular toxicity. We found that several important biological processes were perturbed by arsenic exposure, including oxidation reduction, translation, iron ion transport, cell redox and homeostasis, as well as related pathways in metabolism and diseases. Furthermore, as there are currently no biomarker genes available for predicting arsenic exposure, we took the advantage of RNA sequencing platform to identify most suitable biomarker genes from top responsive genes to arsenic exposure. We first validated these top responsive genes by RT-qPCR in zebrafish and then in Japanese medaka (Oryzias latipes) at individual fish level for more robustly responsive genes across different fish species. Transcriptome profiling of arsenic-treated sample and control sample were generated by deep sequencing using 3' RNA-SAGE on the SOLiD system.
2013-09-04 | E-GEOD-48427 | biostudies-arrayexpress
Project description:Arsenic is environmental risk factor and has been linked to urothelial carcinoma incidence. Arsenic exposure-induced malignant transformed cells was established from normal urothelial cells by chronic arsenic exposure for 10 months. The purpose of the present study is to elucidate the relevant molecular alterationon on arsenic-induced malignant transformation.
2016-11-19 | GSE90023 | GEO