RNA-seq of the liver tissue from female F1 generation with parternal exposure to arsenic in drinking water
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE154130 | GEO | 2021/04/14
REPOSITORIES: GEO
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Project description:Adult male mice (F0) were exposed to 250 ppb inorganic arsenic (iAs) in drinking water before mating with unexposed female mice to generate male F1 offspring (iAsF1-M). Unexposed male mice were bred simultaneously to generate male controls (conF1-M). Both iAsF1-M and conF1-M mice drank normal water without iAs. Adult iAsF1-M and conF1-M mice were harvested to collect liver samples to do RNA-seq.
2023-09-13 | GSE205355 | GEO
Project description:Pregnant C3H mice were given tap water (control group) and tap water containing 85 ppm sodium arsenite from gestational day 8 to 18 (arsenic group), respectively. The DNA methylomes of sperm of F1 mice were investigated by RRBS method. The results showed that gestational arsenic exposure increased hypomethylated cytosines in the F1 sperm genome. The present study has indicated environmental impacts on sperm DNA methylome establishment.
2020-12-08 | GSE150500 | GEO
Project description:Inorganic arsenic (iAs) is a widespread environmental toxin. In addition to being a human carcinogen, its effect on systemic glucose metabolism has started to gain recognition recently. However, its in vivo effect on insulin sensitivity is not clear. Here we use mouse models to dissect the dose-dependent effects of iAs in glucose metabolism. We found that a low-dose exposure (0.25 ppm iAs in drinking water) caused glucose intolerance in adult male C57BL/6 mice, likely by disrupting glucose-induced insulin secretion without affecting peripheral insulin sensitivity. However, a higher-dose exposure (2.5 ppm iAs) has diminished effects on glucose tolerance despite disrupted pancreatic insulin secretion. We performed hyperinsulinemic euglycemic clamp, the gold standard analysis of systemic insulin sensitivity, and found that the 2.5 ppm iAs enhanced systemic insulin sensitivity by simultaneously enhancing insulin-stimulated glucose uptake in skeletal muscles and insulin-mediated suppression of endogenous glucose production. RNA-seq analysis of muscles revealed that 2.5 ppm iAs regulated expression of many genes involved in the metabolism of fatty acids, pyruvate, and amino acids. These findings suggest that iAs has distinct effects on distinct metabolic tissues at different dose thresholds, which could help reconcile some of the conflicting epidemiological results. The study shed light on the complex interactions between an environmental factor and the systemic glucose metabolism.
2018-11-16 | GSE122566 | GEO
Project description:Pregnant C3H mice were given tap water (control group) and tap water containing 85 ppm sodium arsenite from gestational day 8 to 18 (arsenic group), respectively. The DNA methylomes of sperm of F1 mice were investigated by RRBS method. The results showed that gestational arsenic exposure increased hypomethylated cytosines in active retrotransposon subfamilies. The present study has indicated environmental impacts on sperm DNA methylome establishment.
2020-12-08 | GSE150650 | GEO
Project description:In this study, we examined the effect of inorganic arsenic (iAs) on the estrogen response (E2) in MCF-7 cells that are estrogen receptor positive/progesterone receptor positive (ER+/PR+). Understanding the changes in the transcriptomic response after iAs exposure and the retention of such responses during recovery from iAs exposure can identify driver mechanisms of breast cancer progression and improve therapies for patients with ER+ cancers exposed to iAs.
2020-10-21 | E-MTAB-9498 | biostudies-arrayexpress
Project description:Inorganic arsenic, a major environmental contaminant, has risen as an important health problem worldwide. More detailed identification of the molecular mechanisms associated with iAs exposure would help to establish better strategies for prevention and treatment. Although chronic iAs exposures have been previously studied there is little to no information regarding the early events of exposure to iAs. To better characterize the early mechanisms of iAs exposure we conducted gene expression studies using sublethal doses of iAs at two different time-points. The major transcripts differentially regulated at 2 hrs of iAs exposure included antioxidants, detoxificants and chaperones. Moreover, after 12 hrs of exposure many of the down-regulated genes were associated with DNA replication and S phase cell cycle progression. Interestingly, the most affected biological pathway by both 2 or 12 hrs of iAs exposure were the Nrf2-Keap1 pathway, represented by the highly up-regulated HMOX1 transcript, which is transcriptionally regulated by the transcription factor Nrf2. Additional Nrf2 targets included SQSTM1 and ABCB6, which were not previously associated with acute iAs exposure. Signalling pathways such as interferon, B cell receptor and AhR route were also responsive to acute iAs exposure. Since HMOX1 expression increased early (20 min) and was responsive to low iAs concentrations (0.1 M), this gene could be a suitable early biomarker for iAs exposure. In addition, the novel Nrf2 targets SQSTM1 and ABCB6 could play an important and previously unrecognized role in cellular protection against iAs
2013-10-24 | GSE51454 | GEO
Project description:There is strong epidemiologic evidence supporting that exposure to inorganic arsenic (iAs) exposure is responsible for a myriad of adverse health effects, including carcinogenesis of the bladder. This research aimed to identify novel epigenetic biomarkers of iAs exposure in target cells within a human population. Here we assessed genome-wide, gene-specific promoter DNA methylation levels assessed in exfoliated human bladder uroepithelial cells (BECs) in relationship to BEC iAs, monomethylated As (MMAs), dimethylated As (DMAs), and total As (tAs) concentrations from 46 individuals with varying levels of As exposure in Chihuahua, Mexico. These analyses identified genes with increased methylation associated with BEC iAs(III+V), MMAs(III+V), and tAs(III+V). These genes were enriched for signaling related to metabolic disease and cancer.
2015-06-01 | GSE58499 | GEO
Project description:Inorganic arsenic, a major environmental contaminant, has risen as an important health problem worldwide. More detailed identification of the molecular mechanisms associated with iAs exposure would help to establish better strategies for prevention and treatment. Although chronic iAs exposures have been previously studied there is little to no information regarding the early events of exposure to iAs. To better characterize the early mechanisms of iAs exposure we conducted gene expression studies using sublethal doses of iAs at two different time-points. The major transcripts differentially regulated at 2 hrs of iAs exposure included antioxidants, detoxificants and chaperones. Moreover, after 12 hrs of exposure many of the down-regulated genes were associated with DNA replication and S phase cell cycle progression. Interestingly, the most affected biological pathway by both 2 or 12 hrs of iAs exposure were the Nrf2-Keap1 pathway, represented by the highly up-regulated HMOX1 transcript, which is transcriptionally regulated by the transcription factor Nrf2. Additional Nrf2 targets included SQSTM1 and ABCB6, which were not previously associated with acute iAs exposure. Signalling pathways such as interferon, B cell receptor and AhR route were also responsive to acute iAs exposure. Since HMOX1 expression increased early (20 min) and was responsive to low iAs concentrations (0.1 M-oM-^AM--M), this gene could be a suitable early biomarker for iAs exposure. In addition, the novel Nrf2 targets SQSTM1 and ABCB6 could play an important and previously unrecognized role in cellular protection against iAs We used human lymphoblastoid cell line (CL-1), immortalized with Epstein-Barr virus. Cell cultures were propagated in RPMI media supplemented with 10% fetal bovine serum (FBS), L-glutammine 2 mM and antiobiotics penicillin and 10 mg/ml streptomycin) at 37M-BM-:C in an atmosphere of 5% CO2. In the case of primary cultures, 1% phytohemaglutinine were added. Cell cultures (1x106) were treated with 5M-BM-5M sodium arsenite for 2 and 12 hrs while control cultures were incubated with PBS. Nine biological replicates for each condition were used for microarray analysis. After iAs treatment, total RNA from each biological replicate was isolated with Trizol. From the 9 biological replicates performed on each condition, we generated 3 pools at a concentration of 300 ng/M-BM-5L, where each pool was processed to a single microarray platform.
2013-10-24 | E-GEOD-51454 | biostudies-arrayexpress
Project description:Chronic exposure to inorganic arsenic (iAs) or a high-fat diet (HFD) can produce liver injury. However, the interactive molecular biological effects and mechanism of iAs and HFD are as of yet unclear. We used microarrays to detail the interactive effects of arsenic and a high-fat diet on hepatic gene expression. The C57BL/6 Mice fed low-fat diet (LFD) or HFD were exposed to 3 mg/L iAs or deionized water for 10 weeks. Then, hepatic RNA were extraction and hybridization on Affymetrix microarrays. Differentially expressed genes in LFD+As, HFD, and HFD+As groups compared to LFD group were identified, and interactive molecular biological effects and mechanism of iAs and HFD were discussed.
2013-11-30 | E-GEOD-52702 | biostudies-arrayexpress
Project description:Background: Chronic exposure to inorganic arsenic (iAs) has been associated with type 2 diabetes (T2D). However, potential sex divergence and the underlying mechanisms remain understudied. iAs is not metabolized uniformly across species, which is a limitation of typical exposure studies in rodent models. The development of a new “humanized” mouse model overcomes this limitation. In this study, we leverage this model to study sex differences in the context of iAs exposure. Objectives: The aim of this study iwas to determine if males and females exhibit different liver and adipose molecular profiles and metabolic phenotypes in the context of iAs exposure. Methods: Our study was performed on wild-type (WT) 129S6/SvEvTac and humanized arsenic +3 methyl transferase (human AS3MT) 129S6/SvEvTac mice treated with 400 ppb of iAs via drinking water ad libitum. After 1 month, mice were sacrificed and the liver and epididymales gonadal adipose depot were harvested for iAs quantification as well as sequencing-based microRNA and gene expression analysis. Serum blood was collected for fasting blood glucose, fasting plasma insulin, and HOMA-IR. Results: We detected sex divergence in liver and adipose markers of diabetes (e.g., insulin signaling pathways, fasting blood glucose, fasting plasma insulin, and HOMA-IR) only in humanized (not WT) male mice. In humanized female mice, numerous genes that promote insulin sensitivity and glucose tolerance in both the liver and adipose are elevated compared to humanized male mice. We also identified Klf11 as a putative master regulator of the sex divergence in gene expression in humanized mice. Discussion: Our study underscoreds the importance of future studies leveraging the humanized mouse model to study iAs-associated metabolic disease. The findings also suggest suggested that humanized females are protected from metabolic dysfunction relative to humanized males in the context of iAs exposure. Future investigations should focus on the detailed mechanisms that underlie the sex divergence, including the potential role of miR-34a and/or Klf11.
2023-07-03 | GSE236059 | GEO