Identification of transcriptome and metabolome signatures of fatty liver disease in HepaRG cells exposed to PCB 126 and glyphosate
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE109565 | GEO | 2019/01/10
REPOSITORIES: GEO
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Project description:Identification of transcriptome and metabolome signatures of fatty liver disease in HepaRG cells exposed to PCB 126 and glyphosate
| PRJNA431399 | ENA
Project description:Human health effects from chronic exposure to pesticide residues are little investigated. We compared standard histopathology and serum biochemistry measures and multi-omics analyses in an in vivo subchronic toxicity test of a glyphosate, its formulated product MON 52276, and mixture of six pesticide active ingredients frequently detected in foodstuffs (azoxystrobin, boscalid, chlorpyrifos, glyphosate, imidacloprid and thiabendazole). Sprague-Dawley rats were administered with the pesticide mixture with each ingredient at its regulatory permitted acceptable daily intake.
2021-04-12 | GSE157426 | GEO
Project description:Human health effects from chronic exposure to pesticide residues are little investigated. We compared standard histopathology and serum biochemistry measures and multi-omics analyses in an in vivo subchronic toxicity test of a glyphosate, its formulated product MON 52276, and mixture of six pesticide active ingredients frequently detected in foodstuffs (azoxystrobin, boscalid, chlorpyrifos, glyphosate, imidacloprid and thiabendazole). Sprague-Dawley rats were administered with the pesticide mixture with each ingredient at its regulatory permitted acceptable daily intake.
2021-04-12 | GSE157551 | GEO
Project description:Glyphosate is one of the most widely used herbicides globally. It acts by inhibiting an enzyme in an aromatic amino synthesis pathway specific to plants and microbes, leading to view that glyphosate poses no risk to other organisms. However, there is growing concern that glyphosate is associated with detrimental health effects in humans, and an ever-increasing body of evidence suggests that glyphosate affects other animals including pollinating insects such as bees. Although pesticides have long been considered a contributing factor in the decline of wild bee populations most research on bees has focussed on demonstrating and understanding the effects (particularly sublethal ones) of insecticides. To assess whether glyphosate poses a potential risk to bees we characterised the changes in survival, behaviour, digestive tract proteome and microbiome in the bumblebee Bombus terrestris after chronic exposure to field relevant doses of glyphosate alone and as part of the commercially available product RoundUp Optima+®. Regardless of source, changes in response to herbicide exposure in important cellular and physiological processes in the digestive tract of B. terrestris were observed, with the abundances of proteins associated with oxidative stress regulation, metabolism, cellular adhesion, the extracellular matrix, and various signalling pathways being altered. Interestingly, endocytosis, oxidative phosphorylation, the TCA cycle, and carbohydrate, lipid, and amino acid metabolism were differentially altered depending on whether the exposure source was glyphosate AI or RoundUp Optima+®. In addition, RoundUp Optima+®, but not the active ingredient glyphosate, impacted fungal diversity in the digestive tract microbiota. Our research provides new insights into the potential mode of action and consequences of glyphosate exposure at the molecular and cellular levels in bumblebees and highlights issues with current regulatory measures involving commercial formulations of pesticides where the impact of the co-formulants on non-target organisms are generally overlooked.
2023-07-01 | PXD036578 | Pride
Project description:Glyphosate is known to inhibit 5-enolpyruvylshikimate-3-phosphate synthase of the chorismate biosynthetic pathway, and chorismate is a precursor to aromatic amino acids, auxin, and many other secondary products. Although the perennial weed leafy spurge (Euphorbia esula L.) is considered glyphosate tolerant, glyphosate is often used as part of an integrated pest management program in non-cultivated ecosystems of North America. Part of its tolerance is attributed to escape through an abundance of underground adventitious buds (UABs). Sub-lethal concentrations of foliar applied glyphosate leads to new shoot growth from UABs that have a stunted and/or bushy phenotype after growth-inducing decapitation. To gain insights into glyphosateM-bM-^@M-^Ys impact on molecular mechanisms associated with the stunted and bushy phenotype, we obtained global transcriptome abundance using RNAseq from a subsequent generation of aerial shoots derived from crown buds of glyphosate-treated and -untreated leafy spurge. We further correlated transcript abundance to accumulation of shikimate and phytohormones from the same samples to elucidate interactions. Abundance of shikimate was similar in subsequent generations of aerial shoots generated from crown buds of treated and untreated plants and is likely not a direct factor leading to the stunted and bushy phenotype. However, the results do suggest that transcripts involved in auxin transport and signaling and crosstalk with other phytohormones likely play a role in the bushy phenotype. The results of this study provide some insights for identifying new targets for manipulation of plant growth and development. Transcriptome and metabolite profiling are obtained for aerial tissues derived from crown buds of foliar glyphosate-treated and control (2.24 or 0 kg/ha active ingredient glyphosate + 0.25% v/v surfactant) leafy spurge plants. Each experiment included 4 biological replicates.
2014-04-15 | E-GEOD-56509 | biostudies-arrayexpress
Project description:Background: Herbicides are environmental contaminants that have gained much attention due to the potential hazards they pose to human health. Glyphosate, the active ingredient in many commercial herbicides, is the most heavily applied herbicide worldwide. The recent rise in glyphosate application to corn and soy crops correlates positively with increased death rates due to Alzheimer's disease and other neurodegenerative disorders. Glyphosate has been shown to cross the blood-brain barrier in in vitro models, but has yet to be verified in vivo. Additionally, reports have shown that glyphosate exposure increases pro-inflammatory cytokines in blood plasma, particularly TNFα. Methods: Here, we examined whether glyphosate infiltrates the brain and elevates TNFα levels in 4-month-old C57BL/6J mice. Mice received either 125, 250, or 500 mg/kg/day of glyphosate, or a vehicle via oral gavage for 14 days. Urine, plasma, and brain samples were collected on the final day of dosing for analysis via UPLC-MS and ELISAs. Primary cortical neurons were derived from amyloidogenic APP/PS1 pups to evaluate in vitro changes in Aβ40-42 burden and cytotoxicity. RNA sequencing was performed on C57BL/6J brain samples to determine changes in the transcriptome. Results: Our analysis revealed that glyphosate infiltrated the brain in a dose-dependent manner and upregulated TNFα in both plasma and brain tissue post-exposure. Notably, glyphosate measures correlated positively with TNFα levels. Glyphosate exposure in APP/PS1 primary cortical neurons increases levels of soluble Aβ40-42 and cytotoxicity. RNAseq revealed over 200 differentially expressed genes in a dose-dependent manner and cell-type-specific deconvolution analysis showed enrichment of key biological processes in oligodendrocytes including myelination, axon ensheathment, glial cell development, and oligodendrocyte development. Conclusions: Collectively, these results show for the first time that glyphosate infiltrates the brain, elevates both the expression of TNFα and soluble Aβ, and disrupts the transcriptome in a dose-dependent manner, suggesting that exposure to this herbicide may have detrimental outcomes regarding the health of the general population.
2024-01-15 | GSE253299 | GEO
Project description:Using whole genome microarray (Affymetrix ATH1) we studied the transcriptional response of Arabidopsis thaliana to glyphosate (Roundup Original) herbicde that inhibits 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) enzyme and thus disrupts aromaticamino acid biosynthesis. Few genes related to defense and secondary metabolism were altered. Experiment Overall Design: Surfactant (preference 0.25%) treated plants were used as carrier control group and EC50 concentration of glyphosate was used as the herbicide treatment group. Each of the control and treatment group consisted of 3 biological replicates and each biological replicates comprised leaves from 10 individual plants. RNA was extracted at 24h post treatment to study the transcriptional alterations caused by the herbicide treatment.
2009-08-07 | E-GEOD-8927 | biostudies-arrayexpress
Project description:Total transcript amplification (TTA) from single eukaryotic cells for transcriptome analysis is established, but TTA from a single prokaryotic cell presents additional challenges with much less starting material and lack of poly(A)-tails. We described, here, a novel method for single bacterium TTA, using a Burkholderia thailandensis model exposed to subinhibitory concentration of the antibacterial agent, glyphosate. Utilizing B. thialandensis microarray to assess the TTA method showed little gene bias (< 2 fold-change) and absence (~5-6%) when compared to the larger scale non-amplified RNA samples. B. thailandensis genes important to possibly recuperate and balance the intracellular amino acid pool were induced (or repressed) by the aromatic amino acid biosynthesis inhibitor, glyphosate. We validated our single-cell microarray data at the multi-cells and single-cell levels with lacZ and gfp reporter-gene fusions, respectively. This novel method will rejuvenate and expand the prokaryotic transcriptomic field. Two identical cultures of B. thailandensis wildtype strain E264 were grown in 1x M9 minimal medium supplemented with 1% Brij-58 and 20 mM glucose (MG) to mid-log phase. One culture was induced by final concentration of 0.01% (w/v) glyphosate for 30 minutes. Total RNA was then purified from B. thailandensis uninduced and induced samples, converted to cDNA and hybridized onto B. thailandensis 70mer triplicate array
2010-08-05 | E-GEOD-23419 | biostudies-arrayexpress
Project description:Chemical pollutant exposure is a risk factor contributing to the growing epidemic of non-alcoholic fatty liver disease (NAFLD) affecting human populations that consume a western diet. Although it is recognized that intoxication by chemical pollutants can lead to NAFLD, there is limited information available regarding the mechanism by which typical environmental levels of exposure can contribute to the onset of this disease. Here, we describe the alterations in gene expression profiles and metabolite levels in the human HepaRG liver cell line, a validated model for cellular steatosis, exposed to the polychlorinated biphenyl (PCB) 126, one of the most potent chemical pollutants that can induce NAFLD. Sparse partial least squares classification of the molecular profiles revealed that exposure to PCB 126 provoked a decrease in polyunsaturated fatty acids as well as an increase in sphingolipid levels, concomitant with a decrease in the activity of genes involved in lipid metabolism. This was associated with an increased oxidative stress reflected by marked disturbances in taurine metabolism. A gene ontology analysis showed hallmarks of an activation of the AhR receptor by dioxin-like compounds. These changes in metabolome and transcriptome profiles were observed even at the lowest concentration (100 pM) of PCB 126 tested. A decrease in docosatrienoate levels was the most sensitive biomarker. Overall, our integrated multi-omics analysis provides mechanistic insight into how this class of chemical pollutant can cause NAFLD. Our study lays the foundation for the development of molecular signatures of toxic effects of chemicals causing fatty liver diseases to move away from a chemical risk assessment based on in vivo animal experiments.
| S-EPMC6063328 | biostudies-literature
Project description:Glyphosate is the herbicide most used worldwide, with no historic comparison. It is used for genetically modified crops, and particularly in Florida, it is used as a sugar cane ripener. It is also formulated to treat aquatic weeds in waterbodies as Rodeo®. Because of its extended use, it can run off or be sprayed directly into waterbodies and aquatic wildlife can be chronically exposed. Exposure in animal models has been associated with kidney and liver damage and it has been suggested as an endocrine disruptor. We exposed adult male largemouth bass for 21 days to two doses of glyphosate and Rodeo (chemically equivalent concentration of glyphosate) including 0.5 mg/L and 10 mg/L and to clean water as a control (n=4/tank in quadruplicate). Concentrations during the experiment were corroborated with LC-MS/MS. Total RNA was isolated from the trunk kidney and head kidney. RNA-seq was performed for the high doses compared to controls (n=4/treatment). Transcripts were analyzed with fish and mammalian pathway analyses. Transcripts mapped to Zebrafish metabolic pathways using Paintomics showed the most significantly enriched pathway was steroid hormone biosynthesis in the trunk kidney. Steroid hormones were measured in plasma by LC-MS/MS. Total androgens were significantly reduced at 0.5 mg/L of glyphosate and Rodeo compared to control. While 11-ketotestosterone and estrone concentration was significantly reduced in all doses. Our results show a possible down regulation of the conversion of testosterone to 11-ketotestosterone by glyphosate and Rodeo at concentrations that are allowed in U.S drinking water. Using the mammalian pathway analysis algorithm, cellular processes associated with T-cell activation/development and intracellular pH were significantly enriched in the trunk kidney after glyphosate and Rodeo exposure. Glyphosate and Rodeo produce endocrine disruption corroborated at the hormone and gene expression level. Rodeo and glyphosate share gene expression pathways, however, Rodeo had more pronounced effects in largemouth bass.
2022-04-20 | GSE197375 | GEO