Liver Cyprinus carpio PFOS experiment
Ontology highlight
ABSTRACT:
ORGANISM(S): Cyprinus carpio
PROVIDER: GSE10980 | GEO | 2008/08/15
SECONDARY ACCESSION(S): PRJNA107179
REPOSITORIES: GEO
Similar Datasets
Project description:Perfluorooctane sulfonate (PFOS) has been manufactured for over 50 years in increasing quantities and has been used for several industrial and commercial aims. Due to the persistence and the bioaccumulation of this pollutant, it can be found worldwide in wildlife and humans. Biochemical effects of PFOS exposure are mainly studied in mammalian model species and information about effects on fish species remain largely scarce. This lack of toxicity data points out that there is an urgent need for the mechanistic molecular understanding of the mode of action of this pollutant. In the present study, common carp (Cyprinus carpio) was exposed through water for 14 days at concentrations of 0.1; 0.5 and 1 mg/l PFOS. Liver was selected as target tissue. Custom microarrays were constructed from cDNA libraries obtained with Suppression Subtractive Hybridization-Polymerase chain reaction (SSH-PCR) experiments. Microarray data revealed that the expression of several genes in the liver was influenced by PFOS exposure and real-time PCR was used to confirm these gene expression changes. The affected genes were mainly involved in energy metabolism, reproduction and stress response. Furthermore, the relative condition factor and the hepatosomatic index of the exposed fish were significantly lower after 14 days of exposure as well as the available glycogen reserves. At all levels of biological organization, indications of a trade-off between the metabolic cost of toxicant exposure on one hand and processes vital to the survival of the organism on the other hand were seen. Our results support the prediction that increases in energy expenditure negatively affects processes vital to the survival of an organism, such as growth. Keywords: PFOS, common carp, microarray, condition factor, energy reserves, metabolic cost There were 3 biological replicates for each exposure concentration. For each biological replicate control versus exposed hybridizations were carried out. The mean of the biological replicates was calculated for the differentially expressed genes.
2008-08-15 | E-GEOD-10980 | biostudies-arrayexpress
Project description:Fluorosurfactants are the key components in aqueous film forming foams (AFFF). They provide these fire fighting agents with the required low surface tension and they enable film formation on top of lighter fuels to prevent burn back. Development of effective and environmentally acceptable PFOS alternatives is one of the most important priorities in the fire fighting foam industry. DuPontTM offers the fluorosurfactant mixtures Forafac®1157 and Forafac®1157N for the formulation of AFFFs which are alternatives to the persistent and toxic perfluorooctane sulphonate (PFOS). Ecotoxicological testing of these inadequately documented mixtures is necessary to include them in AFFF hazard and risk assessment. Juvenile turbot (Scophthalmus maximus) was exposed for 14 days to 0.5 and 1.5 mg/l of the fluorosurfactant mixtures used in Forafac®1157 and Forafac®1157N. In a first transcriptomics experiment, microarray analysis revealed differentially expressed gene transcripts which were mainly involved in digestion and in the immune system. This discovery-driven screening approach offered the basis for new hypotheses that were tested in two subsequent experiments in which food intake, energy reserves, growth and a set of haematological parameters were examined. Additionally, effects of the two mixtures were compared to those of PFOS. Based on the results of this study, the mode of action of Forafac®1157N was the activation of the acute phase reaction resulting in increased leukocyte concentrations and the inhibition of growth due to the high energetic cost of toxicant exposure. For Forafac®1157, evidences of immunosuppression were found on the transcriptional level and the altered differential leukocyte profiles indicated that stress was induced in these fish. However, food intake, energy reserves and growth were not compromised, even at high exposure concentrations, which was in contrast to the effects seen after PFOS exposure. Taking into account that Forafac®1157 appeared to be less toxic than PFOS, this mixture could be considered as a more environmentally acceptable PFOS alternative for the use in AFFFs.
2011-05-22 | GSE28488 | GEO
Project description:Fluorosurfactants are the key components in aqueous film forming foams (AFFF). They provide these fire fighting agents with the required low surface tension and they enable film formation on top of lighter fuels to prevent burn back. Development of effective and environmentally acceptable PFOS alternatives is one of the most important priorities in the fire fighting foam industry. DuPontTM offers the fluorosurfactant mixtures Forafac®1157 and Forafac®1157N for the formulation of AFFFs which are alternatives to the persistent and toxic perfluorooctane sulphonate (PFOS). Ecotoxicological testing of these inadequately documented mixtures is necessary to include them in AFFF hazard and risk assessment. Juvenile turbot (Scophthalmus maximus) was exposed for 14 days to 0.5 and 1.5 mg/l of the fluorosurfactant mixtures used in Forafac®1157 and Forafac®1157N. In a first transcriptomics experiment, microarray analysis revealed differentially expressed gene transcripts which were mainly involved in digestion and in the immune system. This discovery-driven screening approach offered the basis for new hypotheses that were tested in two subsequent experiments in which food intake, energy reserves, growth and a set of haematological parameters were examined. Additionally, effects of the two mixtures were compared to those of PFOS. Based on the results of this study, the mode of action of Forafac®1157N was the activation of the acute phase reaction resulting in increased leukocyte concentrations and the inhibition of growth due to the high energetic cost of toxicant exposure. For Forafac®1157, evidences of immunosuppression were found on the transcriptional level and the altered differential leukocyte profiles indicated that stress was induced in these fish. However, food intake, energy reserves and growth were not compromised, even at high exposure concentrations, which was in contrast to the effects seen after PFOS exposure. Taking into account that Forafac®1157 appeared to be less toxic than PFOS, this mixture could be considered as a more environmentally acceptable PFOS alternative for the use in AFFFs. Juvenile turbot with a mean weight of 7.21 ± 1.91 g and a mean length of 7.34 ± 0.33 cm were exposed to nominal concentrations of 0 mg/L; 0.5 mg/L and 1.5 mg/L for both Forafac®1157 and Forafac®1157N during 14 days. Three different 45 L aquaria per exposure condition were used resulting in 3 tank replicates. Each replicate aquarium contained six turbot. After decapitation, the liver was dissected, homogenized in liquid nitrogen and stored at -80 °C until further analysis. The liver homogenates of the 6 fish per aquarium of exposure experiment 1 were pooled prior to RNA extraction. After RNA extraction, fluorescently labelled cRNA was constructed with each sample labelled with Cy3 as well as with Cy5.An Agilent custom 15k oligonucleotide microarray (Agilent Technologies) was used to measure gene transcription levels. The microarray platform, constructed by ACUIGEN (University de Santiago de compostela, Spain), contained 4 305 turbot-specific oligonucleotide fragments originating from an immune-related EST turbot database. Two probe volumes (Cy3 vs. Cy5) corresponding with 300 ng cRNA were mixed and applied onto every microarray. The hybridization design comprised one separate n+2 A-optimal design for each of the Forafac® mixtures.
2011-05-22 | E-GEOD-28488 | biostudies-arrayexpress
Project description:Condition specific zebrafish metabolic models generated using the COBRA MetaboTools framework. The Wang et al., (2021) zebrafish genome-scale metabolic model (GEM) was constrained with experimental data from 5 days post fertilized (dpf) zebrafish to generate a 'base-model'.
In turn this 5 dpf zebrafish base-model was constrained with experimental (transcriptomics and metabolomics) data from 5 dpf zebrafish exposed to the environmental pollutant perfluorooctane sulfonate (PFOS), at three levels - Low (0.06 uM), Medium (0.6 uM), and High (2 uM) PFOS.
The MetaboTools framework was used to construct three condition-sepcific models: Low, Medium, and High PFOS.
Key simulation predictions of effects on the carnitine shuttle and lipid metabolism were confirmed in wild-caught fish and dolphins (stranded animals) sampled from the northern Gulf of Mexico - published in Nolen et al., (2024) https://doi.org/10.1016/j.cbpc.2023.109817
2024-03-04 | MODEL2403010004 | BioModels
Project description:Perfluorooctanesulfonic acid (PFOS) is a persistent, bio-accumulative pollutant that has been used for the last 60+ years in numerous industrial and commercial applications. In mice, PFOS administration is known to induce hepatomegaly and hepatic steatosis. The aim of the present study was to evaluate potential PFOS and diet interactions and explore the mechanism of PFOS induced liver lipid accumulation. Prior to PFOS administration, mice were fed either a standard chow diet (SD) or 60% kCal high fat diet (HFD) for 4 weeks to establish significant body weight increase. After 4 weeks of diet acclimation, the treatment groups received 0.0003% PFOS in diet for an additional 10 weeks. In addition, a subset of the mice fed HFD were switched to a SD (H-SD) to mimic weight-loss induced improvement of hepatic steatosis. A total of six treatment groups: i) SD, ii) HSD, iii) HFD (H), iv) SD +PFOS(SDP), v) H-SD +PFOS (HSDP), and vi) HFD +PFOS (HP) were included. PFOS and lipid concentrations were measured in both serum and liver. Relative liver mRNA expression was determined by targeted bead array and proteins were quantified using untargeted mass spectrometry. PFOS exposure increased liver weight, and in the HFD increased liver triglycerides and liver cholesterol content. Gene and protein expression in the liver demonstrated that PFOS exposure induced lipid utilization and xenobiotic metabolism pathways, and in a HFD, induced lipid synthesis. The data suggests that PFOS exposure acts on lipid utilization genes and exacerbates hepatic steatosis in mice fed a HFD.
2020-09-30 | PXD016161 | Pride
Project description:PFOS, a member of the chemical group known as per- and polyfluoroalkyl substances (PFAS), is a well-documented environmental contaminant. Its high bioaccumulation potential and long elimination half-life can disrupt multiple biological pathways negatively affecting human health. The gastrointestinal tract (GI) is directly exposed to environmental pollutants via contaminated drinking water and food, potentially influencing intestinal homeostasis under both physiological and pathological conditions. Although some studies have highlighted the potential role of PFOS in tumor development, scientific literature on PFOS exposure in the GI is limited and the association between this environmental pollutant and GI-associated diseases remains to be determined. Therefore, this study aims to delineate the effects of PFOS on normal intestinal cells. The effect of PFOS on gene expression profiles was assessed through RNAseq analysis conducted on the intestinal tissue of C57BL/6 mice. Through RNAseq analysis, we identified the top pathways upregulated by PFOS as cancer, lipid metabolism and immune system. The KEGG analysis further highlighted significant gene enrichment in pro-oncogenic signaling pathways, including NOTCH, WNT/β-catenin and TGF-β. The RNAseq, q-RT-PCR and western blot analyses of normal intestinal tissues revealed that PFOS exposure leads to downregulation of 3-hydroxy-3-methylglutaryl-Coa synthase 2 (HMGCS2), a key enzyme in the synthesis of β-hydroxybutyrate (βHB), a critical ketogenic molecule. In summary, our data suggests that PFOS may induce GI pathological changes that can increase the risk of CRC development. We identified that downregulation of ketogenesis and upregulation of lipid metabolism are the major effects of PFOS exposure in intestinal epithelium.
2024-06-12 | GSE248402 | GEO
Project description:Recently it was discovered that the perfluorooctane sulfonate (PFOS) detected in wildlife, such as fish-eating birds, had a greater proportion of linear PFOS (L-PFOS) than the manufactured technical product (T-PFOS), which contains linear and branched isomers. This suggests toxicological studies based on T-PFOS data may inaccurately assess exposure risk to wildlife. To determine if PFOS effects were influenced by isomer content we compared the transcriptional profiles of cultured chicken embryonic hepatocytes (CEH) exposed to either L-PFOS or T-PFOS using Agilent microarrays. At equal concentrations (10 μM), T-PFOS altered the expression of more transcripts (340, >1.5 fold change, p<0.05) compared to L-PFOS (130 transcripts). Higher concentrations of L-PFOS (40 μM) were also less transcriptionally disruptive (217 transcripts) than T-PFOS at 10 μM. Functional analysis showed that L-PFOS and T-PFOS affected genes involved in lipid metabolism, hepatic system development and cellular growth and proliferation. Pathway and interactome analysis suggested that genes may be affected through the RXR receptor, oxidative stress response, TP53 signaling, MYC signaling, Wnt/β-catenin signaling and PPARγ and SREBP receptors. In all functional categories and pathways examined, the response elicited by T-PFOS was greater than L-PFOS. These data show that T-PFOS elicits a greater transcriptional response in CEH than L-PFOS alone and demonstrates the importance of considering the isomer-specific toxicological properties of PFOS when assessing exposure risk. Reference Design. Reference = pool of equal parts of all control and treated samples. Control groups and 5 treatment groups. Control samples were CEH exposed DMSO only (vehicle solvent). Treatments were: CEH exposed to 10 uM L-PFOS, 40 uM L-PFOS, 10 uM T-PFOS, 0.03 nM TCDD and 1 nM TCDD.
2011-10-28 | E-GEOD-33291 | biostudies-arrayexpress
Project description:Limited studies on multi-omics have been conducted to comprehensively investigate the molecular mechanism underlying the developmental neurotoxicity of perfluorooctanesulfonic acid (PFOS). In this study, the locomotor behavior of zebrafish larvae was assessed under the exposure to 0.1–20 μM PFOS based on its reported neurobehavioral effect. After the number of zebrafish larvae was optimized for proteomics and metabolomics studies, three kinds of omics (i.e., transcriptomics, proteomics, and metabolomics) were carried out with zebrafish larvae exposed to 0.1, 1, 5, and 10 μM PFOS. More importantly, a data-driven integration of multi-omics was performed to elucidate the toxicity mechanism involved in developmental neurotoxicity. In a concentration-dependent manner, exposure to PFOS provoked hyperactivity and hypoactivity under light and dark conditions, respectively. Individual omics revealed that PFOS exposure caused perturbations in the pathways of neurological function, oxidative stress, and energy metabolism. Integrated omics implied that there were decisive pathways for axonal deformation, neuroinflammatory stimulation, and dysregulation of calcium ion signaling, which are more clearly specified for neurotoxicity. Overall, our findings broaden the molecular understanding of the developmental neurotoxicity of PFOS, for which multi-omics and integrated omics analyses are efficient for discovering the significant molecular pathways related to developmental neurotoxicity in zebrafish.
2023-04-04 | GSE228664 | GEO
Project description:ZnO nanoparticles (NPs) are widely used in industrial and consumer products. Thus, understanding their interaction with biological systems is the key for their safe application. The aim of present study was to evaluate the toxicological effects on the intestine of common carp, Cyprinus carpio, after dietary exposure to ZnO NPs. To assess the toxicity of ZnO NPs and of their toxic mechanism to gastrointestinal tract, we applied label free protein quantification on carp intestine considering the fact that fish are on the top of food chain in aquatic ecosystems. Even though carp and zebrafish do not have five intestinal segments like mammals (Brugman, 2016), previous studies have revealed that intestinal anatomy and architecture in cyprinid teleost fish is closely related to mammals with functional homology (Curry, 1939). Therefore, the findings can also provide beneficial information to understand the mechanisms underlying NPs toxicity in mammals.
2017-09-25 | PXD006867 | Pride
Project description:This series was used for two studies: Study 1: Recently it was discovered that the perfluorooctane sulfonate (PFOS) detected in wildlife, such as fish-eating birds, had a greater proportion of linear PFOS (L-PFOS) than the manufactured technical product (T-PFOS), which contains linear and branched isomers. This suggests toxicological studies based on T-PFOS data may inaccurately assess exposure risk to wildlife. To determine if PFOS effects were influenced by isomer content we compared the transcriptional profiles of cultured chicken embryonic hepatocytes (CEH) exposed to either L-PFOS or T-PFOS using Agilent microarrays. At equal concentrations (10 ?M), T-PFOS altered the expression of more transcripts (340, >1.5 fold change, p<0.05) compared to L-PFOS (130 transcripts). Higher concentrations of L-PFOS (40 ?M) were also less transcriptionally disruptive (217 transcripts) than T-PFOS at 10 ?M. Functional analysis showed that L-PFOS and T-PFOS affected genes involved in lipid metabolism, hepatic system development and cellular growth and proliferation. Pathway and interactome analysis suggested that genes may be affected through the RXR receptor, oxidative stress response, TP53 signaling, MYC signaling, Wnt/?-catenin signaling and PPAR? and SREBP receptors. In all functional categories and pathways examined, the response elicited by T-PFOS was greater than L-PFOS. These data show that T-PFOS elicits a greater transcriptional response in CEH than L-PFOS alone and demonstrates the importance of considering the isomer-specific toxicological properties of PFOS when assessing exposure risk. Study 2: In many bird populations, concentrations of perfluoroundanoic acid (PFUdA) are second only to perfluorooctane sulfonate (PFOS) among perfluoroalkyl compounds. Here, we used microarrays to characterize the transcriptional response of cultured chicken embryonic hepatocytes (CEH) to PFUdA and compared it to the response induced by PFOS. At non-cytotoxic doses, PFUdA (1 or 10 ?M) disrupted the expression of more genes (854) than PFOS (447, at 10 or 40 ?M) in CEH. Using functional, pathway and interactome analysis we identified several potentially important modes-of-action (MoAs) for PFUdA and some associated key events, including the suppression of the acute-phase response (APR) through peroxisome proliferator activated receptor activation. We then measured the expression of five APR genes, fibrinogen alpha (fga), fibrinogen gamma (fgg), thrombin (f2), plasminogen (plg), and protein C (proC), in the liver of chicken embryos exposed in ovo to PFUdA. The expression of fga, f2, and proC were down-regulated in embryo livers (100 or 1000 ng/g, p<0.1) as predicted from microarray analysis, whereas fibrinogen gamma (fgg) was up-regulated and plg was not significantly affected. Our results demonstrate PFUdA is more transcriptionally disruptive than PFOS in CEH. Additionally, we identified APR suppression as a potentially important and environmentally relevant MoA. These findings suggest in ovo exposure of birds to PFUdA could lead to post-hatch developmental deficiencies, such as impaired immune response.
2011-10-29 | GSE33291 | GEO