In Ovo Exposure of Mallard Ducks to Emerging PFAS
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PROVIDER: PRJEB70938 | ENA |
REPOSITORIES: ENA
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Project description:Background: Previous epidemiological studies have repeatedly found per- and polyfluoroalkyl substances (PFAS) exposure associated with higher circulating cholesterol, one of the greatest risk factors for development of coronary artery disease. The main route of cholesterol catabolism is through its conversion to bile acids, which circulate between the liver and ileum via enterohepatic circulation. Patients with coronary artery disease have decreased bile acid excretion, indicating that PFAS-induced changes of enterohepatic circulation may play a critical role in cardiovascular risk. Objectives: Using a mouse model with high LDL-VLDL cholesterol and aortic lesion development similar to humans, the current study investigates mechanisms linking exposure to a PFAS mixture with increased cholesterol. Methods: Male and female Ldlr-/- mice were fed an atherogenic diet (Clinton/Cybulsky low fat, 0.15% cholesterol) and exposed to a mixture of 5 PFAS representing legacy, replacement, and emerging subtypes (i.e., PFOA, PFOS, PFNA, PFHxS, GenX), each at a concentration of 2 mg/L, for 7 weeks. Blood was collected longitudinally for cholesterol measurements and mass spectrometry was used to measure circulating and fecal bile acids. Transcriptomic analysis of ileal samples was performed via RNA-sequencing. Results: After 7 weeks of PFAS exposure, average circulating PFAS levels were measured at 21.6, 20.1, 31.2, 23.5, and 1.5 µg/mL in PFAS-exposed females and 12.9, 9.7, 23, 14.3, and 1.7 µg/mL in PFAS-exposed males for PFOA, PFOS, PFHxS, PFNA, and GenX, respectively. PFAS exposure led to elevated circulating cholesterol levels after 7 weeks compared to vehicle mice, with females increasing 18% and males increasing 24%. Total circulating bile acid levels were elevated in PFAS-exposed mice by 230% in males and 290% in females compared to vehicle. PFAS decreased fecal bile acid levels by 62% in females and 59% in males. In the ileum, expression levels of the bile acid reuptake transporter ASBT were increased due to PFAS exposure. Discussion: Mice exposed to a PFAS mixture display increased circulating cholesterol and bile acids perhaps due to changes in enterohepatic circulation. This study implicates PFAS-mediated effects at the site of the ileum as a possible critical mediator of increased cardiovascular risk due to PFAS.
2024-08-14 | GSE263158 | GEO
Project description:Per- and polyfluoroalkyl substances (PFAS) are environmental contaminants of concern due to their persistence and potential adverse health effects. Epidemiological studies have linked PFAS with an increased risk of uterine diseases including fibroids however, the mechanisms involved remain to be elucidated. This study investigated the effects of individual PFAS, including long-chain “legacy” PFAS [perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS)] and short-chain “alternative” PFAS compounds [undecafluoro-2-methyl-3-oxahexanoic acid (GENX/HFPO-DA), perfluorobutanesulfonic acid (PFBS)], as well as a mixture of these chemicals on the function and transcriptome of an immortalized human myometrial cell line (UT-TERT). UT-TERT cells exposed to individual PFAS displayed increased cell viability and proliferation. Flow cytometry analysis revealed that PFOS and the PFAS mixture altered cell cycle progression. Migration assays demonstrated that PFOS and the PFAS mixture significantly enhanced UT-TERT cell migration. Gap junction intercellular communication (GJIC) was impaired following PFOA, PFBS, and PFAS mixture exposure, indicating potential disruptions in cell-to-cell communication within the uterine environment. Transcriptomic analysis using RNA-seq identified substantial changes in gene expression after exposure to environmentally relevant levels of individual PFAS and PFAS mixture. Pathway analysis revealed common molecular pathways associated with PFAS exposure, including Cell-to-Cell Signaling, Lipid Metabolism, and Cell Death and Survival, while other pathways were unique to specific PFAS. These findings highlight the multifaceted effects of PFAS on myometrial cells, providing insights into the potential mechanisms underlying PFAS-associated health risks. Further research is necessary to elucidate the long-term implications of PFAS exposure on uterine function and overall reproductive health.
2024-10-18 | GSE279836 | GEO
Project description:Using RNA-seq analysis, we have described in ovo liver cancer models providing the information that could help in preclinical research of new therapies for liver cancer.
2024-10-01 | GSE262490 | GEO
Project description:Abdominal fat deposition is an important trait in meat-producing ducks. F2 generations of 304 Cherry Valley and Runzhou Crested White ducks were studied to identify genes and lncRNAs affecting abdominal fat deposition. RNA sequencing was used to study abdominal fat tissue of four ducks each with high or low abdominal fat rates. In all, 336 upregulated and 297 downregu-lated mRNAs, and 95 upregulated and 119 downregulated lncRNAs were identified. Target gene prediction of differentially expressed lncRNAs identified 602 genes that were further subjected to Gene Ontology and KEGG pathway analysis. The target genes were enriched in pathways associ-ated with fat synthesis and metabolism and participated in biological processes, including Linoleic acid metabolism, lipid storage, and fat cell differentiation, indicating that these lncRNAs play an important role in abdominal fat deposition. This study lays foundations for exploring molecu-lar mechanisms underlying the regulation of abdominal fat deposition in ducks and provides a theoretical basis for breeding high-quality meat-producing ducks.
2022-05-19 | GSE203108 | GEO
Project description:Per- and polyfluoroalkyl Substances (PFAS) – the so-called ‘forever chemicals’ – are a major cause of environmental and health concern due to their toxicity and long-term persistence1,2. Yet, no efficient mechanisms for their removal have been identified. Here we report bioaccumulation of PFAS by several gut bacterial species over a wide range of concentrations from nanomolar up to 500 μM. For bioaccumulating Bacteroides uniformis, a highly prevalent species, we estimate intracellular PFAS concentration in the mM range – above that of most native metabolites. Despite this high bioaccumulation, B. uniformis cells could grow appreciably up to 250 μM perfluorononanoic acid (PFNA) exposure. Escherichia coli, which accumulated PFAS to a much lesser extent, substantially increased PFAS bioaccumulation when lacking TolC efflux pump indicating trans-membrane transport in PFAS bioaccumulation. Electron microscopy and cryogenic Focused Ion Beam-Secondary Ion Massspectrometry revealed distinct morphological changes and intracellular localisation of PFNA aggregates. Bioaccumulation of PFAS and transmembrane transport is also evident in proteomics, metabolomics, thermal proteome profiling, and mutations following adaptive laboratory evolution. In an in vivo context, mice colonized with human gut bacteria showed, compared to germ-free controls or those colonized with low-bioaccumulating bacteria, higher PFNA levels in excreted feces. As the gut microbiota is a critical interface between exposure and human body, our results have implications for understanding and utilizing microbial contribution to PFAS clearance.
2025-04-28 | PXD062206 | Pride
Project description:The placenta is crucial for fetal development, is affected by PFAS toxicity, and evidence is accumulating that gestational PFAS perturb the epigenetic activity of the placenta. Gestational PFAS exposure can adversely affect offspring, yet individual and cumulative impacts of PFAS on the placental epigenome remain underexplored. Here, we conducted an epigenome-wide association study (EWAS) to examine the relationships between placental PFAS levels and DNA methylation in a cohort of mother-infant dyads in Arkansas (N = 151). We measured 17 PFAS in human placental tissues and quantified placental DNA methylation levels via the Illumina EPIC Microarray. We tested for differential DNA methylation with individual PFAS, and with mixtures of multiple PFAS. Our results demonstrated that numerous epigenetic loci were perturbed by PFAS, with PFHxS exhibiting the most abundant effects. Mixture analyses suggested cumulative effects of PFOA and PFOS, while PFHxS may act more independently. We additionally explored whether sex-specific effects may be present and concluded that future large studies should explicitly test for sex-specific effects. The genes that are annotated to our PFAS-associated epigenetic loci are primarily involved in growth processes and cardiometabolic health, while some genes are involved in neurodevelopment. These findings shed light on how prenatal PFAS exposures affect birth outcomes and children's health, emphasizing the importance of understanding PFAS mechanisms in the in-utero environment.
2025-01-29 | GSE288358 | GEO
Project description:Gut Virome of Domestic Ducks (Anas platyrhynchos)
| PRJNA302767 | ENA
Project description:The per-and polyfluoroalkyl substances (PFAS) are of significant global concern due to their highly ubiquitous and persistent nature, bioaccumulation in organisms, and potential toxicity. The aquatic environment is known as an important sink for PFAS resulting in high concentrations in aquatic organisms. However, little is known about the developmental windows of sensitivity in which the PFAS chemicals are biologically active, in addition to the toxicity endpoints that best reflect chemical hazard. In this study, zebrafish (Danio rerio) were exposed to a 0.33% DMSO vehicle control, 1uM chlorpyrifos (CAS 2921-88-2) positive control, and eight concentrations (0-100 uM, half-log dilutions) of three environmentally relevant PFAS compounds in concentration-response: PFOS (CAS 1763-21-1), PFOA (CAS 45285-51-6), and PFHxS (CAS 355-46-4). There was also a group of unexposed zebrafish aliquoted from a single pool into all exposure plates to serve as a quality assurance measure. The goal of this study was to generate transcriptomic point of departure (tPOD; a benchmark dose/concentration -based treatment level below which a concerted gene expression response is not observed) estimates for zebrafish exposed to PFAS compounds as a health protective exposure level for risk assessment. Through the use of short-term embryo/larval plate-based high-throughput toxicity tests, tPODs were determined across seven distinct developmental windows (6-24 hours post fertilization (hpf), 6-48 hpf, 24-48 hpf, 6-120 hpf, 24-120 hpf, 48-120 hpf, 96-120 hpf) to assess how common experimental design variables (e.g., different exposure durations, exposure at different developmental stages) affect point of departure estimates.
2024-08-28 | GSE242402 | GEO
Project description:Per- and polyfluoroalkyl substances (PFAS) are a very large (thousands of chemicals) category; these substances have important industrial and consumer product applications. PFAS are highly persistent in the environment, and some are known to pose human health hazard. Regulatory agencies worldwide are considering restrictions and outright bans of PFAS; however, little data exists to make informed decisions. Therefore, a prioritization strategy is urgently needed for evaluation of potential hazards of PFAS. Structure-based grouping could expedite selection of PFAS for testing; still, the hypothesis that structure-effect relationships exist requires confirmation. We tested 26 structurally diverse PFAS from 8 groups in two human cell types from organs that are thought to be targets for PFAS. We used human induced pluripotent stem cell-derived hepatocytes and cardiomyocytes and tested concentration-response effects on both cell function and gene expression. Few phenotypic effects were observed in hepatocytes, but negative chronotropy was observed for 8 of 26 PFAS. Substance- and cell-dependent transcriptomic changes were more pronounced; however, little evidence of group-specific effects was observed. In hepatocytes, we found up-regulation of stress-related and extracellular matrix organization pathways, and down-regulation of fat metabolism. In cardiomyocytes, contractility-related pathways were most affected. Using these data, we derived phenotypic and transcriptomic point of departure estimates and compared them to predicted PFAS exposures. The conservative estimates for bioactivity and exposure were used to derive margin-of-exposure (MOE) for each PFAS. We found that most (23 of 26) PFAS had MOE>1. Overall, our data suggests that chemical structure-based grouping of PFAS may not be an appropriate strategy to predict their biological effects. This means that testing of the individual PFAS would be needed for confident decision-making. Our proposed strategy of using two human cell types and considering both phenotypic and transcriptomic effects, combined with dose-response analysis, may be used for prioritization of PFAS.
2024-02-27 | GSE244107 | GEO