Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Blood transcriptome responses to PFOA and GenX treatment in the marsupial biomedical model Monodelphis domestica

ABSTRACT: The objective of our study is to investigate the effect of PFOA and GenX on the gene expression levels in Monodelphis domestica whole blood cultures by RNA-seq and identify the major susceptible genes. We identified 578 differentially expressed genes (DEGs) in the PFOA treatment group and 148 DEGs in the GenX treatment group. 10 genes were selected for qRT-PCR validation and were confirmed to be DEGs. Pathway enrichment analysis revealed that several developmental processes were altered after PFOA exposure and showed an up-regulated pattern. And down-regulated DEGs after PFOA exposure were enriched for metabolic process and immune system process. GenX exposure is associated with up-regulated fatty acid transport pathways and inflammatory process. Our study is the first one to investigate the effects of PFASs on marsupial animals, providing supportive evidence of the similar transcriptomic alterations caused by PFOA and a fluorinated alternative GenX, which can work as a complement of the previous studies of PFASs effects on rodent or human.

ORGANISM(S): Monodelphis domestica

PROVIDER: GSE208237 | GEO | 2022/10/15

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Transcriptional profilling of liver from C57BL/6 wildtype and PPARα-knockout mice treated with PFOA and GenX after 20 weeks of high-fat diet

Project description:Perfluoroalkyl substances (PFAS) are man-made chemicals with suspected endocrine-disrupting properties. Exposure to perfluorooctanoic acid (PFOA) has been linked to disturbed metabolism via the liver, although the exact mechanism is not clear. Moreover, information on the metabolic effects of the new PFAS alternative GenX is limited. We tested whether low-dose exposure to PFOA and GenX induces metabolic disturbances, including NAFLD, dyslipidemia, and glucose tolerance in mice and studied the involvement of PPARα. To this end, male C57BL/6J wildtype and PPARα−/− mice were given 0.05 or 0.3 mg/kg bw/day PFOA, or 0.3 mg/kg bw/day GenX next to a high-fat diet for 20 weeks. RNA sequencing was performed on liver, next to thorough assesment of metabolic parameters. RNA sequencing revealed that whereas the effects of GenX are entirely dependent on PPARα, effects of PFOA are mostly dependent on PPARα. In the absence of PPARα, the involvement of PXR/CAR becomes more prominent. Exposure to high-dose PFOA in mice decreased body weights and increased liver weights in wildtype and PPARα−/− mice. High-dose but not low-dose PFOA reduced plasma triglycerides and cholesterol, which for triglycerides, showed PPARα dependency. PFOA and GenX increased hepatic triglycerides in a PPARα-dependent manner. Overall, we show that long-term and low-dose exposure to PFOA and GenX disrupts lipid metabolism in mice. Whereas the effects of PFOA are mediated by multiple nuclear receptors, effects of GenX are entirely mediated by PPARα. Our data underscore the potential of PFAS to disrupt metabolism by altering signaling pathways in the liver.

2022-09-02 | GSE212294 | GEO

Fetal and maternal liver expression post gestational exposure to perfluorooctanoic acid (PFOA) or hexafluoropropylene oxide-dimer acid (HFPO-DA or GenX) in CD-1 mice

Project description:Multiple per- and polyfluoroalkyl substances (PFAS) have been associated with adverse liver outcomes in adult humans and toxicological models, but effects on the developing liver or biologic pathways involved are not known. We performed whole-transcriptome gene expression analysis to investigate the molecular mechanisms of liver toxicity in the dam and female fetuses after exposure to two different PFAS, perfluorooctanoic acid (PFOA) and its replacement, hexafluoropropylene oxide-dimer acid (HFPO-DA, commonly referred to as GenX).

2022-11-29 | GSE199233 | GEO

Identifying Human Specific Adverse Outcome Pathways of Per- and Polyfluoroalkyl Substances Using Liver-Chimeric Humanized Mice

Project description:We investigated the effects of per- and polyfluroralkyl substance exposure on FRG liver-chimeric humanized mice on a C57Bl/6 background. These PFAS included PFOA, PFOS, and GenX. These mice were exposed to water ad libitum for 28 days to reach human relevant serum concentrations. We then performed RNA-Sequencing on isolated whole liver lysate to determine differentially expressed genes.

2023-07-14 | GSE208636 | GEO

Acute GenX exposure induces spinal deformations and arrhythmia, and alters expression of genes involved in cardiac, vascular, neural, and visual systems during zebrafish (Danio rerio) early development

Project description:This study assessed the potential for GenX exposure to exert adverse effects during early development of zebrafish using morphological and physiological assessments, and further performed gene expression analysis on sublethal exposures to evaluate the underlying toxicogenomics. Zebrafish embryos exposed to GenX concentrations of 0.5 – 20000 mg/L were assessed at 24, 48, and 72 hours post-fertilization (hpf) for morphology, physiology, and survival. Shallow RNA-sequencing analysis of 9465 transcripts identified 38 genes that were consistently differentially expressed at 0.5, 1, 2, and 10 mg/L GenX exposures (compared to control at 72 hpf). Downregulated genes are associated with neurotransmission (6 genes) and visual response (10 genes), and upregulated genes are expressed in or regulate the cardiovascular system (7 genes). Our results suggest acute adverse effects by the alternative PFAS, GenX, in early zebrafish development by altering expression of genes involved in or regulating the heart and vascular tissue, neurotransmission, and visual response.

2022-03-22 | GSE198976 | GEO

Replacement Per and Polyfluoroalkyl Substance GenX Induces Fibroinflammatory Gene Expression in Primary Human Hepatocytes

Project description:To goal of this study was to determine the effects of GenX on freshly isolated primary human hepatocytes (PHH).

2022-07-21 | GSE187633 | GEO

Expression data from Human bone mesenchymal stem cells

Project description:Analysis of Human bone mesenchymal stem cells treated separately with DMSO vehicle, 100 nM perfluorooctanesulfonat(PFOS), 100 nM perfluorooctanoic acid(PFOA), 100 nM perfluorohexanesulphonate(PFHxS) or100 nM Chlorinated polyfluoroalkyl ether sulfonate(F-53B) for 7 days. Results provide insight into the molecular mechanisms by which PFASs interfere with osteogenic differentiation potential in HBMSCs.

2019-12-31 | GSE115836 | GEO

Unveiling the molecular effects of replacement and legacy PFASs: Transcriptomic analysis of zebrafish embryos reveals surprising similarities and potencies

Project description:The prevalence of per- and poly-fluoroalkyl substances (PFASs) in humans, wildlife, and the environment has led to restrictions on certain legacy PFASs due to their recognized toxic effects. Consequently, alternative "replacement" PFASs have been introduced and are becoming increasingly prevalent in environmental matrices. Despite their perceived environmental relevance, few studies have investigated the molecular effects of both legacy and replacement PFASs under sub-lethal and short-term exposures. This study aimed to address this gap by utilizing next-generation transcriptomic sequencing to compare the molecular impacts of exposure to the legacy PFOS and two of its replacements, PFECHS and FBSA. Employing zebrafish embryos as an experimental model, the research assessed sub-lethal apical effects (mortality, morphology, and growth), identified differentially expressed genes (DEGs) and enriched pathways, and determined transcriptomic points of departure (tPoDs) for each compound individually. Results indicated that PFOS exhibited the highest relative potency, followed by PFECHS and then FBSA, as supported by derived tPoDs. While similarities were observed among the top 3,000 DEGs across all compounds, over-representation analysis revealed slight differences, with PFECHS and PFOS both affecting focal adhesion and ECM receptor activation, whereas FBSA uniquely influenced the steroid biosynthesis pathway. Notably, PFOS demonstrated the lowest tPoD identified to date, suggesting greater potency than previously quantified. These findings raise concerns regarding the safety of emerging replacement PFASs and challenge assumptions about PFAS toxicity solely resulting from their accumulative potential. As replacement PFASs continue to proliferate in the environment, this study underscores the need for heightened scrutiny of their effects and questions current regulatory thresholds.

2024-06-30 | GSE263667 | GEO

An X chromosome microRNA cluster in the marsupial species Monodelphis domestica.

Project description:MicroRNAs (miRNAs) are an important class of posttranscriptional gene expression regulators. In the course of mapping novel marsupial-specific miRNAs in the genome of the gray short-tailed opossum, Monodelphis domestica, we encountered a cluster of 39 actual and potential miRNAs spanning 102 kb of the X chromosome. Analysis of the cluster revealed that 37 of the 39 miRNAs are predicted to form thermodynamically stable hairpins, and at least 3 members have been directly cloned from M. domestica tissues. The sequence characteristics of these miRNAs suggest that they all descended from a single common ancestor. Further, 2 distinct families appear to have diversified from the ancestral sequence through different duplication mechanisms: one through a series of simple tandem duplications and the other through a recurrent transposon-mediated duplication process.

| S-EPMC3156565 | biostudies-literature

Convergent and divergent evolution of genomic imprinting in the marsupial Monodelphis domestica.

Project description:BackgroundGenomic imprinting is an epigenetic phenomenon resulting in parent-of-origin specific monoallelic gene expression. It is postulated to have evolved in placental mammals to modulate intrauterine resource allocation to the offspring. In this study, we determined the imprint status of metatherian orthologues of eutherian imprinted genes.ResultsL3MBTL and HTR2A were shown to be imprinted in Monodelphis domestica (the gray short-tailed opossum). MEST expressed a monoallelic and a biallelic transcript, as in eutherians. In contrast, IMPACT, COPG2, and PLAGL1 were not imprinted in the opossum. Differentially methylated regions (DMRs) involved in regulating imprinting in eutherians were not found at any of the new imprinted loci in the opossum. Interestingly, a novel DMR was identified in intron 11 of the imprinted IGF2R gene, but this was not conserved in eutherians. The promoter regions of the imprinted genes in the opossum were enriched for the activating histone modification H3 Lysine 4 dimethylation.ConclusionsThe phenomenon of genomic imprinting is conserved in Therians, but the marked difference in the number and location of imprinted genes and DMRs between metatherians and eutherians indicates that imprinting is not fully conserved between the two Therian infra-classes. The identification of a novel DMR at a non-conserved location as well as the first demonstration of histone modifications at imprinted loci in the opossum suggest that genomic imprinting may have evolved in a common ancestor of these two Therian infra-classes with subsequent divergence of regulatory mechanisms in the two lineages.

| S-EPMC3507640 | biostudies-literature

A VpreB3 homologue in a marsupial, the gray short-tailed opossum, Monodelphis domestica.

Project description:A VpreB surrogate light (SL) chain was identified for the first time in a marsupial, the opossum Monodelphis domestica. Comparing the opossum VpreB to homologues from eutherian (placental mammals) and avian species supported the marsupial gene being VpreB3. VpreB3 is a protein that is not known to traffic to the cell surface as part of the pre-B cell receptor. Rather, VpreB3 associates with nascent immunoglobulin chains in the endoplasmic reticulum. Homologues of other known SL chains VpreB1, VpreB2, and λ5, which are found in eutherian mammals, were not found in the opossum genome, nor have they been identified in the genomes of nonmammals. VpreB3 likely evolved from earlier gene duplication, independent of that which generated VpreB1 and VpreB2 in eutherians. The apparent absence of VpreB1, VpreB2, and λ5 in marsupials suggests that an extracellular pre-B cell receptor containing SL chains, as it has been defined in humans and mice, may be unique to eutherian mammals. In contrast, the conservation of VpreB3 in marsupials and its presence in nonmammals is consistent with previous hypotheses that it is playing a more primordial role in B cell development.

| S-EPMC3396720 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data