GEO series
Perfluorooctane sulfonate (PFOS) exposure and alcohol-associated liver disease severity in a mouse chronic-binge ethanol feeding model
GSE288842
Mus musculus (mouse)
RNA-seq (gene expression)
24 samples
Submitted 2025/06/27
Platform GPL24247
At a glance
RNA-seq (gene expression) · mouse · 24 samples
- What it is
- RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
- Organism
- Mus musculus (mouse)
- Samples
- 24 samples: 6 × Pair-fed Vehicle vs 6 × Pair-fed PFOS vs 6 × Ethanol-fed Vehicle vs 6 × Ethanol-fed PFOSGroups are read from the sample names, not from the paper. Check the list below.
- Data you can get
- A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
- Paper
- Perfluorooctane sulfonate exposure and alcohol-associated liver disease severity in a mouse chronic-binge ethanol feeding modelToxicological sciences : an official journal of the Society of Toxicology · 2025
Summary (written by the submitters)
Background: Exposure to pollutants including the ubiquitous ‘forever chemical’, Perfluorooctane sulfonate (PFOS) has increasingly been associated with metabolic dysfunction-associated steatotic liver disease (MASLD). Recent epidemiological evidence has identified associations between Per- and polyfluoroalkyl substances (PFAS) exposure and increased liver injury in alcohol consumers, suggesting potential interactions between these exposures.
Read the full summary ↓
However, the intersection of pollutant exposures and alcohol-associated liver disease (ALD) is not well studied. We hypothesize that pollutants may disrupt hepatic metabolism to modify ALD severity. Recently, we developed a two-hit (ethanol plus pollutant) mouse model, enabling testing of this hypothesis. Here, we elucidate the metabolic and disease-modifying effects of PFOS in this model. Methods: Male C57BL/6J mice were fed isocaloric control or 5% Ethanol (EtOH) Lieber-DeCarli diet for 15 days. From day 6 of feeding, mice were concurrently gavaged with 1 mg/kg PFOS or 2% tween-80 vehicle for 10 days, followed by a 5 g/kg EtOH binge dose and euthanized 5-6 hours later. Results: Approximately 60% of the administered PFOS dose accumulated in liver. PFOS exacerbated EtOH-induced hepatic steatosis and was associated by higher levels of plasma very low-density lipoprotein (vLDL) and alanine aminotransferase (ALT). PFOS upregulated hepatic ethanol-metabolizing enzymes and lowered blood alcohol levels. Ingenuity Pathway Analysis (IPA) Top Toxicity Functions/Lists associated with hepatic gene expression following PFOS co-exposure in EtOH-fed mice included: fatty acid metabolism and liver steatosis; nuclear receptor activation, cytochrome P450, and reactive oxygen species (ROS); apoptosis; liver fibrosis; and hepatocellular carcinoma (HCC). GO/KEGG analyses similarly revealed enrichment in fatty acid, xenobiotic, alcohol, or glutathione metabolic processes; and Peroxisome proliferator-activated receptor (PPAR) signaling. PFOS upregulated hepatic expression of several nuclear receptors (e.g., Pparα, Car, and Pxr) and their P450 target genes (e.g., Cyp4a10, Cyp2b10, and Cyp3a11) by RT-PCR or Western blot, confirming key IPA predictions. Conclusions: PFOS is a metabolism disrupting chemical that worsened ALD severity. PFOS activated hepatic nuclear receptors and enriched hepatic transcriptional pathways associated with steatosis, xenobiotic metabolism, oxidative stress, cell death, fibrosis, and HCC. These data demonstrate a novel mechanism whereby PFOS exacerbates ALD through coordinated dysregulation of lipid homeostasis and liver injury, potentially mediated by nuclear receptor activation. The identification of PFOS as an ALD risk modifier highlight the critical need to evaluate environmental pollutants as potential contributors to liver disease progression in vulnerable populations. More data are required on environmental pollution as a disease modifying factor in ALD.
Published in
Ekuban FA, Gripshover TC, Ames P et al.
· Toxicological sciences : an official journal of the Society of Toxicology 2025
· PMID 40347464
· doi:10.1093/toxsci/kfaf066
This dataset
Download · which file do I need?
Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.
1 · Just have a look
Processed table
The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.
2 · Re-analyse it
Supplementary files
The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE288842_RAW.tar (it can run to tens of gigabytes).
3 · Start from the raw reads
Raw sequencing reads
The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.
What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.
Also filed as BioProject PRJNA1219599 and SRA study SRP561787. Searching any of these in the dataset finder brings you back here.
Study design
6 × Pair-fed Vehicle vs 6 × Pair-fed PFOS vs 6 × Ethanol-fed Vehicle vs 6 × Ethanol-fed PFOS
Supports a between-group comparison across 24 samples.
How we read this: 4 replicated groups read from 24 sample titles; they account for 24 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.
Samples in this study
- GSM8776425 Pair-fed Vehicle replicate 1 Pair-fed Vehicle
- GSM8776426 Pair-fed Vehicle replicate 2 Pair-fed Vehicle
- GSM8776427 Pair-fed Vehicle replicate 3 Pair-fed Vehicle
- GSM8776428 Pair-fed Vehicle replicate 4 Pair-fed Vehicle
- GSM8776429 Pair-fed Vehicle replicate 5 Pair-fed Vehicle
- GSM8776430 Pair-fed Vehicle replicate 6 Pair-fed Vehicle
- GSM8776431 Pair-fed PFOS replicate 1 Pair-fed PFOS
- GSM8776432 Pair-fed PFOS replicate 2 Pair-fed PFOS
- GSM8776433 Pair-fed PFOS replicate 3 Pair-fed PFOS
- GSM8776434 Pair-fed PFOS replicate 4 Pair-fed PFOS
- GSM8776435 Pair-fed PFOS replicate 5 Pair-fed PFOS
- GSM8776436 Pair-fed PFOS replicate 6 Pair-fed PFOS
- GSM8776437 Ethanol-fed Vehicle replicate 1 Ethanol-fed Vehicle
- GSM8776438 Ethanol-fed Vehicle replicate 2 Ethanol-fed Vehicle
- GSM8776439 Ethanol-fed Vehicle replicate 3 Ethanol-fed Vehicle
- GSM8776440 Ethanol-fed Vehicle replicate 4 Ethanol-fed Vehicle
- GSM8776441 Ethanol-fed Vehicle replicate 5 Ethanol-fed Vehicle
- GSM8776442 Ethanol-fed Vehicle replicate 6 Ethanol-fed Vehicle
- GSM8776443 Ethanol-fed PFOS replicate 1 Ethanol-fed PFOS
- GSM8776444 Ethanol-fed PFOS replicate 2 Ethanol-fed PFOS
- GSM8776445 Ethanol-fed PFOS replicate 3 Ethanol-fed PFOS
- GSM8776446 Ethanol-fed PFOS replicate 4 Ethanol-fed PFOS
- GSM8776447 Ethanol-fed PFOS replicate 5 Ethanol-fed PFOS
- GSM8776448 Ethanol-fed PFOS replicate 6 Ethanol-fed PFOS
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Share this dataset
Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.