Evidence map›Paper›PMID 28558994›Full record

ArticleToxicology2017

PPARα-independent transcriptional targets of perfluoroalkyl acids revealed by transcript profiling.

Mitchell B Rosen, Kaberi P Das, John Rooney, Barbara Abbott, Christopher Lau, J Christopher Corton

Abstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Toxicology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
109citing papers in PubMed, 1 pooled it
11.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

109 citing papers in PubMed, 1 synthesis or guideline pooled it, 205 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Developmental exposure to a PFAS mixture impairs the anamnestic response to influenza A virus infection in mice.Toxicological sciences : an official journal of the Society of Toxicology · 2026
    Article
  6. Article
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  8. Review
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  10. Article
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  12. Synergistic toxicity in alcohol-associated liver disease and PFAS exposure.Toxicological sciences : an official journal of the Society of Toxicology · 2025
    Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
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49 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Mitchell B RosenU.S. Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Integrated Systems Toxicology Division, USA. Electronic address: rosen.mitch@epa.gov.
Kaberi P DasToxicology Assessment Division, Research Triangle Park, NC, USA. Electronic address: das.kaberi@epa.gov.
John RooneyU.S. Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Integrated Systems Toxicology Division, USA. Electronic address: rooney.john@epa.gov.
Barbara AbbottToxicology Assessment Division, Research Triangle Park, NC, USA. Electronic address: abbott.barbara@epa.gov.
Christopher LauToxicology Assessment Division, Research Triangle Park, NC, USA. Electronic address: lau.christopher@epa.gov.
J Christopher CortonU.S. Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Integrated Systems Toxicology Division, USA. Electronic address: corton.chris@epa.gov.
Environmental Protection Agency · USResearch Triangle Park Foundation · US

Funding

Intramural EPA EPA999999
6 · The paper itself

Abstract

Perfluoroalkyl acids (PFAAs) are ubiquitous and persistent environmental contaminants. Compounds such as perfluoroocanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonate (PFHxS) are readily found in the tissues of humans and wildlife. While PFOA and PFOS have been the subject of numerous studies since they were first described over a decade ago, less is known about the biological activity of PFHxS and PFNA. Most PFAAs are activators of peroxisome proliferator-activated receptor α (PPARα), although the biological effects of these compounds are likely mediated by other factors in addition to PPARα. To evaluate the effects of PFHxS and PFNA, male wild-type and Pparα-null mice were dosed by oral gavage with PFHxS (3 or 10mg/kg/day), PFNA (1 or 3mg/kg/day), or vehicle for 7days, and liver gene expression was evaluated by full-genome microarrays. Gene expression patterns were then compared to historical in-house data for PFOA and PFOS in addition to the experimental hypolipidemic agent, WY-14,643. While WY-14,643 altered most genes in a PPARα-dependent manner, approximately 11-24% of regulated genes in PFAA-treated mice were independent of PPARα. The possibility that PFAAs regulate gene expression through other molecular pathways was evaluated. Using data available through a microarray database, PFAA gene expression profiles were found to exhibit significant similarity to profiles from mouse tissues exposed to agonists of the constitutive activated receptor (CAR), estrogen receptor α (ERα), and PPARγ. Human PPARγ and ERα were activated by all four PFAAs in trans-activation assays from the ToxCast screening program. Predictive gene expression biomarkers showed that PFAAs activate CAR in both genotypes and cause feminization of the liver transcriptome through suppression of signal transducer and activator of transcription 5B (STAT5B). These results indicate that, in addition to activating PPARα as a primary target, PFAAs also have the potential to activate CAR, PPARγ, and ERα as well as suppress STAT5B.

Indexed as

Oligonucleotide Array Sequence AnalysisAnimalsAnticholesteremic AgentsChemical and Drug Induced Liver InjuryComputational BiologyConstitutive Androstane ReceptorDatabases, GeneticEstrogen Receptor alphaEstrogensFatty AcidsFluorocarbonsGene Expression ProfilingGene Expression RegulationHepatomegalyHumansLiverAnticholesteremic AgentsConstitutive Androstane ReceptorESR1 protein, humanEstrogen Receptor alphaEstrogensFatty AcidsFluorocarbonsperfluorohexanesulfonic acidperfluoro-n-nonanoic acidpirinixic acidPPAR alphaPPAR gammaPyrimidinesReceptors, Cytoplasmic and NuclearSTAT5B protein, humanStat5b protein, mouseSTAT5 Transcription FactorSulfonic AcidsConstitutive activated receptorEstrogen receptor alphaLiverPerfluoroalkyl acidPeroxisome proliferator-activated receptor αPeroxisome proliferator-activated receptor γSTAT5BToxCastTranscript profiling

Identifiers

PMID28558994
PMCPMC6129013
OpenAlexW2618442397

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.