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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Oct 01, 2010 |
| Title |
Expression data from wild-type and PPARalpha-null mice exposed to perfluorooctane sulfonate (PFOS) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Perfluorooctane sulfonate (PFOS) is a perfluoroalkyl acid (PFAA) and a persistent environmental contaminant found in the tissues of humans and wildlife. Although blood levels of PFOS have begun to decline, health concerns remain because of the long half-life of PFOS in humans. Like other PFAAs, such as perfluorooctanoic acid (PFOA), PFOS is an activator of peroxisome proliferator-activated receptor-alpha (PPARα) and exhibits hepatocarcinogenic potential in rodents. PFOS is also a developmental toxicant in rodents where, unlike PFOA, it’s mode of action is independent of PPARα. Wild-type (WT) and PPARα-null (Null) mice were dosed with 0, 3, or 10 mg/kg/day PFOS for 7 days. Animals were euthanized, livers weighed, and liver samples collected for histology and preparation of total RNA. Gene profiling was conducted using Affymetrix 430_2 microarrays. In WT mice, PFOS induced changes that were characteristic of PPARα transactivation including regulation of genes associated with lipid metabolism, peroxisome biogenesis, proteasome activation, and inflammation. PPARα-independent changes were indicated in both WT and Null mice by altered expression of genes related to lipid metabolism, inflammation, and xenobiotic metabolism. Such results are similar to prior studies done with PFOA and are consistent with modest activation of the constitutive androstane receptor (CAR) and possibly PPARγ and/or PPARβ/δ. Unique treatment-related effects were also found in Null mice including altered expression of genes associated with ribosome biogenesis, oxidative phosphorylation and cholesterol biosynthesis. Of interest was up-regulation of Cyp7a1, a gene which is under the control of various transcription regulators. Hence, in addition to its ability to modestly activate PPARα, PFOS induces a variety of “off-target” effects as well.
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| Overall design |
PPARalpha-null and wild-type male mice at 6-9 months of age were dosed by gavage for 7 consecutive days with either 0, 3, or 10 mg/kg PFOS (potassium salt) in 0.5% Tween 20. Five biological replicates consisting of individual animals were included in each dosage group. Data were compared to results previously published by our group for PFOA and Wy-14,643, a commonly used agonist of PPARalpha (Rosen et al., Toxicol Pathol. 36:592-607, 2008; GSE9796)
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| Contributor(s) |
Rosen MB, Schmid JR, Corton JC, Zehr RD, Das KP, Abbott BD, Lau C |
| Citation(s) |
20936131 |
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| Submission date |
Jul 09, 2010 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Mitchell B Rosen |
| E-mail(s) |
[email protected]
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| Phone |
919-541-2223
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| Fax |
919-541-4017
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| Organization name |
U.S. EPA
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| Department |
Reproductive Toxicology
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| Lab |
GEEBB
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| Street address |
2525 Hwy 54
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| City |
Research Triangle Park |
| State/province |
NC |
| ZIP/Postal code |
27711 |
| Country |
USA |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (30)
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| GSM565106 |
PPARalpha-null mouse + 0mg/kg PFOS, biological rep1 |
| GSM565107 |
PPARalpha-null mouse + 0mg/kg PFOS, biological rep2 |
| GSM565108 |
PPARalpha-null mouse + 0mg/kg PFOS, biological rep3 |
| GSM565109 |
PPARalpha-null mouse + 0mg/kg PFOS, biological rep4 |
| GSM565110 |
PPARalpha-null mouse + 0mg/kg PFOS, biological rep5 |
| GSM565111 |
PPARalpha-null mouse + 3mg/kg PFOS, biological rep1 |
| GSM565112 |
PPARalpha-null mouse + 3mg/kg PFOS, biological rep2 |
| GSM565113 |
PPARalpha-null mouse + 3mg/kg PFOS, biological rep3 |
| GSM565114 |
PPARalpha-null mouse + 3mg/kg PFOS, biological rep4 |
| GSM565115 |
PPARalpha-null mouse + 3mg/kg PFOS, biological rep5 |
| GSM565116 |
PPARalpha-null mouse +10mg/kg PFOS, biological rep1 |
| GSM565117 |
PPARalpha-null mouse +10mg/kg PFOS, biological rep2 |
| GSM565118 |
PPARalpha-null mouse +10mg/kg PFOS, biological rep3 |
| GSM565119 |
PPARalpha-null mouse +10mg/kg PFOS, biological rep4 |
| GSM565120 |
PPARalpha-null mouse +10mg/kg PFOS, biological rep5 |
| GSM565121 |
wild-type mouse + 0mg/kg PFOS, biological rep1 |
| GSM565122 |
wild-type mouse + 0mg/kg PFOS, biological rep2 |
| GSM565123 |
wild-type mouse + 0mg/kg PFOS, biological rep3 |
| GSM565124 |
wild-type mouse + 0mg/kg PFOS, biological rep4 |
| GSM565125 |
wild-type mouse + 0mg/kg PFOS, biological rep5 |
| GSM565126 |
wild-type mouse + 3mg/kg PFOS, biological rep1 |
| GSM565127 |
wild-type mouse + 3mg/kg PFOS, biological rep2 |
| GSM565128 |
wild-type mouse + 3mg/kg PFOS, biological rep3 |
| GSM565129 |
wild-type mouse + 3mg/kg PFOS, biological rep4 |
| GSM565130 |
wild-type mouse + 3mg/kg PFOS, biological rep5 |
| GSM565131 |
wild-type mouse + 10mg/kg PFOS, biological rep1 |
| GSM565132 |
wild-type mouse + 10mg/kg PFOS, biological rep2 |
| GSM565133 |
wild-type mouse +10mg/kg PFOS, biological rep3 |
| GSM565134 |
wild-type mouse + 10mg/kg PFOS, biological rep4 |
| GSM565135 |
wild-type mouse + 10mg/kg PFOS, biological rep5 |
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| Relations |
| BioProject |
PRJNA128117 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE22871_RAW.tar |
104.9 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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