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Derivation and Evaluation of Putative Adverse Outcome Pathways for Effects of Cycylooxygenase inhibitors on Reproductive Processes in Female Fish

Published by U.S. EPA Office of Research and Development (ORD) | U.S. Environmental Protection Agency | Metadata Last Checked: August 02, 2025 | Last Modified: 2018-10-25
Fathead minnows (Pimephales promelas) were exposed to 100 ug/L indomethacin, 200 ug/L ibuprofen, or 20 ug/L celecoxib for 96 h. Effects on cycloxygenase enzyme activity in ovary, prostaglandin F2alpha concentrations in plasma, 17beta-estradiol concentrations in plasma, and vitellogenin concentrations in plasma were measured. Gene expression in ovary samples was evaluated using a 15,000 probe oligonucleotide microarray. Transcriptomics data (raw data and normalized) are available through the National Center for Biotechnology Information, Gene Expression Omnibus (GEO), accession number GSE72976. Metabolite profiles in liver tissue were measured by proton nuclear magnetic resonance. In addition to these data, the data set also contains identification of differentially expressed genes, pathway enrichment and gene set enrichment analyes, ToxCast data for indomethacin and celecoxib, chemical-gene interaction data derived from the Comparative Toxicogenomics database, and results from Level 1, Level 2, and Level 3 SeqAPASS analyses that examine conservation of target proteins across species (https://seqapass.epa.gov/seqapass/). This dataset is associated with the following publication: Martinovic-Weigelt, D., A. Mehinto, G. Ankley , J. Berninger, T. Collette , J. Davis , N. Denslow, E. Durhan, E. Eid, D. Ekman , K. Jensen , M. Kahl , C. LaLone , Q. Teng , and D. Villeneuve. Derivation and evaluation of putative adverse outcome pathways for the effects of cyclooxygenase inhibitors on reproductive processes in female fish. TOXICOLOGICAL SCIENCES. Society of Toxicology, 156(2): 344-361, (2017).

Resources

15 resources available

  • https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE72976

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  • 1 ORD-013745 Differentially expressed genes.xlsx

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  • 10 ORD-013745 SeqAPASS level 3, cox1.xlsx

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  • 11 ORD-013745 SeqAPASS level 3, cox2.xlsx

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  • 12 ORD-013745 MartinovicToxSCI_VTG_E2_COX_PGF.xlsx

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  • 13 ORD-013745 COX Inhib_Metabolomics_Diff Spec.xlsx

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  • 14 ORD-013745 COX Inhib_Metabolomics_PCA.xlsx

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  • 2 ORD-013745 Pathway enrichment and GSEA.xlsx

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  • 3 ORD-013745 Ingenuity Pathway Analyes.xlsx

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  • 4 ORD-013745 ToxCast data.xlsx

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  • 5 ORD-013745 CTD Chemical-gene interactions.xlsx

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  • 6 ORD-013745 SeqAPASS level 1, cox1.csv

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  • 7 ORD-013745 SeqAPASS level 1, cox2.csv

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  • 8 ORD-013745 SeqAPASS level 2, cox1.csv

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  • 9 ORD-013745 SeqAPASS level 2, cox2.csv

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Complete Metadata
accessLevel public
bureauCode 
                                            [
  "020:00"
]
contactPoint 
                                            {
  "fn": "Daniel Villeneuve",
  "hasEmail": "mailto:villeneuve.dan@epa.gov"
}
description Fathead minnows (Pimephales promelas) were exposed to 100 ug/L indomethacin, 200 ug/L ibuprofen, or 20 ug/L celecoxib for 96 h. Effects on cycloxygenase enzyme activity in ovary, prostaglandin F2alpha concentrations in plasma, 17beta-estradiol concentrations in plasma, and vitellogenin concentrations in plasma were measured. Gene expression in ovary samples was evaluated using a 15,000 probe oligonucleotide microarray. Transcriptomics data (raw data and normalized) are available through the National Center for Biotechnology Information, Gene Expression Omnibus (GEO), accession number GSE72976. Metabolite profiles in liver tissue were measured by proton nuclear magnetic resonance. In addition to these data, the data set also contains identification of differentially expressed genes, pathway enrichment and gene set enrichment analyes, ToxCast data for indomethacin and celecoxib, chemical-gene interaction data derived from the Comparative Toxicogenomics database, and results from Level 1, Level 2, and Level 3 SeqAPASS analyses that examine conservation of target proteins across species (https://seqapass.epa.gov/seqapass/). This dataset is associated with the following publication: Martinovic-Weigelt, D., A. Mehinto, G. Ankley , J. Berninger, T. Collette , J. Davis , N. Denslow, E. Durhan, E. Eid, D. Ekman , K. Jensen , M. Kahl , C. LaLone , Q. Teng , and D. Villeneuve. Derivation and evaluation of putative adverse outcome pathways for the effects of cyclooxygenase inhibitors on reproductive processes in female fish. TOXICOLOGICAL SCIENCES. Society of Toxicology, 156(2): 344-361, (2017).
distribution 
                                            [
  {
    "title": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE72976",
    "accessURL": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE72976"
  },
  {
    "title": "1 ORD-013745 Differentially expressed genes.xlsx",
    "mediaType": "application/vnd.openxmlformats-officedocument.spreadsheetml.sheet",
    "downloadURL": "https://pasteur.epa.gov/uploads/10.23719/1503124/1%20ORD-013745%20Differentially%20expressed%20genes.xlsx"
  },
  {
    "title": "10 ORD-013745 SeqAPASS level 3, cox1.xlsx",
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    "title": "11 ORD-013745 SeqAPASS level 3, cox2.xlsx",
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    "title": "12 ORD-013745 MartinovicToxSCI_VTG_E2_COX_PGF.xlsx",
    "mediaType": "application/vnd.openxmlformats-officedocument.spreadsheetml.sheet",
    "downloadURL": "https://pasteur.epa.gov/uploads/10.23719/1503124/12%20ORD-013745%20MartinovicToxSCI_VTG_E2_COX_PGF.xlsx"
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    "title": "13 ORD-013745 COX Inhib_Metabolomics_Diff Spec.xlsx",
    "mediaType": "application/vnd.openxmlformats-officedocument.spreadsheetml.sheet",
    "downloadURL": "https://pasteur.epa.gov/uploads/10.23719/1503124/13%20ORD-013745%20COX%20Inhib_Metabolomics_Diff%20Spec.xlsx"
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    "title": "14 ORD-013745 COX Inhib_Metabolomics_PCA.xlsx",
    "mediaType": "application/vnd.openxmlformats-officedocument.spreadsheetml.sheet",
    "downloadURL": "https://pasteur.epa.gov/uploads/10.23719/1503124/14%20ORD-013745%20COX%20Inhib_Metabolomics_PCA.xlsx"
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  {
    "title": "2 ORD-013745 Pathway enrichment and GSEA.xlsx",
    "mediaType": "application/vnd.openxmlformats-officedocument.spreadsheetml.sheet",
    "downloadURL": "https://pasteur.epa.gov/uploads/10.23719/1503124/2%20ORD-013745%20Pathway%20enrichment%20and%20GSEA.xlsx"
  },
  {
    "title": "3 ORD-013745 Ingenuity Pathway Analyes.xlsx",
    "mediaType": "application/vnd.openxmlformats-officedocument.spreadsheetml.sheet",
    "downloadURL": "https://pasteur.epa.gov/uploads/10.23719/1503124/3%20ORD-013745%20Ingenuity%20Pathway%20Analyes.xlsx"
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  {
    "title": "4 ORD-013745 ToxCast data.xlsx",
    "mediaType": "application/vnd.openxmlformats-officedocument.spreadsheetml.sheet",
    "downloadURL": "https://pasteur.epa.gov/uploads/10.23719/1503124/4%20ORD-013745%20ToxCast%20data.xlsx"
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  {
    "title": "5 ORD-013745 CTD Chemical-gene interactions.xlsx",
    "mediaType": "application/vnd.openxmlformats-officedocument.spreadsheetml.sheet",
    "downloadURL": "https://pasteur.epa.gov/uploads/10.23719/1503124/5%20ORD-013745%20CTD%20Chemical-gene%20interactions.xlsx"
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  {
    "title": "6 ORD-013745 SeqAPASS level 1, cox1.csv",
    "mediaType": "application/vnd.ms-excel",
    "downloadURL": "https://pasteur.epa.gov/uploads/10.23719/1503124/6%20ORD-013745%20SeqAPASS%20level%201%2C%20cox1.csv"
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  {
    "title": "7 ORD-013745 SeqAPASS level 1, cox2.csv",
    "mediaType": "application/vnd.ms-excel",
    "downloadURL": "https://pasteur.epa.gov/uploads/10.23719/1503124/7%20ORD-013745%20SeqAPASS%20level%201%2C%20cox2.csv"
  },
  {
    "title": "8 ORD-013745 SeqAPASS level 2, cox1.csv",
    "mediaType": "application/vnd.ms-excel",
    "downloadURL": "https://pasteur.epa.gov/uploads/10.23719/1503124/8%20ORD-013745%20SeqAPASS%20level%202%2C%20cox1.csv"
  },
  {
    "title": "9 ORD-013745 SeqAPASS level 2, cox2.csv",
    "mediaType": "application/vnd.ms-excel",
    "downloadURL": "https://pasteur.epa.gov/uploads/10.23719/1503124/9%20ORD-013745%20SeqAPASS%20level%202%2C%20cox2.csv"
  }
]
identifier https://doi.org/10.23719/1503124
keyword 
                                            [
  "adverse outcome pathway",
  "aquatic ecosystems",
  "ecotoxicology",
  "endocrine disruption",
  "screening and prioritization"
]
license https://pasteur.epa.gov/license/sciencehub-license.html
modified 2018-10-25
programCode 
                                            [
  "020:095"
]
publisher 
                                            {
  "name": "U.S. EPA Office of Research and Development (ORD)",
  "subOrganizationOf": {
    "name": "U.S. Environmental Protection Agency",
    "subOrganizationOf": {
      "name": "U.S. Government"
    }
  }
}
references 
                                            [
  "https://doi.org/10.1093/toxsci/kfw257"
]
rights 
                                            null
title Derivation and Evaluation of Putative Adverse Outcome Pathways for Effects of Cycylooxygenase inhibitors on Reproductive Processes in Female Fish

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