A Graphical Systems Model to Facilitate Hypothesis-Driven Ecotoxicogenomics Research on the Teleost Brain—Pituitary—Gonadal Axis.

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Title: A Graphical Systems Model to Facilitate Hypothesis-Driven Ecotoxicogenomics Research on the Teleost Brain—Pituitary—Gonadal Axis.
Authors: Villeneuve, Daniel L.1 villeneuve.dan@epa.gov, Larkin, Patrick2, Knoebl, Iris3, Miracle, Ann L.4, Kahl, Michael D.1, Jensen, Kathleen M.1, Makynen, Elizabeth A.1, Durhan, Elizabeth J.1, Carter, Barbara J.2, Denslow, Nancy D.5, Ankley, Gerald T.1
Source: Environmental Science & Technology. 1/1/2007, Vol. 41 Issue 1, p321-330. 10p. 1 Diagram, 2 Charts, 1 Graph.
Subjects: Pollution, Graphic methods, Messenger RNA, Oligonucleotides, DNA microarrays, Polymerase chain reaction, Fish research, Aromatase, Biochemistry
Abstract: Graphical systems models are powerful tools that can help facilitate hypothesis-driven ecotoxicogenomic research and aid in mechanistic interpretation of results. This paper describes a novel graphical model of the teleost brain-pituitary-gonadal (BPG) axis designed for ecotoxi-cogenomics research on endocrine-disrupting chemicals using small fish models. The model incorporates six compartments representing the major organs involved in the fish reproductive axis and depicts the interactions of over 105 proteins and 40 simple molecules, transcriptional regulation of 25 genes, and over 300 different reactions/processes. Application of the model is illustrated in the context of a study examining effects of the competitive aromatase inhibitor, fadrozole, on gene expression in gonad, brain, and liver tissue of fathead minnows. Changes in mRNA transcript abundance were measured using a fathead minnow oligonucleotide microarray and quantitative real-time polymerase chain reaction. Gene expression changes observed in the ovaries of females exposed to 6.3 μg fadrozole/L for 7 d were functionally consistent with fadrozole's mechanism of action, and expected compensatory responses of the BPG axis to fadrozole's effects. Furthermore, microarray results helped identify additional elements (genes/proteins) that could be included in the model to potentially increase its predictive capacity. With proper recognition of their utility and limitations, graphical models can serve as important tools for linking molecular and biochemical changes to whole organism outcomes. [ABSTRACT FROM AUTHOR]
Copyright of Environmental Science & Technology is the property of American Chemical Society and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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DbLabel: Engineering Source
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  Data: A Graphical Systems Model to Facilitate Hypothesis-Driven Ecotoxicogenomics Research on the Teleost Brain—Pituitary—Gonadal Axis.
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  Data: <searchLink fieldCode="AR" term="%22Villeneuve%2C+Daniel+L%2E%22">Villeneuve, Daniel L.</searchLink><relatesTo>1</relatesTo><i> villeneuve.dan@epa.gov</i><br /><searchLink fieldCode="AR" term="%22Larkin%2C+Patrick%22">Larkin, Patrick</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Knoebl%2C+Iris%22">Knoebl, Iris</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Miracle%2C+Ann+L%2E%22">Miracle, Ann L.</searchLink><relatesTo>4</relatesTo><br /><searchLink fieldCode="AR" term="%22Kahl%2C+Michael+D%2E%22">Kahl, Michael D.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Jensen%2C+Kathleen+M%2E%22">Jensen, Kathleen M.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Makynen%2C+Elizabeth+A%2E%22">Makynen, Elizabeth A.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Durhan%2C+Elizabeth+J%2E%22">Durhan, Elizabeth J.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Carter%2C+Barbara+J%2E%22">Carter, Barbara J.</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Denslow%2C+Nancy+D%2E%22">Denslow, Nancy D.</searchLink><relatesTo>5</relatesTo><br /><searchLink fieldCode="AR" term="%22Ankley%2C+Gerald+T%2E%22">Ankley, Gerald T.</searchLink><relatesTo>1</relatesTo>
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  Data: <searchLink fieldCode="JN" term="%22Environmental+Science+%26+Technology%22">Environmental Science & Technology</searchLink>. 1/1/2007, Vol. 41 Issue 1, p321-330. 10p. 1 Diagram, 2 Charts, 1 Graph.
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  Data: <searchLink fieldCode="DE" term="%22Pollution%22">Pollution</searchLink><br /><searchLink fieldCode="DE" term="%22Graphic+methods%22">Graphic methods</searchLink><br /><searchLink fieldCode="DE" term="%22Messenger+RNA%22">Messenger RNA</searchLink><br /><searchLink fieldCode="DE" term="%22Oligonucleotides%22">Oligonucleotides</searchLink><br /><searchLink fieldCode="DE" term="%22DNA+microarrays%22">DNA microarrays</searchLink><br /><searchLink fieldCode="DE" term="%22Polymerase+chain+reaction%22">Polymerase chain reaction</searchLink><br /><searchLink fieldCode="DE" term="%22Fish+research%22">Fish research</searchLink><br /><searchLink fieldCode="DE" term="%22Aromatase%22">Aromatase</searchLink><br /><searchLink fieldCode="DE" term="%22Biochemistry%22">Biochemistry</searchLink>
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  Label: Abstract
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  Data: Graphical systems models are powerful tools that can help facilitate hypothesis-driven ecotoxicogenomic research and aid in mechanistic interpretation of results. This paper describes a novel graphical model of the teleost brain-pituitary-gonadal (BPG) axis designed for ecotoxi-cogenomics research on endocrine-disrupting chemicals using small fish models. The model incorporates six compartments representing the major organs involved in the fish reproductive axis and depicts the interactions of over 105 proteins and 40 simple molecules, transcriptional regulation of 25 genes, and over 300 different reactions/processes. Application of the model is illustrated in the context of a study examining effects of the competitive aromatase inhibitor, fadrozole, on gene expression in gonad, brain, and liver tissue of fathead minnows. Changes in mRNA transcript abundance were measured using a fathead minnow oligonucleotide microarray and quantitative real-time polymerase chain reaction. Gene expression changes observed in the ovaries of females exposed to 6.3 μg fadrozole/L for 7 d were functionally consistent with fadrozole's mechanism of action, and expected compensatory responses of the BPG axis to fadrozole's effects. Furthermore, microarray results helped identify additional elements (genes/proteins) that could be included in the model to potentially increase its predictive capacity. With proper recognition of their utility and limitations, graphical models can serve as important tools for linking molecular and biochemical changes to whole organism outcomes. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
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  Data: <i>Copyright of Environmental Science & Technology is the property of American Chemical Society and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1021/es061739x
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        Text: English
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      – SubjectFull: Messenger RNA
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