A graphical systems model to facilitate hypothesis-driven ecotoxicogenomics research on the teleost brain-pituitary-gonadal axis
Conceptual or graphical systems models are powerful tools that can help facilitate hypothesis-based ecotoxicogenomic research and aid mechanistic interpretation of toxicogenomic results. This paper presents a novel conceptual model of the teleost brain-pituitary-gonadal axis designed to aid ecotoxigenomics research on endocrine-disrupting chemicals using small fish models. Application of the model to toxicogenomics research was illustrated in the context of a recent study that examined the effects of the competitive aromatase inhibitor, fadrozole, on mRNA transcript abundance in gonad, brain, and liver tissue of exposed fathead minnows using a novel fathead minnow oligonucleotide microarray and quantitative real-time polymerase chain reaction. Changes in transcript abundance observed in the ovaries of females exposed to 6.3 ug 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, array results helped identify additional elements (genes/proteins) that could be included in the model to potentially increase it’s predictive capacity. However, model-based predictions did not readily explain the lack of differential mRNA expression (relative to controls) observed in the ovary of females exposed to 60 ug fadrozole/L for 7 d. Both the utility and limitations of conceptual systems models as tools for hypothesis-driven ecotoxicogenomics research are discussed.
- Research Organization:
- Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
- Sponsoring Organization:
- USDOE
- DOE Contract Number:
- AC05-76RL01830
- OSTI ID:
- 901178
- Report Number(s):
- PNNL-SA-52266; ESTHAG; TRN: US200713%%155
- Journal Information:
- Environmental Science & Technology, 41(1):321-330, Vol. 41, Issue 1; ISSN 0013-936X
- Country of Publication:
- United States
- Language:
- English
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