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Global Gene Expression Analysis Using a Zebrafish Oligonucleotide Microarray Platform
Published on: August 10, 2009
Hepatic gene expression profiling using GeneChips in zebrafish exposed to 17alpha-methyldihydrotestosterone
J L Hoffmann1, R G Thomason, D M Lee
1Miami Valley Innovation Center, The Procter and Gamble Company, P.O. Box 538707, Cincinnati, OH 45253-8707, United States.
Aquatic Toxicology (Amsterdam, Netherlands)
|March 15, 2008
Summary
Exposure to the model androgen 17alpha-methyldihydrotestosterone (MDHT) altered hepatic gene expression and plasma hormone levels in female zebrafish. These findings identify potential biomarkers for detecting androgenic endocrine-disrupting chemicals (EDCs).
Area of Science:
- Environmental Toxicology
- Molecular Biology
- Endocrinology
Background:
- Androgenic compounds can disrupt normal physiological processes in aquatic organisms.
- Zebrafish (Danio rerio) are a valuable model for studying the effects of environmental contaminants.
- Understanding gene expression changes is crucial for assessing the impact of endocrine-disrupting chemicals (EDCs).
Purpose of the Study:
- To investigate the concentration- and time-dependent effects of 17alpha-methyldihydrotestosterone (MDHT) on hepatic gene expression in female zebrafish.
- To correlate gene expression changes with alterations in plasma steroid hormone levels and vitellogenin (VTG).
- To identify potential molecular biomarkers for detecting androgenic EDC exposure in fish.
Main Methods:
- Adult female zebrafish were exposed to varying concentrations of MDHT (0, 0.1, 0.7, 4.9 microg/L) for 24 and 168 hours.
- Hepatic gene expression was analyzed using custom Affymetrix GeneChip Zebrafish Genome Microarrays.
- Plasma levels of 17beta-estradiol (E2), testosterone (T), and VTG were measured using ELISA; body and ovary weights were also recorded.
Main Results:
- MDHT exposure significantly reduced E2 levels and increased T levels in a concentration-dependent manner.
- A significant number of genes (171 at 24h, 575 at 168h) were affected by MDHT exposure.
- Affected genes were involved in retinoic acid metabolism, steroid biosynthesis, hormone transport, and cell growth regulation.
Conclusions:
- MDHT exposure induces significant changes in hepatic gene expression and hormone profiles in female zebrafish.
- Identified genes related to steroid metabolism and hormone transport show promise as sensitive biomarkers for androgenic EDC exposure.
- These findings provide insights into the mode of action of potent androgens in female fish and aid in EDC screening.
