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HP4 Environmental Metabolomics
() High throughput metabolomic studies of developmental toxicity in Japanese medaka.
Viant, M1, Bundy, J2, Pincetich, C2, Tjeerdema, R2, 1 University of Birmingham, Birmingham, United Kingdom2 University of California, Davis, California, USA
ABSTRACT- Developing embryos can be particularly sensitive to toxic insult. To identify the biochemical mode of action and developmental stage at which toxicity occurs we require methods that can rapidly and inexpensively monitor the phenotypic changes during embryogenesis. 1H nuclear magnetic resonance (NMR) spectroscopy-based metabolomics affords several advantages for such a study including minimal sample preparation, high-throughput analyses, and unbiased detection of low molecular weight metabolites. We have investigated the metabolic changes occurring during normal development of Japanese medaka (Oryzias latipes) embryos. Several replicates at each of nine developmental stages were analyzed, covering the entire 8-day period of embryogenesis from fertilization to hatch. The 1H NMR spectra were processed and analyzed using principal components analysis enabling visualization of the biochemical changes that occur between each developmental stage. This illustrates our concept of a developmental trajectory through metabolic space, which summarizes the changes in the NMR-visible metabolome throughout embryogenesis. Recently we have exposed embryos to a series of trichloroethylene (TCE) concentrations, a ubiquitous groundwater contaminant that is of concern as a developmental toxicant. Following continuous TCE exposure throughout development, embryos were analyzed on day-7 of embryogenesis, and a dose dependent metabolic perturbation was observed along with metabolic biomarker profiles associated with TCE toxicity. We are currently analyzing the results from a further study in which the phenotype of control and TCE-exposed (6 ppm and 800 ppb) embryos were followed throughout the entire period of embryogenesis. These analyses, along with the normal developmental trajectories of medaka will be presented.
Key words: development, metabolomics, nmr, oryzias latipes
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