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Examining the interaction between developmental toxicity and microbiota colonization
Tal, T., D. Betancourt, D. Phelps, D. Hunter, S. Espenschied, J. Rawls, S. Ferguson, AND C. Wood. Examining the interaction between developmental toxicity and microbiota colonization. 2016 Duke Zebrafish Symposium, Durham, NC, March 03, 2016.
It is not well understood whether microbiota modify chemical toxicity. This research outlines the development of a model system to test whether the developmental toxicity of environmental chemicals is modifiable by colonization status in zebrafish.
There is growing evidence that microbiota can modify the toxicokinetics and/or toxicodynamics of environmental chemicals. Commonly used mammalian systems have limited ability to link phenotypic effects in exposed animals to colonization status. Here, we used gnotobiotic zebrafish to explore whether chemical-induced developmental toxicity outcomes are sensitive to colonization status. Gnotobiotic zebrafish were generated at 0 days post fertilization (dpf). At 1 dpf, culture sterility was assessed and a subset of gnotobiotic zebrafish were colonized with complex microbiota harvested from a conventional zebrafish aquaculture facility. Gnotobiotic and conventionalized cohorts were statically exposed to 1, 10, 40, or 100 uM bisphenol A (BPA) or 0.4% DMSO from 1-6 dpf. Culture sterility, developmental toxicity, and neurobehavioral development using a standard locomotor assay consisting of alternating light and dark periods, were assessed at 6 dpf. No differences in overt developmental toxicity were observed among BPA-exposed gnotobiotic and conventionalized zebrafish. Significant mortality occurred at > 40 uM BPA, regardless of microbial colonization. With regard to neurobehavioral development, there were no differences in mean movement during light or dark periods in gnotobiotic and conventionalized vehicle control larvae. Significant hypoactivity in the dark epoch was observed in gnotobiotic and conventionalized zebrafish exposed to 10 uM BPA relative to vehicle controls. A significant interaction between colonization status and exposure group was also noted, reflecting hyperactivity in gnotobiotic versus conventionalized zebrafish exposed to 1 uM BPA. These data show that normal microbiota are capable of shifting the chemical potency of BPA during development. This abstract does not necessarily reflect EPA policy.
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
INTEGRATED SYSTEMS TOXICOLOGY DIVISION
SYSTEMS BIOLOGY BRANCH