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Microbiota colonization status influences developmental toxicity of bisphenol A in embryonic zebrafish
Citation:
Tal, T., D. Betancourt, D. Hunter, S. Espenschied, J. Rawls, S. Charla, T. Dean, AND C. Wood. Microbiota colonization status influences developmental toxicity of bisphenol A in embryonic zebrafish. Society of Toxicology, New Orleans, LA, March 13 - 17, 2016.
Impact/Purpose:
There is growing evidence that the microbiome 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 embryonic zebrafish to explore whether chemical-induced developmental toxicity outcomes are sensitive to colonization status. These data show that normal microbiota are capable of shifting the chemical potency of BPA during development.
Description:
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 the presence or absence of microbiota. 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.