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Effects of Bisphenol A and replacement compounds on neurobehavioral development mediated by microbial colonization status in zebrafish larvae
Citation:
Catron, T., D. Phelps, S. Keely, N. Brinkman, E. Anneken, AND T. Tal. Effects of Bisphenol A and replacement compounds on neurobehavioral development mediated by microbial colonization status in zebrafish larvae. Cellular & Molecular Mechanisms of Toxicity (GRS and GRC), Andover, Proctor Academy, August 12 - 18, 2017.
Impact/Purpose:
Intestinal microbes are thought to influence mood, anxiety, and increasingly, brain development. It is currently unknown whether and how microbiota might influence the developmental neurotoxicity of environmental chemicals although it has been proposed that intestinal microbiota may mediate developmental neurotoxicity effects of environmental chemicals either by performing biotransformations or serving as a target of chemical exposures. This work shows that exposure to the widespread environmental contaminant Bisphenol A (BPA) causes behavioral hypoactivity in the light in zebrafish larvae that contain microbes (conventionally colonized), but has no effect in the light period in zebrafish that are microbe-free. A number of BPA replacement chemicals were also assessed in colonized zebrafish. These data raise the possibility that BPA and replacement analogues may interact with microbiota to exert neurobehavioral effects. Ultimately, this study will provide valuable information to help improve risk assessment strategies, which do not currently consider interactions between microbiota and chemical toxicity.
Description:
Exposure to Bisphenol A (BPA), a high-production volume chemical and widespread environmental contaminant, has been associated with adverse endocrine and neurodevelopmental effects. Because host-associated microbial communities play important roles in normal nervous system development and harbor the ability to bioactivate or detoxify xenobiotics, we hypothesized that microbial colonization status may influence the neurobehavioral toxicity of BPA. To test this, conventionally colonized (CC), axenic (microbe-free), and axenic colonized with zebrafish facility water at 1 day post fertilization (dpf) zebrafish were exposed to BPA at 1, 6, 7, 8, and 9 dpf and assessed for morphological and neurobehavioral effects at 10 dpf. Exposure to BPA resulted in concentration-dependent hypoactivity in the dark period in all 3 cohorts. In contrast, significant hypoactivity was only observed in CC larvae in the light period. Growing public concern over the safety of BPA has resulted in swift replacement with a suite of alternatives that uniformly lack sufficient toxicity data. To compare toxicity profiles across replacement compounds, CC zebrafish were subsequently exposed to Bisphenol AF (BPAF), Bisphenol B (BPB), or Bisphenol S (BPS) using the same exposure paradigm and assessed for morphological and neurobehavioral effects at 10 dpf. The classic estrogen receptor agonist 17beta-estradiol (E2) was used as a positive control. A range of potencies was observed, based on the lowest observable effect concentration: BPAF > E2 > BPB > BPA > BPS. At 10 dpf, swimming behavior in larvae exposed to BPB, BPAF, or BPS was similar to DMSO control. In comparison, E2 exposure triggered concentration-dependent hypoactivity. Ongoing studies include analysis of DNA at 10 dpf to evaluate potential colonization status or chemical-dependent shifts in microbial community structure using 16S rRNA genomic-level sequencing. These data raise the possibility that BPA and replacement analogues may interact with microbiota to exert neurobehavioral effects. Ultimately, this study will provide valuable information to help improve risk assessment strategies, which do not currently consider interactions between microbiota and chemical toxicity. This abstract does not necessarily reflect EPA policy.