Citation:

Catron, T., D. Phelps, S. Keely, N. Brinkman, E. Anneken, A. Kvasnicka, C. Wood, AND S. Gaballah. Alterations in microbiota structure and neurobehavior in zebrafish following developmental exposure to estrogenic compounds. Society of Environmental Toxicology and Chemistry (SETAC) North America 38th Annual Meeting, Minneapolis, Minnesota, November 12 - 16, 2017.

Impact/Purpose:

Intestinal microbes are thought to play important roles in development of the nervous system. It has been proposed that microbiota, through bioactivation or detoxification, may mediate the developmental neurotoxicity of environmental chemicals. This work shows that exposure to 17beta-estradiol, a potent estrogen receptor agonist, causes neurotoxicity only in zebrafish with microbes. However, no alterations in microbial community structure were observed, suggesting that E2-induced developmental neurotoxicity may be mediated by microbiota. Exposure to bisphenol A and replacement compounds did not alter neurobehavior in zebrafish with or without microbes. However, concentration-dependent disruption of microbiota was observed with some of these compounds. 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. Growing public concern over the safety of BPA has resulted in swift replacement with a suite of alternatives that uniformly lack sufficient toxicity data. 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 developmental exposure to BPA or alternatives may influence microbiota structure and/or neurotoxicity. To test this, a semi-static system was used to expose conventionally colonized zebrafish to BPA, Bisphenol AF (BPAF), Bisphenol B (BPB), Bisphenol F (BPF), or Bisphenol S (BPS). The classic estrogen receptor agonist 17beta-estradiol (E2) was used as a positive control. At 10 days post fertilization (dpf), larvae were assessed for mortality and neurobehavioral effects using an established light/dark behavioral assay, and 16S rRNA gene sequencing was used to identify chemical-dependent changes in microbial community structure. Based on initial survival assessments, a range of potencies was observed: BPAF > E2 > BPB > BPA > BPF > BPS. At 10 dpf, swimming behavior in conventionally colonized larvae exposed to BPA, BPAF, BPB, BPF or BPS was similar to DMSO control. In comparison, E2 exposure triggered concentration-dependent hypoactivity. To assess whether microbial colonization status may influence the neurobehavioral toxicity of E2, conventionally colonized, axenic (microbe-free), and axenic colonized with zebrafish facility water at 1 dpf larvae were exposed to 0.4 or 1.2 µM E2. Hypoactivity was only observed in colonized larvae. In addition, exposure to E2, BPB, and BPAF did not alter microbiota structure, while concentration-dependent disruption of microbiota was observed following exposure to BPA, BPF, and BPS. Combined, these data suggest that E2-induced neurotoxicity may be mediated by microbiota. Although exposure to bisphenol compounds did not alter neurobehavior in 10 dpf conventionally colonized larvae, it is currently unclear whether disruption of microbiota during development adversely affects the host. This abstract does not necessarily reflect EPA policy.

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