Effect of BPA on cytokine expression and regeneration in larval zebrafish

Abstract Bisphenol-A (BPA) binds to estrogen receptors ER-α and β and is used in the production of polycarbonate plastic and epoxy resins. BPA presents a potential environmental challenge to the immune system of both humans and wildlife due to its use in food containers and thermal receipts and its resulting presence in surface water and wastewater runoff. We observed that BPA exposure downregulates the expression of the chemokine that functions to recruit neutrophils in both mice (KC) and zebrafish (cxcl8) and that it decreases neutrophil recruitment to the injury site in MPO::GFP zebrafish. Neutrophils are essential for the removal of damaged tissue and invading microbes, thus facilitating tissue regeneration of the tail fin. To investigate BPA’s effects on larval zebrafish tail regeneration, we induced a tail injury at day 3 post fertilization (dpf) and measured tail fin growth at day 1 and 3 post injury (dpi). Fish exposed to 100 ng/ml BPA regenerate a smaller tail fin area at 3 dpi (p-value < 0.01). We hypothesized that BPA exposure and altered neutrophil recruitment could affect regeneration by directly altering the expression of regeneration-related genes wnt10a and il-10 or their downstream genes and/or indirectly by regulating inflammatory genes including il-1 and il-6. The expression of il-1, il-6, il-10, and wnt10a were detected in zebrafish embryos from 2–6 dpf using qPCR. BPA exposure reduces both il-1 and il-6 expression 3 hours post-injury, suggesting that BPA reduces the inflammatory response. To determine whether BPA alters gene expression of wnt10a, il-10, or their downstream-regulated genes qPCR will be performed at 24- and 72-hours post-injury. Supported by Carleton College.