Sustained Effects of Developmental Exposure to Inorganic Arsenic on Hepatic Gene Expression and Mating Success in Zebrafish

Abstract

ABSTRACTThe impacts of exposure to the pervasive environmental toxicant, inorganic arsenic (iAs), on human and fish health are well characterized and several lines of evidence suggest that some impacts can manifest years after exposure cessation. Using a developmental exposure protocol whereby zebrafish embryos were exposed to 0.5 and 1.5 mM iAs from 4-120 hours post fertilization (hpf) and then was removed, we investigated the sustained effects of iAs on gene expression in the liver, survival, reproductive success, and susceptibility to iAs toxicity in the subsequent generation. Developmental exposure to iAs has massive effects on the hepatic transcriptome, with 23% of genes differentially expressed at the end of exposure at 120 hpf, and some of these genes remain deregulated in the liver 9 months after iAs was removed. Developmental exposure to 1.5 mM iAs, but not 0.5 mM, increased mortality through 3 months by over 50%. Adults that were developmentally exposed to 0.5 mM iAs had reduced mating success, but their offspring had no differences in observable aspects of development or their susceptibility to iAs toxicity. This demonstrates that developmental exposure of zebrafish to iAs reduces long-term survival, reproductive success and causes sustained changes to gene expression in the liver.SUMMARY STATEMENTThis work investigates the long-term effects of developmental exposure to inorganic arsenic (iAs) using zebrafish. Months after iAs-exposure was terminated, we found increased mortality, changes in gene expression in the liver and decreased mating success.