Effect of endocrine disrupting chemicals on the transcription of genes related to the innate immune system in the early developmental stage of zebrafish (Danio rerio)

Health concerns regarding the potential interference of endocrine disrupting chemicals (EDCs) in the immune system of wildlife and humans have increased in recent years. However, the effects of EDCs in aquatic systems on the immune system of fish species has only received limited attention. In the present study, we found that the mRNA levels of TNF alpha, IFN, IL-1 beta, IL-8, CXCL-Clc, and CC-chemokine, which are closely related to the innate immune system, were affected in newly hatched zebrafish when exposed to EDCs, such as 17 beta-estradiol, 17 alpha-ethynyestradiol, permethrin, atrazine and nonylphenol at various concentrations (0.1, 0.5, 2.5 and 12.5 mu g/l) for three days during the embryo stage. However, the different EDCs displayed different potentials to change innate immune-related gene transcription. Among the selected chemicals, permethrin (PM) and 17 beta-estradiol (E2) (12.5 mu g/l) significantly increased the mRNA levels of many cytokines, exhibiting their most prominent impacts on the innate immune system of zebrafish. In addition, it was found that the mixture of the above five chemicals (2.5 mu g/l each) had a greater effect on innate immune system-related gene transcription in zebrafish than equal amounts of the single compound. Moreover, the genes (such as Bcl2, Ucp2 and iNOS) relating to reactive oxygen species (ROS) and nitrogen reactive free radical production were also influenced by some EDCs and their mixture. We suggest that heavy oxidative stress and the balance of nitric oxide (NO) production lead to death of immune cells. These results may provide an explanation of the possible mode how EDCs influence the innate immune system in zebrafish. Taken together, the results obtained in the present study clearly demonstrate that EDCs and their mixtures in aquatic systems will greatly influence the immune system in fish, suggesting that the effects of EDCs on fish should be associated with immune toxicity. (C) 2010 Elsevier Ltd. All rights reserved.