The impact of endocrine‐disrupting chemicals on oxidative stress and innate immune response in zebrafish embryos

Abstract

Bisphenol A (BPA) and nonylphenol (NP) are well known endocrine-disrupting chemicals (EDCs) ubiquitous in the aquatic environment and are an ecotoxicological risk for the health of aquatic organisms. Limited attention has been given to the immunotoxicity of these chemicals. The present study revealed a concentration-dependent increase of reactive oxygen species content and an induced expression of redox-sensitive transcription factors in zebrafish embryos after exposure to various concentrations of BPA, NP, and BPA/NP mixture for 4 h to 168 h postfertilization. Transcription of genes related to the immune response, including IFNγ, IL1β, IL10, Mx, TNFα, CC-chemokine, and CXCL-clc, were significantly up-regulated on exposure to EDCs. A significant induction of concentrations of proinflammatory mediator, nitric oxide, accompanied by an increase in the activity of nitric oxide synthase (NOS) and an upregulation of inducible NOS gene expression, was detected in zebrafish embryos on exposures to EDCs. To elucidate the potential mechanisms by which BPA and NP activate the innate immune response, expression profiles of genes related to the Toll-like receptors (TLRs) signaling pathway were examined. Expressions of TLR3, TRIF, MyD88, SARM, IRAK4, and TRAF6 were altered on exposure to EDCs. The authors' results demonstrate that exposure to BPA and NP significantly affects the expression of genes related to immune response in zebrafish embryos following oxidative stress.

Estrogen receptor 2b deficiency impairs the antiviral response of zebrafish

“…These observations reflect those of previous studies depicting the activation of classical nuclear Esrs as capable of strongly affecting fish leukocyte gene expression, not only through transcriptomal alteration, but also through the modulation of the proteome metabolism (Liarte et al, 2011c). While some works developed using human cells point to the ability of estrogenic compounds to enhance IFNs and TLRs expression despite the lack of estrogen responsive elements in their promoters (Lindner et al, 1997;Seillet et al, 2012), our data contrast with the little evidence existing about immune impairment after estrogenic EDC exposure in the zebrafish (Xu et al, 2013). Whatever the outcome, the drastic induction of socs1 in Esr2b mutant zebrafish would establish a faulty antiviral response in the early stages of the infection, enabling the virus to quickly replicate and disseminate, as demonstrated by the expression levels of its viral capsid protein.…”

The In Vitro Immune Modulatory Effect of Bisphenol A on Fish Macrophages via Estrogen Receptor α and Nuclear Factor-κB Signaling

“…With increased BPA exposure, ROS and NO levels, iNOS and TNOS activities, as well as immune gene expression such as IL-1β, IL-10 in the macrophages was significantly induced in a concentration-dependent manner, consistent with our previous in vivo observations on zebrafish embryos upon 7 day BPA treatment. 21 Moreover, the alterations of most tested parameters were significantly correlated (SI Table S2), indicating a coordinated modulation process in macrophages responded to increased BPA exposure. Consistent with our observation on M17 (IL-6 like), Liu et al 25 have showed that BPA treatment increased pro-inflammatory cytokines IL-6 and tumor necrosis factor-α (TNF-α) production in THP1 macrophages and primary human macrophages at BPA concentrations of 0.01 and 0.1 μM, that is, about 2 and 20 μg/L.…”

Estimation of blood free radical levels in healthy population pre and post yoga

“…Exposure to several manmade chemicals, organic pollutants, endocrine disrupting chemicals like insecticides, pesticides, bisphenol A, phthalates not only disrupt the hypothalmopitutary gonadal axis but also induce oxidative stress. 31 A sedentary life style, fast foods, smoking, excess alcohol intake, electromagnetic radiation, high temperature all result in exposure to increased free radical levels. Thus free radicals can be produced by both exogenous and endogenous sources.…”