Developmental toxicity, EROD, and CYP1A mRNA expression in zebrafish embryos exposed to dioxin‐like PCB126

Abstract

Dioxin-like PCB126 is a persistent organic pollutant that causes a range of syndromes including developmental toxicity. Dioxins have a high affinity for aryl hydrocarbon receptor (AhR) and induce cytochrome P4501A (CYP1A). However, the role of CYP1A activity in developmental toxicity is less clear. To better understand dioxin induced developmental toxicity, we exposed zebrafish (Danio rerio) embryos to PCB126 at concentrations of 0, 16, 32, 64, and 128 μg L(-1) from 3-h post-fertilization (hpf) to 168 hpf. The embryonic survival rate decreased at 144 and 168 hpf. The fry at 96 hpf displayed gross developmental malformations, including pericardial and yolk sac edema, spinal curvature, abnormal lower jaw growth, and non-inflated swim bladder. The pericardial and yolk sac edema rate significantly increased and the heart rate declined from 96 hpf compared with the controls. PCB126 did not alter the hatching rate. To elucidate the mechanism of PCB126-induced developmental toxicity, we conducted ethoxyresorufin-O-deethylase (EROD) in vivo assay to determine CYP1A enzyme activity, and real-time PCR to study the induction of CYP1A mRNA gene expression in embryo/larval zebrafish at 24, 72, 96, and 132 hpf. In vivo EROD activity was induced by PCB126 at 16 μg L(-1) concentration as early as 72 hpf but significant increases were observed only in zebrafish exposed to 64 and 128 μg L(-1) doses (p < 0.005) at 72, 96, and 132 hpf. Induction of CYP1A mRNA expression was significantly upregulated in zebrafish exposed to 32 and 64 μg L(-1) at 24, 72, 96, and 132 hpf. Overall, the severe pericardial and yolk sac edema and reduced heart rate suggest that heart defects are a sensitive endpoint, and the general trend of dose-dependent increase in EROD activity and induction of CYP1A mRNA gene expression provide evidence that the developmental toxicity of PCB126 to zebrafish embryos is mediated by activation of AhR.

Imidacloprid exposure cause the histopathological changes, activation of TNF-α, iNOS, 8-OHdG biomarkers, and alteration of caspase 3, iNOS, CYP1A, MT1 gene expression levels in common carp (Cyprinus carpio L.)

“…Mesnage et al (2014) showed that imidacloprid increases the caspase 3 mRNA expression level in human cell lines (HepG2, HEK293, and JEG3) [ 56 ]. Furthermore, imidacloprid exposure results in apoptosis in chicken embryos [ 57 ]. There are currently no reports concerning caspase 3 activation after IMI treatment in the brain of the common carp.…”

Zebrafish as a Model for Toxicological Perturbation of Yolk and Nutrition in the Early Embryo

“…Compounds including TCDD classically induce “blue sac syndrome,” a pathology characterized by yolk sac and pericardial edema [61]. However, a wide array of toxicants including polycyclic aromatic hydrocarbons [63, 64], polychlorinated biphenyls [65, 66], polybrominated flame retardants [67], poly- and perfluorinated compounds [68, 69] (unpublished data), organophosphates [70–73], herbicides [74–76], and nanoparticles [67, 77–79] among others have been demonstrated to cause yolk sac edema in zebrafish embryos. The wide range of chemical properties demonstrated by these chemicals suggests that yolk sac edema is an especially sensitive toxicological outcome for embryonic evaluation.…”

Adsorption of B(α)P on carbon nanopowder affects accumulation and toxicity in zebrafish (Danio rerio) embryos

“…54 The expression pattern of cyp1a has been extensively investigated in zebrafish embryos, either under physiological condition or exposed to environmental pollutants. 55,56 Significant transcription of cyp1a mRNA has been observed in zebrafish embryos already at 24 hpf localizing in almost all tissues. The inducibility of cyp1a transcription by dioxinlike pollutants has been also established.…”