Histopathologic Alterations Associated with Global Gene Expression Due to Chronic Dietary TCDD Exposure in Juvenile Zebrafish

Chun-Yuan Huang,Qing Liu,Nan Jiang,Peter J. Tonellato,Ronan Cariou,Michael J. Carvan,Giles Goetz,Jan M. Spitsbergen,Reinhold J. Hutz,Robert L. Tanguay

doi:10.1371/journal.pone.0100910

Abstract

The goal of this project was to investigate the effects and possible developmental disease implication of chronic dietary TCDD exposure on global gene expression anchored to histopathologic analysis in juvenile zebrafish by functional genomic, histopathologic and analytic chemistry methods. Specifically, juvenile zebrafish were fed Biodiet starter with TCDD added at 0, 0.1, 1, 10 and 100 ppb, and fish were sampled following 0, 7, 14, 28 and 42 d after initiation of the exposure. TCDD accumulated in a dose- and time-dependent manner and 100 ppb TCDD caused TCDD accumulation in female (15.49 ppb) and male (18.04 ppb) fish at 28 d post exposure. Dietary TCDD caused multiple lesions in liver, kidney, intestine and ovary of zebrafish and functional dysregulation such as depletion of glycogen in liver, retrobulbar edema, degeneration of nasal neurosensory epithelium, underdevelopment of intestine, and diminution in the fraction of ovarian follicles containing vitellogenic oocytes. Importantly, lesions in nasal epithelium and evidence of endocrine disruption based on alternatively spliced vasa transcripts are two novel and significant results of this study. Microarray gene expression analysis comparing vehicle control to dietary TCDD revealed dysregulated genes involved in pathways associated with cardiac necrosis/cell death, cardiac fibrosis, renal necrosis/cell death and liver necrosis/cell death. These baseline toxicological effects provide evidence for the potential mechanisms of developmental dysfunctions induced by TCDD and vasa as a biomarker for ovarian developmental disruption.

Highlights

TCDD is a highly toxic, widespread environmental chemical that is a by-product of incinerating plastics, chlorinated industrial chemicals and other hydrocarbons
Significant decreases of body length were observed in male zebrafish in the 10 and 100 ppb TCDD-treatment groups at 28 d
In the 1 ppb group, there was a technical failure during analysis and the samples were destroyed, we lack TCDD assimilation data of in the 1-ppb group at 14 d

Summary

Introduction

TCDD is a highly toxic, widespread environmental chemical that is a by-product of incinerating plastics, chlorinated industrial chemicals and other hydrocarbons. TCDD has been shown to persist in the environment, bioaccumulate in humans and wildlife through trophic transfer [1] and contributes to adverse diseasespecific effects such as cancer and cardiovascular toxicity [2,3,4,5]. As an aquatic animal model, continues to play a central role in TCDD toxicological developmental and genetic research [6]. TCDD has been found to cause precursor and diseaseassociated adverse effects in zebrafish embryos, such as craniofacial malformations in jaw, edema in yolk sac and pericardium, decreases in cardiac output [7], spinal deformity [8], disruption of development of common cardinal vein [9], and a developmental reduction in blood flow in mesencephalic vein [10]. TCDD represses the follicle maturation in ovarian development and inhibits estradiol biosynthesis [12]

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