title: Histopathologic alterations associated with global gene expression due to chronic dietary TCDD exposure in juvenile zebrafish.
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.
authors.affiliation: Department of Biological Sciences, University of Wisconsin-Milwaukee, Lapham Hall, Milwaukee, Wisconsin, United States of America; School of Freshwater Sciences, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, United States of America.
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Microbiology, Oregon State University, Nash Hall, Corvallis, Oregon, United States of America.
authors.forename: Jan M
authors.initials: JM
authors.lastname: Spitsbergen
authors.affiliation: LUNAM Université, Oniris, Laboratoire d'Etude des Résidus et Contaminants dans les Aliments (LABERCA), Nantes, France.
authors.forename: Ronan
authors.initials: R
authors.lastname: Cariou
authors.affiliation: Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, United States of America.
authors.forename: Chun-Yuan
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Roche NimbleGen, Inc., Madison, Wisconsin, United States of America.
authors.forename: Nan
authors.initials: N
authors.lastname: Jiang
authors.affiliation: School of Aquatic and Fishery Sciences, University of Washington, Seattle Washington, United States of America.
authors.forename: Giles
authors.initials: G
authors.lastname: Goetz
authors.affiliation: Department of Biological Sciences, University of Wisconsin-Milwaukee, Lapham Hall, Milwaukee, Wisconsin, United States of America.
authors.forename: Reinhold J
authors.initials: RJ
authors.lastname: Hutz
authors.affiliation: Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, United States of America; Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America; Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Tonellato
authors.affiliation: Department of Biological Sciences, University of Wisconsin-Milwaukee, Lapham Hall, Milwaukee, Wisconsin, United States of America; School of Freshwater Sciences, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, United States of America.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Carvan
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004785:Environmental Pollutants / Q000009:adverse effects* / Q000494:pharmacology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D023281:Genomics; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000009:adverse effects* / Q000494:pharmacology; D015027:Zebrafish / Q000196:embryology*
chemical_list: D015415:Biomarkers; D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins