| Autor: |
Meyer DN; Department of Environmental and Global Health, University of Florida, Gainesville, FL, USA.; Department of Pharmacology, Wayne State University, Detroit, MI, USA.; Institute of Environmental Health Sciences, Wayne State University, Detroit, MI, USA., Silva I; Department of Environmental and Global Health, University of Florida, Gainesville, FL, USA., Vo B; Department of Environmental and Global Health, University of Florida, Gainesville, FL, USA., Paquette A; Department of Environmental and Global Health, University of Florida, Gainesville, FL, USA., Blount JR; Institute of Environmental Health Sciences, Wayne State University, Detroit, MI, USA., George SE; School of Veterinary Medicine, University of Madison-Wisconsin, Madison, WI, USA., Gonzalez G; Department of Environmental and Global Health, University of Florida, Gainesville, FL, USA., Cavaneau E; Department of Environmental and Global Health, University of Florida, Gainesville, FL, USA., Khalaf A; Institute of Environmental Health Sciences, Wayne State University, Detroit, MI, USA., Petriv AM; Institute of Environmental Health Sciences, Wayne State University, Detroit, MI, USA., Wu CC; Department of Environmental and Global Health, University of Florida, Gainesville, FL, USA.; Institute of Environmental Health Sciences, Wayne State University, Detroit, MI, USA., Haimbaugh A; Department of Pharmacology, Wayne State University, Detroit, MI, USA.; Institute of Environmental Health Sciences, Wayne State University, Detroit, MI, USA., Baker TR; Department of Environmental and Global Health, University of Florida, Gainesville, FL, USA.; Department of Pharmacology, Wayne State University, Detroit, MI, USA.; Institute of Environmental Health Sciences, Wayne State University, Detroit, MI, USA. |
| Abstrakt: |
Exposure to 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD), an environmental endocrine disruptor and model AhR agonist, is linked to skeletal abnormalities, cardiac edema, stunted growth rate, altered metabolism, and neurobehavioral deficits. We have previously reported transgenerational reproductive outcomes of developmental TCDD exposure in adult zebrafish ( Danio rerio ), an NIH-validated model for developmental and generational toxicology. Using the same paradigm of sublethal TCDD exposure (50 pg/ml) at both 3 and 7 weeks post fertilization (wpf), we investigated several novel endpoints, including longitudinal morphometrics and anxiety-linked behavior, in fish exposed as juveniles. We also assessed developmental abnormalities and neurobehavior in their F 1 larval offspring. TCDD exposure induced timepoint-dependent decreases in several craniofacial and trunk morphometrics across juvenile development. In early adulthood, however, only exposed males underwent a transient period of compensatory growth, ending between 7 and 12 months post fertilization (mpf). At 12 mpf, exposed adult fish of both sexes displayed increased exploratory behaviors in a novel tank test. The F 1 offspring of parents exposed at both 3 and 7 wpf were hyperactive, but neurobehavioral outcomes diverged depending on parental exposure window. F 1 exposure-lineage larvae had increased rates of edema and skeletal abnormalities, but fewer unhatched larvae compared to controls. Parent- and timepoint-specific effects of exposure on abnormality rate were also evaluated; these outcomes were considerably less severe. Our novel behavioral findings expand current knowledge of the long-term and intergenerational consequences of early-life TCDD exposure in a zebrafish model, in addition to delineating minor longitudinal morphometric changes in exposed fish and abnormalities in larval offspring. |
