title: Biosensor zebrafish provide new insights into potential health effects of environmental estrogens.
abstract: BACKGROUND
  Environmental estrogens alter hormone signaling in the body that can induce reproductive abnormalities in both humans and wildlife. Available testing systems for estrogens are focused on specific systems such as reproduction. Crucially, however, the potential for significant health impacts of environmental estrogen exposures on a variety of body systems may have been overlooked.
  
  
  OBJECTIVE
  Our aim was to develop and apply a sensitive transgenic zebrafish model to assess real-time effects of environmental estrogens on signaling mechanisms in a whole body system for use in integrated health assessments.
  
  
  METHODS
  We created a novel transgenic biosensor zebrafish containing an estrogen-inducible promoter derived with multiple tandem estrogen responsive elements (EREs) and a Gal4ff-UAS system for enhanced response sensitivity.
  
  
  RESULTS
  Using our novel estrogen-responsive transgenic (TG) zebrafish, we identified target tissues for environmental estrogens; these tissues have very high sensitivity even at environmentally relevant concentrations. Exposure of the TG fish to estrogenic endocrine-disrupting chemicals (EDCs) induced specific expression of green fluorescent protein (GFP) in a wide variety of tissues including the liver, heart, skeletal muscle, otic vesicle, forebrain, lateral line, and ganglions, most of which have not been established previously as targets for estrogens in fish. Furthermore, we found that different EDCs induced GFP expression with different tissue response patterns and time trajectories, suggesting different potential health effects.
  
  
  CONCLUSIONS
  We have developed a powerful new model for understanding toxicological effects, mechanisms, and health impacts of environmental estrogens in vertebrates.
authors.affiliation: Biosciences, College of Life and Environmental Sciences, University of Exeter, Exeter, United Kingdom.
authors.forename: Okhyun
authors.initials: O
authors.lastname: Lee
authors.forename: Aya
authors.initials: A
authors.lastname: Takesono
authors.forename: Masazumi
authors.initials: M
authors.lastname: Tada
authors.forename: Charles R
authors.initials: CR
authors.lastname: Tyler
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Kudoh
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics / Q000378:metabolism*; D015374:Biosensing Techniques / Q000379:methods*; D004967:Estrogens / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism*
chemical_list: D004967:Estrogens; D049452:Green Fluorescent Proteins