title: Transgenic zebrafish reveal tissue-specific differences in estrogen signaling in response to environmental water samples.
abstract: BACKGROUND
  Environmental endocrine disruptors (EEDs) are exogenous chemicals that mimic endogenous hormones such as estrogens. Previous studies using a zebrafish transgenic reporter demonstrated that the EEDs bisphenol A and genistein preferentially activate estrogen receptors (ERs) in the larval heart compared with the liver. However, it was not known whether the transgenic zebrafish reporter was sensitive enough to detect estrogens from environmental samples, whether environmental estrogens would exhibit tissue-specific effects similar to those of BPA and genistein, or why some compounds preferentially target receptors in the heart.
  
  
  METHODS
  We tested surface water samples using a transgenic zebrafish reporter with tandem estrogen response elements driving green fluorescent protein expression (5xERE:GFP). Reporter activation was colocalized with tissue-specific expression of ER genes by RNA in situ hybridization.
  
  
  RESULTS
  We observed selective patterns of ER activation in transgenic fish exposed to river water samples from the Mid-Atlantic United States, with several samples preferentially activating receptors in embryonic and larval heart valves. We discovered that tissue specificity in ER activation was due to differences in the expression of ER subtypes. ERα was expressed in developing heart valves but not in the liver, whereas ERβ2 had the opposite profile. Accordingly, subtype-specific ER agonists activated the reporter in either the heart valves or the liver.
  
  
  CONCLUSIONS
  The use of 5xERE:GFP transgenic zebrafish revealed an unexpected tissue-specific difference in the response to environmentally relevant estrogenic compounds. Exposure to estrogenic EEDs in utero was associated with adverse health effects, with the potentially unanticipated consequence of targeting developing heart valves.
authors.affiliation: Department of Embryology, Carnegie Institution for Science, Baltimore, Maryland, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Gorelick
authors.forename: Luke R
authors.initials: LR
authors.lastname: Iwanowicz
authors.forename: Alice L
authors.initials: AL
authors.lastname: Hung
authors.forename: Vicki S
authors.initials: VS
authors.lastname: Blazer
authors.forename: Marnie E
authors.initials: ME
authors.lastname: Halpern
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D052244:Endocrine Disruptors / Q000633:toxicity; D004967:Estrogens / Q000633:toxicity*; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D014599:Uterus / Q000187:drug effects / Q000378:metabolism; D015027:Zebrafish
chemical_list: D052244:Endocrine Disruptors; D004967:Estrogens; D011960:Receptors, Estrogen; D049452:Green Fluorescent Proteins