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Transgenic zebrafish reveal tissue-specific differences in estrogen signaling in response to environmental water samples

Environmental Health Perspectives

By:
, , , , and
DOI: 10.1289/ehp.1307329

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Abstract

Background: Environmental endocrine disruptors (EED) 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 (ER) in the larval heart compared to 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 similar tissue-specific effects as 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 estrogen receptor genes by RNA in situ hybridization. Results: Selective patterns of ER activation were observed 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 is due to differences in the expression of estrogen receptor subtypes. ERα is expressed in developing heart valves but not in the liver, whereas ERβ2 has the opposite profile. Accordingly, subtype-specific ER agonists activate the reporter in either the heart valves or the liver. Conclusion: The use of 5xERE:GFP transgenic zebrafish has revealed an unexpected tissue-specific difference in the response to environmentally relevant estrogenic compounds. Exposure to estrogenic EEDs in utero is associated with adverse health effects, with the potentially unanticipated consequence of targeting developing heart valves.

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Additional Publication Details

Publication type:
Article
Publication Subtype:
Journal Article
Title:
Transgenic zebrafish reveal tissue-specific differences in estrogen signaling in response to environmental water samples
Series title:
Environmental Health Perspectives
DOI:
10.1289/ehp.1307329
Volume
122
Issue:
4
Year Published:
2014
Language:
English
Publisher:
National Institute of Environmental Health Sciences
Contributing office(s):
Leetown Science Center
Description:
26 p.
Larger Work Type:
Article
Larger Work Subtype:
Journal Article
Larger Work Title:
Environmental Health Perspectives
First page:
356
Last page:
362
Country:
United States
State:
New Jersey;Pennsylvania;Virginia;West Virginia
Online Only (Y/N):
Y