PUBLICATION
Estrogen-related receptor γ is an in vivo receptor of bisphenol A
- Authors
- Tohmé, M., Prud'homme, S.M., Boulahtouf, A., Samarut, E., Brunet, F., Bernard, L., Bourguet, W., Gibert, Y., Balaguer, P., Laudet, V.
- ID
- ZDB-PUB-140513-127
- Date
- 2014
- Source
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology 28(7): 3124-3133 (Journal)
- Registered Authors
- Brunet, Frederic G., Gibert, Yann, Laudet, Vincent
- Keywords
- endocrine disrupters, otolith, zebrafish
- MeSH Terms
-
- Animals
- Benzhydryl Compounds/pharmacology*
- Otolithic Membrane/drug effects
- Otolithic Membrane/metabolism
- Phenols/pharmacology*
- Protein Binding/drug effects*
- Receptors, Estrogen/metabolism*
- Zebrafish/metabolism*
- PubMed
- 24744145 Full text @ FASEB J.
- CTD
- 24744145
Citation
Tohmé, M., Prud'homme, S.M., Boulahtouf, A., Samarut, E., Brunet, F., Bernard, L., Bourguet, W., Gibert, Y., Balaguer, P., Laudet, V. (2014) Estrogen-related receptor γ is an in vivo receptor of bisphenol A. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 28(7):3124-3133.
Abstract
Bisphenol A (BPA) is an endocrine disruptor that displays estrogenic activity. Several reports suggest that BPA may have estrogen receptor-independent effects. In zebrafish, 50 μM BPA exposure induces otic vesicle abnormalities, including otolith aggregation. The purpose of this study was to test if BPA action was mediated in vivo during zebrafish development by the orphan nuclear estrogen related receptor (ERR) γ. Combining pharmacological and functional approaches, we demonstrate that the zebrafish ERRγ mediates BPA-induced malformations in otoliths. Using different bisphenol derivatives, we show that different compounds can induce a similar otolith phenotype than BPA and that the binding affinity of these derivatives to the zebrafish ERRγ correlates with their ability to induce otolith malformations. Morpholino knockdown of ERRγ function suppresses the BPA effect on otoliths whereas overexpression of ERRγ led to a BPA-like otolith phenotype. Moreover, a subphenotypical dose of BPA (1 μM) combined with ERRγ overexpression led to a full-dose (50 μM) BPA otolith phenotype. We therefore conclude that ERRγ mediates the otic vesicle phenotype generated by BPA. Our results suggest that the range of pathways perturbed by this compound and its potential harmful effect are larger than expected.-Tohmé, M., Prud'homme, S. M., Boulahtouf, A., Samarut, E., Brunet, F., Bernard, L., Bourguet, W., Gibert, Y., Balaguer, P., Laudet, V. Estrogen-related receptor γ is an in vivo receptor of bisphenol A.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping