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The phytoestrogen genistein affects zebrafish development through two different pathways

Sassi-Messai, Sana, Gibert, Yann, Bernard, Laure, Nishio, Shin-Ichi, Ferri, Lagneau Karine F., Molina, Jose, Andersson-Lendhal, Monika, Benoit, Gerard, Balaguer, Patrick and Laudet, Vincent 2009, The phytoestrogen genistein affects zebrafish development through two different pathways, PLoS one, vol. 4, no. 3, pp. 1-13, doi: 10.1371/journal.pone.0004935.

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Title The phytoestrogen genistein affects zebrafish development through two different pathways
Author(s) Sassi-Messai, Sana
Gibert, Yann
Bernard, Laure
Nishio, Shin-Ichi
Ferri, Lagneau Karine F.
Molina, Jose
Andersson-Lendhal, Monika
Benoit, Gerard
Balaguer, Patrick
Laudet, Vincent
Journal name PLoS one
Volume number 4
Issue number 3
Article ID e4935
Start page 1
End page 13
Total pages 13
Publisher Public Library of Science
Place of publication San Francisco, California
Publication date 2009-03-25
ISSN 1932-6203
Keyword(s) estrogen pathway
genistein
zebrafish embryos
Summary Background
Endocrine disrupting chemicals are widely distributed in the environment and derive from many different human activities or can also be natural products synthesized by plants or microorganisms. The phytoestrogen, genistein (4′, 5, 7-trihydroxy-isoflavone), is a naturally occurring compound found in soy products. Genistein has been the subject of numerous studies because of its known estrogenic activity.

Methodology/ Principal Findings
We report that genistein exposure of zebrafish embryos induces apoptosis, mainly in the hindbrain and the anterior spinal cord. Timing experiments demonstrate that apoptosis is induced during a precise developmental window. Since adding ICI 182,780, an ER antagonist, does not rescue the genistein-induced apoptosis and since there is no synergistic effect between genistein and estradiol, we conclude that this apoptotic effect elicited by genistein is estrogen-receptors independent. However, we show in vitro, that genistein binds and activates the three zebrafish estrogen receptors ERα, ERβ-A and ERβ-B. Furthermore using transgenic ERE-Luciferase fish we show that genistein is able to activate the estrogen pathway in vivo during larval stages. Finally we show that genistein is able to induce ectopic expression of the aromatase-B gene in an ER-dependent manner in the anterior brain in pattern highly similar to the one resulting from estrogen treatment at low concentration.

Conclusion/Significance
Taken together these results indicate that genistein acts through at least two different pathways in zebrafish embryos: (i) it induces apoptosis in an ER-independent manner and (ii) it regulates aromatase-B expression in the brain in an ER-dependent manner. Our results thus highlight the multiplicity of possible actions of phytoestrogens, such as genistein. This suggests that the use of standardized endpoints to study the effect of a given compound, even when this compound has well known targets, may carry the risk of overlooking interesting effects of this compound.
Language eng
DOI 10.1371/journal.pone.0004935
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2009, The Authors
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30062870

Document type: Journal Article
Collections: School of Medicine
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.