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ToxSci Advance Access originally published online on July 24, 2008
Toxicological Sciences 2008 106(1):113-123; doi:10.1093/toxsci/kfn151
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© The Author 2008. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Altered Sexual Development in Roach (Rutilus rutilus) Exposed to Environmental Concentrations of the Pharmaceutical 17{alpha}-Ethinylestradiol and Associated Expression Dynamics of Aromatases and Estrogen Receptors

Anke Lange*,1, Yoshinao Katsu{dagger}, Rie Ichikawa{dagger}, Gregory C. Paull*, Laura L. Chidgey*, Tobias S. Coe*, Taisen Iguchi{dagger} and Charles R. Tyler*

* School of Biosciences, University of Exeter, Exeter, Devon EX4 4PS, UK {dagger} Okazaki Institute for Integrative Bioscience, National Institute for Basic Biology, National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji, Okazaki 444-8787, Japan

1 To whom correspondence should be addressed at School of Biosciences, University of Exeter, Prince of Wales Road, Exeter, Devon EX4 4PS, UK. Fax: +44-1392-263700. E-mail: a.lange{at}exeter.ac.uk.

Received May 2, 2008; accepted July 19, 2008


  Abstract

Wild roach (Rutilus rutilus) inhabiting UK rivers contaminated with estrogenic effluents from wastewater treatment works show altered sexual development, including intersex, and this can impact negatively on their reproductive capabilities. The molecular events underlying these disruptions in gender assignment, however, are still poorly understood. In this study, two isoforms of aromatase (cyp19a1a and cyp19a1b) were cloned from the roach, and effects of exposure to 17{alpha}-ethinylestradiol (EE2) during early life were determined on the expression of both aromatases and on the estrogen receptors (ERs) (subtypes esr1 and esr2b) and analyzed against effects on the progression of gonadal sex differentiation. Exposure to environmentally relevant concentrations of EE2 during the critical period of sex differentiation resulted in gonadal feminization and all roach exposed to 4 ng EE2/l were females. These effects on gonadal development were associated with alterations in the expression of both esr and cyp19a1 genes in bodies and heads of exposed fish with the most marked effects on the expression of esr1 and cyp19a1b. Our findings show that both aromatase isoforms and both ER subtypes are associated with sexual differentiation in roach, and alterations in their expression can signal for disruptions in sexual development.

Key Words: aromatases; developmental gene expression dynamics; endocrine disruption; estrogen receptors; 17{alpha}-ethinylestradiol; feminization.


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