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Cadmium: An Endocrine Disrupter That Affects Gene Expression in the Liver and Brain of Juvenile Rainbow Trout¹

Endocrinologie Moléculaire de la Reproduction, UMR-CNRS 6026, Université de Rennes 1, Campus de Beaulieu, 35042 Rennes cedex, France

An inhibition of vitellogenesis is observed in fish exposed to cadmium (Cd), either in natural or in experimental conditions. To investigate whether this correlates or not with modifications in the expression of several genes involved in reproduction, we have performed a study on juvenile rainbow trout (Oncorhynchus mykiss) exposed to waterborne Cd in combination with estradiol (E₂). A relative reverse transcription-PCR protocol was used to evaluate the effect of Cd exposure on the expression of several genes. We quantified vitellogenin, rainbow trout estradiol receptor (rtER), short and long isoforms (rtERS and rtERL), mRNA levels in liver, and salmon GnRH1, salmon GnRH2, rtERS, and rtERL mRNA levels in the brain. In liver, Cd reduced the E₂-stimulated mRNA levels of vitellogenin as well as these of both rtER isoforms in a dose-dependent manner. In brain tissue, our results indicate that rtER mRNA levels are not enhanced by E₂. Cd treatments did not modify rtERS isoform expression but reduced rtERL expression in the brain. Focusing on the expression of salmon GnRH (sGnRH) genes, E₂ did not affect mRNA levels, but experiments with Cd alone greatly enhanced sGnRH 1 as well as sGnRH 2 gene expression in a dose-dependant manner. This study supports the idea that Cd is an important endocrine disrupter that could act through an inhibition of E₂-stimulated genes in the liver and also through a central effect on sGnRH gene expression. Cd may affect a number of E₂ signaling pathways but could also affect the reproductive axis by nonestrogenic mechanisms.

¹ This work was supported by CNRS, INRA, and EU (BIO4 CT 97-0554). A.V. was supported by a grant from Conseil Regional de Bretagne (France). Preliminary results were presented at the 20th Conference of European Comparative Endocrinologists (Faro, Portugal).

² Correspondence: Angelique Vetillard, MRC Toxicology Unit, University of Leicester, Lancaster Road, Leicester, LE1 9HN, UK. FAX: +44 116 252 5616; av33{at}le.ac.uk

³ Current address: Department of Biology, University of Leicester, University road, Leicester LE1 7RH, UK

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