Toxicology

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

Abstract
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 the reproduction, we have performed a study on juvenile rainbow trout (Oncorhynchus mykiss) exposed to waterborne Cd in combination with estradiol (E2). A relative RT-PCR protocol was used to evaluate the effect of Cd exposure on the expression of several genes. We quantified vitellogenin, rainbow trout estradiol receptors (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 non-estrogenic mechanisms.

Key words: Neuroendocrinology • Toxicology • Estradiol receptor • Gene regulation • Gonadotropin-releasing hormone

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