Vetillard Angelique, Bailhache Thierry
Endocrinologie Moléculaire de la Reproduction, UMR-CNRS 6026, Université de Rennes 1, Campus de Beaulieu, 35042 Rennes cedex, France.
Biol Reprod. 2005 Jan;72(1):119-26. doi: 10.1095/biolreprod.104.029520. Epub 2004 Aug 18.
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 alpha (rtERalpha), short and long isoforms (rtERalphaS and rtERalphaL), mRNA levels in liver, and salmon GnRH1, salmon GnRH2, rtERalphaS, and rtERalphaL mRNA levels in the brain. In liver, Cd reduced the E2-stimulated mRNA levels of vitellogenin as well as these of both rtERalpha isoforms in a dose-dependent manner. In brain tissue, our results indicate that rtERalpha mRNA levels are not enhanced by E2. Cd treatments did not modify rtERalphaS isoform expression but reduced rtERalphaL 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.
在自然或实验条件下接触镉（Cd）的鱼类中，观察到了卵黄生成的抑制现象。为了研究这是否与参与生殖的几个基因表达的改变相关，我们对暴露于水溶态镉与雌二醇（E2）组合环境中的虹鳟幼鱼（Oncorhynchus mykiss）进行了一项研究。采用相对逆转录 - PCR方案来评估镉暴露对几个基因表达的影响。我们对肝脏中的卵黄蛋白原、虹鳟雌二醇受体α（rtERalpha）、短和长亚型（rtERalphaS和rtERalphaL）的mRNA水平，以及大脑中的鲑鱼GnRH1、鲑鱼GnRH2、rtERalphaS和rtERalphaL的mRNA水平进行了定量。在肝脏中，镉以剂量依赖的方式降低了E2刺激的卵黄蛋白原mRNA水平以及两种rtERalpha亚型的mRNA水平。在脑组织中，我们的结果表明E2不会提高rtERalpha mRNA水平。镉处理并未改变rtERalphaS亚型的表达，但降低了大脑中rtERalphaL的表达。关注鲑鱼GnRH（sGnRH）基因的表达，E2不影响mRNA水平，但单独使用镉的实验以剂量依赖的方式极大地增强了sGnRH 1以及sGnRH 2基因的表达。这项研究支持了这样一种观点，即镉是一种重要的内分泌干扰物，它可能通过抑制肝脏中E2刺激的基因起作用，也可能通过对sGnRH基因表达的中枢效应起作用。镉可能影响许多E2信号通路，但也可能通过非雌激素机制影响生殖轴。
