Identification of candidate genes and physiological pathways involved in gonad deformation in whitefish (Coregonus spp.) from Lake Thun, Switzerland.

Identification of candidate genes and physiological pathways involved in gonad deformation in whitefish (Coregonus spp.) from Lake Thun, Switzerland.
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DOI:
10.3390/ijerph8072706
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发表时间:
2011-07
影响因子:
--
通讯作者:
Largiadèr CR
Largiadèr CR
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Bittner D;Cossins AR;Segner H;Excoffier L;Largiadèr CR

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2000年,渔民报告了瑞士图恩湖白鱼(Coregonus spp.)生殖器官畸形的现象。尽管进行了深入的调查,但这些异常的原因仍然未知。利用基因表达谱,我们试图确定可能与观察到的性腺变形相关的候选基因和生理过程,以便深入了解潜在的原因。利用原位合成的寡核苷酸阵列,我们比较了21,492个独特转录探针在性腺畸形和正常发育的雄性白鱼的肝脏和头部肾脏组织中的表达水平。这些鱼是在图恩湖两种遗传上截然不同的白鱼的产卵地点收集的。我们比较了56个个体的基因表达谱,即每个表型和每个群体的14个个体。逐基因分析显示正常和畸形鱼之间的表达差异较弱,在两种白鱼形态的畸形鱼头部肾组织中只发现了一个基因ictacalcin上调,但这种差异无法通过实时定量qPCR证实。生理过程水平的富集分析揭示了(i)两种组织中的免疫应答基因,特别是与肝脏补体激活相关的基因,(ii)肝脏中的蛋白质水解,(iii)头肾中的GTPase活性和Ras蛋白信号转导。与目前的文献相比,这种基因表达模式表明睾丸中存在慢性自身免疫性疾病。根据近年来对图恩湖浮游动物的摄食引起性腺畸形的观察,我们推测浮游生物在白鱼体内积累的一种外生菌引发自身免疫可能是导致性腺畸形的原因。我们提出了几种实验策略来验证或拒绝这一假设。
In 2000, fishermen reported the appearance of deformed reproductive organs in whitefish (Coregonus spp.) from Lake Thun, Switzerland. Despite intensive investigations, the causes of these abnormalities remain unknown. Using gene expression profiling, we sought to identify candidate genes and physiological processes possibly associated with the observed gonadal deformations, in order to gain insights into potential causes. Using in situ-synthesized oligonucleotide arrays, we compared the expression levels at 21,492 unique transcript probes in liver and head kidney tissue of male whitefish with deformed and normally developed gonads, respectively. The fish had been collected on spawning sites of two genetically distinct whitefish forms of Lake Thun. We contrasted the gene expression profiles of 56 individuals, i.e., 14 individuals of each phenotype and of each population. Gene-by-gene analysis revealed weak expression differences between normal and deformed fish, and only one gene, ictacalcin, was found to be up-regulated in head kidney tissue of deformed fish from both whitefish forms, However, this difference could not be confirmed with quantitative real-time qPCR. Enrichment analysis on the level of physiological processes revealed (i) the involvement of immune response genes in both tissues, particularly those linked to complement activation in the liver, (ii) proteolysis in the liver and (iii) GTPase activity and Ras protein signal transduction in the head kidney. In comparison with current literature, this gene expression pattern signals a chronic autoimmune disease in the testes. Based on the recent observations that gonad deformations are induced through feeding of zooplankton from Lake Thun we hypothesize that a xenobiotic accumulated in whitefish via the plankton triggering autoimmunity as the likely cause of gonad deformations. We propose several experimental strategies to verify or reject this hypothesis.
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