Global Gene Expression Profiling in Larval Zebrafish Exposed to Microcystin-LR and Microcystis Reveals Endocrine Disrupting Effects of Cyanobacteria
Global Gene Expression Profiling in Larval Zebrafish Exposed to Microcystin-LR and Microcystis Reveals Endocrine Disrupting Effects of Cyanobacteria
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DOI：
10.1021/es103538b
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发表时间：
2011-03-01
影响因子：
11.4
通讯作者：
Wilhelm, Steven W.
中科院分区：
文献类型：
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作者：
Rogers, Emily D.;Henry, Theodore B.;Wilhelm, Steven W.
微囊藻水华在世界范围内广泛发生，威胁着水生态系统和人类健康。亚致死对鱼类早期发育阶段的影响在很大程度上是未知的，研究主要集中在微囊藻毒素（如MC-LR），而不是微囊藻细胞。我们将斑马鱼幼虫暴露于纯化的MC-LR（0-1000 μ g/L）或含有4.5 μ g/L MC-LR的冻干铜绿微囊藻（Microcystis aeruginosa）中（96 h），并评估了全局基因表达的变化（Affytron GeneChip斑马鱼基因组阵列）。用Rosetta Resolver 7.0确定基因表达的显著变化（>= 1.7倍变化，p < 0.0001），并用大卫生物信息学工具进行本体分析。与对照组相比，差异表达基因的数量随着MC-LR浓度的增加而增加，包括与哺乳动物和鱼类老年阶段MC-LR已知作用机制相关的基因，以及斑马鱼幼鱼特有的基因。在暴露于微囊藻的幼虫中观察到卵黄蛋白原基因（vtg）的上调（在阵列上为19.2倍至>100倍;通过定量PCR证实为619.3倍），但在暴露于MC-LR的幼虫中未观察到。vtg的上调表明微囊藻暴露于雌激素样物质，提示微囊藻可能是环境雌激素的天然来源。对微囊藻水华影响的担忧可能超出了与微囊藻毒素相关的担忧。
Microcystis blooms occur worldwide and threaten aquatic ecosystems and human health. Sublethal effects on early developmental stages of fish are largely unknown, and research has mainly focused on microcystin toxins (such as MC-LR) rather than Microcystis cells. We exposed (96 h) zebrafish larvae to purified MC-LR (0-1000 mu g/L) or lyophilized Microcystis aeruginosa containing 4.5 mu g/L MC-LR and evaluated changes in global gene expression (Affymetrix GeneChip zebrafish genome arrays). Significant changes in gene expression (>= 1.7-fold change, p < 0.0001) were determined with Rosetta Resolver 7.0, and ontology analysis was conducted with the DAVID bioinformatics tool. The number of differentially expressed genes relative to control increased with MC-LR concentration and included genes related to known mechanisms of action for MC-LR in mammals and older life stages of fish, as well as genes unique to larval zebrafish. Up-regulation of vitellogenin genes (vtg) (19.2-fold to >100-fold on arrays; 619.3-fold confirmed by quantitative PCR) was observed in Microcystis-exposed larvae but not in larvae exposed to MC-LR. Up-regulation of vtg indicates exposure to estrogenic substance(s) and suggests that Microcystis may be a natural source of environmental estrogens. Concerns about effects of Microcystis blooms may extend beyond those associated with the microcystin toxin.