US Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Mid-Continent Ecology Division, 6201 Congdon Blvd., Duluth, MN, USA, 55804, USA.
Aquat Toxicol. 2009 Dec 13;95(4):258-72. doi: 10.1016/j.aquatox.2008.08.021. Epub 2008 Sep 19.
The objectives of this study were to characterize gene expression responses to hypoxia in gonads of mature zebrafish (Danio rerio), and to start characterizing modes of action by which hypoxia could potentially alter reproduction. Adult male and female zebrafish were maintained under normoxia (7mgO(2)/L), moderate hypoxia (3mgO(2)/L), and severe hypoxia (1mgO(2)/L) for 4 and 14 days and changes in gene expression in gonadal tissues (n=5 per sex per treatment) were evaluated using a commercial 21,000 gene zebrafish oligonucleotide microarray. Differentially expressed genes were determined using ANOVA (p<0.05), and enriched gene ontology (GO) categories (p<0.01) identified using GeneSpring GX software. Short-term (4d) exposure to hypoxia affected expression of genes associated with the initial adaptive responses such as: metabolism of carbohydrates and proteins, nucleotide metabolism, haemoglobin synthesis, reactive oxygen species metabolism, and locomotion. Prolonged (14d) hypoxia affected a suite of genes belonging to different GO categories: lipid metabolism, reproduction (e.g., steroid hormone synthesis), and immune responses. Results of the present study demonstrate that reproduction likely would be affected by hypoxia via multiple modes of action. These include previously hypothesized mechanisms such as modulation of expression of steroidogenic genes, and downregulation of serotonergic pathway. In addition, we propose that there are multiple other points of disruption of reproductive system function linked, for example, to reorganization of lipid transport and other mechanisms involved in responding to hypoxia (e.g., hydroxysteroid dehydrogenase alterations, downregulation of contractile elements, etc.).
本研究的目的是描述成熟斑马鱼(Danio rerio)性腺中对缺氧的基因表达反应,并开始描述缺氧可能通过哪些方式改变生殖功能。将成年雄性和雌性斑马鱼分别在常氧(7mgO2/L)、中度缺氧(3mgO2/L)和严重缺氧(1mgO2/L)条件下维持 4 天和 14 天,然后使用商用的 21,000 个基因斑马鱼寡核苷酸微阵列评估性腺组织中基因表达的变化(每个处理组每个性别 5 个样本)。使用 GeneSpring GX 软件通过 ANOVA(p<0.05)确定差异表达基因,并通过富集基因本体论(GO)类别(p<0.01)确定差异表达基因。短期(4d)缺氧暴露会影响与初始适应反应相关的基因的表达,例如:碳水化合物和蛋白质代谢、核苷酸代谢、血红蛋白合成、活性氧代谢和运动。长期(14d)缺氧会影响属于不同 GO 类别的一整套基因:脂质代谢、生殖(例如类固醇激素合成)和免疫反应。本研究的结果表明,生殖功能可能会受到缺氧的多种作用方式的影响。这些作用方式包括先前假设的机制,例如调节类固醇生成基因的表达,以及下调 5-羟色胺能途径。此外,我们提出,与脂质转运和其他参与应对缺氧的机制(例如羟甾体脱氢酶改变、收缩元件下调等)有关的生殖系统功能的多个其他破坏点。