Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
Department of Veterinary Biomedical Sciences and Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan S7N5B3, Canada.
Environ Pollut. 2018 Oct;241:540-548. doi: 10.1016/j.envpol.2018.05.024. Epub 2018 May 22.
Frequencies and durations of blooms of cyanobacteria are increasing. Some cyanobacteria can produce cyanotoxins including microcystins (MCs). MCs are the most common toxic products of hazardous algal blooms (HABs), with the greatest potential for exposure and to cause toxicity. Recently, MCs have been shown to disrupt endocrine functions. In this study, for the first time, effects of MC-LR on the hypothalamic-pituitary-inter-renal (HPI) axis during early embryonic development (embryos/larvae) of zebrafish (Danio rerio), were investigated. Embryos/larvae of zebrafish were exposed to 1, 10, 100, or 300 μg MC-LR/L during the period of 4-168 h post-fertilization (hpf). Exposure to 300 μg MC-LR/L resulted in significantly greater concentrations of whole-body cortisol than those in controls. Expressions of genes along the HPI axis and mineralocorticoid receptor (MR-) and glucocorticoid receptor (GR-) centered gene networks were evaluated by use of quantitative real-time PCR. Expression of mRNA for crh was significantly down-regulated by exposure to 300 μg MC-LR/L, while expressions of crhbp, crhr1, and crhr2 were significantly up-regulated, relative to controls. MC-LR caused significantly lesser levels of mRNA for steroidogenic genes including hmgra, star, and cyp17, but expression of mRNA for hsd20b was significantly greater than that of controls. Treatment with MC-LR also altered profiles of transcription of MR- and GR-centered gene networks, which might result in multiple responses. Taken together, these results demonstrated that MC-LR affected the corticosteroid-endocrine system of larvae of zebrafish. This study provided valuable insights into molecular mechanisms behind potential toxicity and endocrine disruption of MCs.
蓝藻水华的频率和持续时间正在增加。一些蓝藻可以产生蓝藻毒素,包括微囊藻毒素(MCs)。MCs 是有害藻类水华(HABs)中最常见的有毒产物,具有最大的暴露和毒性潜力。最近,MCs 已被证明会破坏内分泌功能。在这项研究中,首次研究了 MC-LR 对斑马鱼(Danio rerio)早期胚胎发育(胚胎/幼鱼)下丘脑-垂体-肾间(HPI)轴的影响。在受精后 4-168 小时(hpf)期间,将胚胎/幼鱼暴露于 1、10、100 或 300μg MC-LR/L 中。暴露于 300μg MC-LR/L 导致全身皮质醇浓度明显高于对照组。通过定量实时 PCR 评估沿 HPI 轴和盐皮质激素受体(MR-)和糖皮质激素受体(GR-)为中心的基因网络的基因表达。暴露于 300μg MC-LR/L 导致 crh 的 mRNA 表达显著下调,而 crhbp、crhr1 和 crhr2 的表达则显著上调,与对照组相比。MC-LR 导致类固醇生成基因(包括 hmgra、star 和 cyp17)的 mRNA 水平显著降低,但 hsd20b 的 mRNA 表达显著高于对照组。MC-LR 处理还改变了 MR-和 GR-为中心的基因网络的转录谱,这可能导致多种反应。总之,这些结果表明 MC-LR 影响了斑马鱼幼鱼的皮质甾醇内分泌系统。本研究为 MC 潜在毒性和内分泌干扰的分子机制提供了有价值的见解。