Richter Catherine A, Martyniuk Christopher J, Annis Mandy L, Brumbaugh William G, Chasar Lia C, Denslow Nancy D, Tillitt Donald E
U.S. Geological Survey, Columbia Environmental Research Center, 4200 New Haven Road, Columbia, MO 65201, USA.
Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611, USA.
Gen Comp Endocrinol. 2014 Jul 1;203:215-224. doi: 10.1016/j.ygcen.2014.03.029. Epub 2014 Mar 30.
Methyl-mercury (MeHg) is a potent neuroendocrine disruptor that impairs reproductive processes in fish. The objectives of this study were to (1) characterize transcriptomic changes induced by MeHg exposure in the female largemouth bass (LMB) hypothalamus under controlled laboratory conditions, (2) investigate the health and reproductive impacts of MeHg exposure on male and female largemouth bass (LMB) in the natural environment, and (3) identify MeHg-associated gene expression patterns in whole brain of female LMB from MeHg-contaminated habitats. The laboratory experiment was a single injection of 2.5 μg MeHg/g body weight for 96 h exposure. The field survey compared river systems in Florida, USA with comparably lower concentrations of MeHg (Wekiva, Santa Fe, and St. Johns Rivers) in fish and one river system with LMB that contained elevated concentrations of MeHg (St. Marys River). Microarray analysis was used to quantify transcriptomic responses to MeHg exposure. Although fish at the high-MeHg site did not show overt health or reproductive impairment, there were MeHg-responsive genes and pathways identified in the laboratory study that were also altered in fish from the high-MeHg site relative to fish at the low-MeHg sites. Gene network analysis suggested that MeHg regulated the expression targets of neuropeptide receptor and steroid signaling, as well as structural components of the cell. Disease-associated gene networks related to MeHg exposure, based upon expression data, included cerebellum ataxia, movement disorders, and hypercalcemia. Gene responses in the CNS are consistent with the documented neurotoxicological and neuroendocrine disrupting effects of MeHg in vertebrates.
甲基汞(MeHg)是一种强效的神经内分泌干扰物,会损害鱼类的生殖过程。本研究的目的是:(1)在可控的实验室条件下,描述甲基汞暴露诱导的雌性大口黑鲈(LMB)下丘脑转录组变化;(2)调查甲基汞暴露对自然环境中雄性和雌性大口黑鲈(LMB)健康和生殖的影响;(3)识别来自甲基汞污染栖息地的雌性LMB全脑中与甲基汞相关的基因表达模式。实验室实验为单次注射2.5μg甲基汞/克体重,暴露96小时。实地调查比较了美国佛罗里达州鱼类中甲基汞浓度相对较低的河流系统(韦基瓦河、圣菲河和圣约翰斯河)以及一个大口黑鲈体内甲基汞浓度升高的河流系统(圣玛丽斯河)。利用微阵列分析来量化对甲基汞暴露的转录组反应。尽管高甲基汞位点的鱼类未表现出明显的健康或生殖损害,但实验室研究中鉴定出的甲基汞反应基因和途径,在高甲基汞位点的鱼类中相对于低甲基汞位点的鱼类也发生了改变。基因网络分析表明,甲基汞调节神经肽受体和类固醇信号的表达靶点以及细胞的结构成分。基于表达数据,与甲基汞暴露相关的疾病相关基因网络包括小脑共济失调、运动障碍和高钙血症。中枢神经系统中的基因反应与文献记载的甲基汞对脊椎动物的神经毒理学和神经内分泌干扰作用一致。