Parental Co-Exposure to Methylmercury and Inorganic Arsenic in Zebrafish (Danio rerio): Metabolism and Offspring Behavior

斑马鱼（斑马鱼）父母同时接触甲基汞和无机砷：代谢和后代行为

• 批准号: 10352116
• 负责人: Sarah E Rothenberg
• 金额: $ 39.27万
• 依托单位: OREGON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10352116
• 关键词: Ablation; Adolescent; Adult; Age; Arsenic; Attention; Behavior; Biological; Biological Models; Blood Pressure; Brain; Carcinogens; Chemicals; Child; Development; Diet; Embryo; Environment; Enzymes; Exposure to; Eye; Female; Fertilization; Fetal Growth; Frequencies; Gills; Health; Heavy Metals; Homologous Gene; Hour; Human; Inductively Coupled Plasma Mass Spectrometry; Intestines; Joints; Kidney; Lasers; Link; Liver; Malignant neoplasm of liver; Malignant neoplasm of lung; Malignant neoplasm of prostate; Malignant neoplasm of urinary bladder; Mercury; Metabolic syndrome; Metabolism; Metals; Methionine; Methylation; Methylmercury Compounds; Methyltransferase; Modeling; Molecular; Morphology; Motor; Muscle; Muscle Tonus; Natural regeneration; Neuraxis; Neurocognitive Deficit; Neurotoxins; Organ; Outcome; Performance; Poison; Process; Rattus; Renal carcinoma; Research Personnel; S-Adenosylmethionine; Sex Differences; Signal Pathway; Site; Skin; Skin Cancer; Statistical Methods; Tissues; Toxic effect; Visuospatial; Water; Zebrafish; base; cytotoxic; disease registry; epidemiology study; exposed human population; fetal; genome-wide; genotoxicity; in vitro Model; male; methylmercury exposure; neurobehavioral; neurodevelopment; neurotoxic; neurotoxicity; offspring; postnatal; prenatal; sex; sodium arsenite; synergism; transcriptome sequencing; transcriptomics; treatment group; uptake

Summary Methylmercury (MeHg) is a potent neurotoxin, and recent studies indicate that inorganic arsenic(III) (iAs) is also neurotoxic. Although chemicals co-occur in the environment, the study of chemical mixtures is more recent. Heavy metals target the central nervous system, and co-exposure may result in synergistic neurotoxic impacts. However, the biological and molecular mechanisms underlying these joint effects are uncertain. The aim of our study is to investigate synergism between iAs and MeHg, using the zebrafish (Danio rerio) model system. Aim 1. Investigate the uptake and metabolism of iAs and MeHg in zebrafish. We anticipate that co-exposure to both chemicals will alter the proportion of arsenic species in the liver, compared to controls. Adult zebrafish will be exposed to environmentally relevant levels of MeHg (through diet) and sodium arsenite (through water) (six treatment groups). In the liver, mercury species and arsenic species will be compared between treatment groups, and sex-specific differences will be investigated. Accumulation of mercury and arsenic in adult tissues and organs will be visualized using laser ablation-ICP-MS. Aim 2. Determine the impacts of MeHg and iAs exposure in progeny, including neurobehavioral outcomes, and mechanisms of toxicity. Mercury and arsenic species will be determined in whole embryos [120 hours post fertilization (hpf)], exposed to both neurotoxicants through maternal transfer. In embryos (6-120 hpf) and adults [90 days post fertilization (dpf)], morphological and neurobehavioral endpoints will be assessed. Using RNA sequencing, we will conduct genome-wide transcriptomics of offspring brains (90 dpf), and identify signaling pathways, which are enriched or depleted due to co-exposure. Transcriptomic results will be compared between treatment groups and males/females. This study will advance our understanding of the mechanisms by which co-exposure to two chemicals, which frequently co-occur in the environment, contribute synergistically to offspring neurotoxicity.

概括 甲基汞 (MeHg) 是一种强效神经毒素，最近的研究表明无机砷 (III) (iAs) 也具有神经毒性。尽管化学物质同时存在于环境中，但对化学混合物的研究仍在进行中。 最近的。重金属以中枢神经系统为目标，同时接触可能会产生协同作用 神经毒性影响。然而，这些联合效应背后的生物和分子机制是 不确定。我们研究的目的是利用斑马鱼 (Danio rerio）模型系统。目标 1. 研究斑马鱼对 iAs 和 MeHg 的吸收和代谢。我们 预计同时接触这两种化学物质会改变肝脏中砷形态的比例 来控制。成年斑马鱼将暴露于环境相关水平的甲基汞（通过饮食）并且 亚砷酸钠（通过水）（六个处理组）。在肝脏中，汞和砷会 在治疗组之间进行比较，并将调查性别差异。累积 成人组织和器官中的汞和砷将使用激光烧蚀-ICP-MS 进行可视化。目标2。 确定甲基汞和无机砷暴露对后代的影响，包括神经行为结果，以及 毒性机制。将测定整个胚胎中的汞和砷形态 [120 小时后 受精（hpf）]，通过母体转移暴露于两种神经毒物。在胚胎（6-120 hpf）和成人中 [受精后 90 天 (dpf)]，将评估形态学和神经行为终点。使用RNA 测序后，我们将对后代大脑进行全基因组转录组学 (90 dpf)，并识别信号传导 途径，由于共同暴露而丰富或耗尽。将比较转录组结果 治疗组和男性/女性之间。这项研究将加深我们对机制的理解 通过同时暴露于环境中经常同时出现的两种化学物质，有助于 对后代的神经毒性具有协同作用。