典型抗生素父/母代暴露对子代免疫毒性及机理研究

抗生素广泛的使用使其源源不断地排放到水生生态系统，导致鱼类长期处于低剂量、种类繁多的抗生素暴露中，致使其能在鱼类亲代中富集从而可能影响其子代的生长发育和功能活动。然而，国内外关于抗生素对鱼类子代的毒性研究还鲜有报道，尤其免疫毒性研究十分少见。本项目将以模式生物斑马鱼为研究对象，筛选出环境中最常检出的5种抗生素，环境浓度下单一和混合暴露亲代斑马鱼，分析抗生素在亲代和子代体内的富集情况，评价抗生素在鱼体的代际效应；同时检测对子代生长发育系统和免疫系统相关指标的影响，全面评价抗生素暴露对鱼体子代的发育毒性效应。再结合转录组测序、经典通路分析以及受体抑制技术验证转录组学预测的经典通路，探明抗生素暴露造成鱼类子代免疫系统损伤的作用机理。免疫系统是鱼类抵抗外界环境污染最重要的保卫系统，阐明抗生素对斑马鱼子代的发育免疫毒性效应，对保障鱼群繁育及生态系统健康具有重要的意义。

Frequent and widespread use of antibiotics causes their continuous release into the aquatic ecosystem, leading to fish being uninterruptedly exposed to a wide variety of antibiotics although at a low dose. As a result, the antibiotics may be enriched in the parental fish and transferred to their offspring, resulting in the toxicity on growth, development, and functional activities. However, there are few reports on the toxicity of antibiotics in fish offspring, especially on immunotoxicity. Therefore, this study is designed to evaluate developmental immunotoxicity in zebrafish offspring after parental exposure to environmentally relevant concentrations of 5 most common antibiotics and their mixtures. We will quantify the “paternal/maternal transfer effects” of antibiotics in zebrafish by analyzing the enrichment of antibiotics in the parents’ major organs and the embryos of their offspring. Moreover, the relevant parameters including the immune related genes and protein expression, immune cells formation and function and antibacterial ability will be analyzed in order to identify the effects of antibiotic exposure on developmental immunotoxicity in zebrafish offspring. In addition, we will combine global transcriptome sequencing (RNA-Seq), canonical pathway analysis and pathway receptor inhibition techniques (receptor antagonist and morpholino technique) to explore and validate the mechanism of immunotoxicity in the zebrafish offspring after parental exposure to antibiotics. Since the immune system is the most important defense system for fish against environmental pollution, it is of great significance for fish reproduction and conservation to investigate immunotoxicity of antibiotics in zebrafish offspring.