Atrazine (ATZ), a commonly used pesticide linked to endocrine disruption, cancer, and altered neurochemistry, frequently contaminates water sources at levels above the US Environmental Protection Agency’s 3 parts per billion (ppb; μg/L) maximum contaminant level. Adult male zebrafish behavior, brain transcriptome, brain methylation status, and neuropathology were examined to test the hypothesis that embryonic ATZ exposure causes delayed neurotoxicity, according to the developmental origins of health and disease paradigm. Zebrafish (Danio rerio) embryos were exposed to 0 ppb, 0.3 ppb, 3 ppb, or 30 ppb ATZ during embryogenesis (1–72 h post fertilization (hpf)), then rinsed and raised to maturity. At 9 months post fertilization (mpf), males had decreased locomotor parameters during a battery of behavioral tests. Transcriptomic analysis identified altered gene expression in organismal development, cancer, and nervous and reproductive system development and function pathways and networks. The brain was evaluated histopathologically for morphometric differences, and decreased numbers of cells were identified in raphe populations. Global methylation levels were evaluated at 12 mpf, and the body length, body weight, and brain weight were measured at 14 mpf to evaluate effects of ATZ on mature brain size. No significant difference in genome methylation or brain size was observed. The results demonstrate that developmental exposure to ATZ does affect neurodevelopment and neural function in adult male zebrafish and raises concern for possible health effects in humans due to ATZ’s environmental presence and persistence.

Graphical abstract

阿特拉津 (ATZ) 是一种与内分泌紊乱、癌症和神经化学改变有关的常用杀虫剂，其污染水源的水平经常超过美国环境保护署规定的十亿分之三 (ppb; μg/L) 最大污染水平。根据健康和疾病的发育起源范式，对成年雄性斑马鱼的行为、脑转录组、脑甲基化状态和神经病理学进行了检查，以检验胚胎 ATZ 暴露导致延迟神经毒性的假设。斑马鱼（斑马鱼) 胚胎在胚胎发生过程中（受精后 1-72 小时 (hpf)）暴露于 0 ppb、0.3 ppb、3 ppb 或 30 ppb ATZ，然后冲洗并培养至成熟。在受精后 9 个月 (mpf)，男性在一系列行为测试中运动参数降低。转录组分析确定了生物体发育、癌症、神经和生殖系统发育以及功能通路和网络中基因表达的改变。在组织病理学上评估了大脑的形态学差异，并在中缝种群中发现了减少的细胞数量。以 12 mpf 评估整体甲基化水平，并以 14 mpf 测量体长、体重和脑重，以评估 ATZ 对成熟大脑大小的影响。没有观察到基因组甲基化或大脑大小的显着差异。

图形概要