Data from: Early life exposure to low levels of AHR agonist PCB126 (3,3’,4,4’,5-pentachlorobiphenyl) reprograms gene expression in adult brain

Early life exposure to environmental chemicals can have long-term consequences that are not always apparent until later in life. We recently demonstrated that developmental exposure of zebrafish to low, non-embryotoxic levels of 3,3’,4,4’,5-pentachlorobiphenyl (PCB126) did not affect larval behavior, but caused changes in adult behavior. The objective of this study was to investigate the underlying molecular basis for adult behavioral phenotypes resulting from early life exposure to PCB126. We exposed zebrafish embryos to PCB126 during early development and measured transcriptional profiles in whole embryos, larvae and adult male brains using RNA-sequencing. Early life exposure to 0.3 nM PCB126 induced cyp1a transcript levels in 2-dpf embryos, but not in 5-dpf larvae, suggesting transient activation of aryl hydrocarbon receptor with this treatment. No significant induction of cyp1a was observed in the brains of adults exposed as embryos to PCB126. However, a total of 2209 and 1628 genes were differentially expressed in 0.3 nM and 1.2 nM PCB126-exposed groups, respectively. KEGG pathway analyses of upregulated genes in the brain suggest enrichment of calcium signaling, MAPK and notch signaling, and lysine degradation pathways. Calcium is an important signaling molecule in the brain and altered calcium homeostasis could affect neurobehavior. The downregulated genes in the brain were enriched with oxidative phosphorylation and various metabolic pathways, suggesting that the metabolic capacity of the brain is impaired. Overall, our results suggest that PCB exposure during sensitive periods of early development alters normal development of the brain by reprogramming gene expression patterns, which may result in alterations in adult behavior.

生命早期暴露于环境化学物可引发长期健康影响，此类影响往往直至生命后期才会显现。我们此前的研究证实，斑马鱼（zebrafish）在发育阶段暴露于低剂量、无胚胎毒性的3,3’,4,4’,5-五氯联苯（3,3’,4,4’,5-pentachlorobiphenyl，PCB126）时，并不会影响幼鱼行为，但会改变成鱼的行为模式。本研究旨在探究生命早期暴露于PCB126所引发的成鱼行为表型的潜在分子机制。我们在斑马鱼胚胎发育早期对其施加PCB126暴露处理，并通过RNA测序（RNA-sequencing）检测了完整胚胎、幼鱼以及成年雄鱼脑组织的转录组谱。生命早期暴露于0.3 nM的PCB126可在受精后2天（2-dpf）的胚胎中诱导cyp1a转录本水平升高，但在受精后5天（5-dpf）的幼鱼中未出现该现象，提示该处理可短暂激活芳香烃受体（aryl hydrocarbon receptor）。在胚胎期暴露于PCB126的成年斑马鱼脑组织中，未检测到cyp1a的显著诱导表达。然而，0.3 nM与1.2 nM PCB126暴露组中分别有2209个和1628个基因呈现差异表达。对脑组织中上调基因的京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes，KEGG）通路富集分析显示，钙信号通路、丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）信号通路、Notch信号通路（notch signaling）以及赖氨酸降解通路均出现富集。钙是脑中重要的信号分子，钙稳态失衡可影响神经行为。脑组织中下调基因则富集于氧化磷酸化及多种代谢通路，提示脑部代谢能力受到损伤。综上，本研究结果表明，在早期发育的敏感窗口期暴露于PCB，可通过重编程基因表达模式改变脑部正常发育过程，进而可能导致成鱼行为发生改变。