Knecht Andrea L, Truong Lisa, Marvel Skylar W, Reif David M, Garcia Abraham, Lu Catherine, Simonich Michael T, Teeguarden Justin G, Tanguay Robert L
Department of Environmental and Molecular Toxicology, The Sinnhuber Aquatic Research Laboratory, Environmental Health Sciences Center, Oregon State University, Corvallis, OR, USA.
Department of Biological Sciences, Bioinformatics Research Center, Center for Human Health and the Environment, North Carolina State University, Raleigh, NC, USA.
Toxicol Appl Pharmacol. 2017 Aug 15;329:148-157. doi: 10.1016/j.taap.2017.05.033. Epub 2017 Jun 3.
Benzo[a]pyrene (B[a]P) is a well-known genotoxic polycylic aromatic compound whose toxicity is dependent on signaling via the aryl hydrocarbon receptor (AHR). It is unclear to what extent detrimental effects of B[a]P exposures might impact future generations and whether transgenerational effects might be AHR-dependent. This study examined the effects of developmental B[a]P exposure on 3 generations of zebrafish. Zebrafish embryos were exposed from 6 to 120h post fertilization (hpf) to 5 and 10μM B[a]P and raised in chemical-free water until adulthood (F0). Two generations were raised from F0 fish to evaluate transgenerational inheritance. Morphological, physiological and neurobehavioral parameters were measured at two life stages. Juveniles of the F0 and F2 exhibited hyper locomotor activity, decreased heartbeat and mitochondrial function. B[a]P exposure during development resulted in decreased global DNA methylation levels and generally reduced expression of DNA methyltransferases in wild type zebrafish, with the latter effect largely reversed in an AHR2-null background. Adults from the F0 B[a]P exposed lineage displayed social anxiety-like behavior. Adults in the F2 transgeneration manifested gender-specific increased body mass index (BMI), increased oxygen consumption and hyper-avoidance behavior. Exposure to benzo[a]pyrene during development resulted in transgenerational inheritance of neurobehavioral and physiological deficiencies. Indirect evidence suggested the potential for an AHR2-dependent epigenetic route.
苯并[a]芘（B[a]P）是一种著名的具有基因毒性的多环芳烃化合物，其毒性取决于芳烃受体（AHR）介导的信号传导。目前尚不清楚B[a]P暴露的有害影响在多大程度上可能影响后代，以及跨代效应是否可能依赖于AHR。本研究检测了发育过程中暴露于B[a]P对三代斑马鱼的影响。斑马鱼胚胎在受精后6至120小时（hpf）暴露于5和10μM的B[a]P，并在无化学物质的水中饲养至成年（F0）。从F0代鱼繁育出两代以评估跨代遗传。在两个生命阶段测量了形态、生理和神经行为参数。F0和F2代的幼鱼表现出运动活动亢进、心跳减慢和线粒体功能下降。发育过程中暴露于B[a]P导致野生型斑马鱼的整体DNA甲基化水平降低，DNA甲基转移酶的表达普遍减少，在AHR2基因缺失的背景下，后一种效应在很大程度上得到逆转。来自F0代暴露于B[a]P品系的成鱼表现出社交焦虑样行为。F2代的成鱼表现出特定性别的体重指数（BMI）增加、耗氧量增加和过度回避行为。发育过程中暴露于苯并[a]芘导致神经行为和生理缺陷的跨代遗传。间接证据表明存在依赖于AHR2的表观遗传途径的可能性。
