State Environmental Protection Key Laboratory of Environmental Risk Assessment and Control on Chemical Process, School of Resource and Environmental Engineering, East China University of Science and Technology, Shanghai 200237, China.
Branch of Shanghai, Yonker Environmental Protection Co., Ltd, Shanghai 200051, China.
Sci Total Environ. 2020 Feb 10;703:134920. doi: 10.1016/j.scitotenv.2019.134920. Epub 2019 Nov 1.
Tetrabromobisphenol A (TBBPA), one of the most common brominated flame retardants, has been associated with immunotoxicity, neurotoxicity, and reproductive toxicity. However, little attention has been focused on understanding the trans-generational effects of TBBPA. The present study used the Caenorhabditis elegans (C. elegans) animal model to evaluate the trans-generational effects of neurotoxicity induced by environmentally relevant concentrations of TBBPA (0, 0.1, 1, 10, 100, and 1000 µg/L). Multiple indicators including physiological effects (body length, brood size, head thrashes, body bends, and crawling trajectory), degree of neuronal damage (dopamine, GABAergic, and glutamatergic neurons), oxidative stress-related biochemical indicators (superoxide dismutase [SOD] activity, catalase [CAT] enzyme, malondialdehyde [MDA] production, and reactive oxygen species [ROS] accumulation), and stress-related gene expressions have been evaluated in the exposed parental C. elegans generation (G) and their progeny (G) under TBBPA-free conditions. The results showed that TBBPA exposure induced adverse effects on physiological endpoints, among which body bends and head thrashes were the most sensitive ones, detected above 1 µg/L in G and 100 µg/L in G nematodes, respectively. After contaminant exposure, the three neurons revealed damage related to neurobehavioral endpoints, with no hereditary effects in the progeny. The oxidative stress-related biochemical endpoints demonstrated that when the exposure concentrations were above 1 µg/L in maternal worms, impairment can be detected in both generations, but the progeny recovered at low toxicity concentration (1-100 µg/L). The integrated target gene expression profiles were clearly altered in G and G worms at concentrations between 1 and 1000 µg/L, and a more significant difference existed in two generations of nematodes at low levels (1-10 µg/L) of TBBPA. Studing trans-generational neurotoxicity and the underlying mechanism can generate a precise evaluation of the environmental risk of TBBPA.
四溴双酚 A（TBBPA）是最常见的溴化阻燃剂之一，与免疫毒性、神经毒性和生殖毒性有关。然而，人们对 TBBPA 的跨代效应知之甚少。本研究使用秀丽隐杆线虫（C. elegans）动物模型来评估环境相关浓度的 TBBPA（0、0.1、1、10、100 和 1000μg/L）引起的神经毒性的跨代效应。通过评估多个指标，包括生理效应（体长、产卵量、头部摆动、身体弯曲和爬行轨迹）、神经元损伤程度（多巴胺、GABA 能和谷氨酸能神经元）、氧化应激相关生化指标（超氧化物歧化酶[SOD]活性、过氧化氢酶[CAT]酶、丙二醛[MDA]产生和活性氧[ROS]积累）和应激相关基因表达，评估了暴露于 TBBPA 下的亲代 C. elegans 代（G）及其后代（G）的线虫。结果表明，TBBPA 暴露对生理终点有不良影响，其中身体弯曲和头部摆动是最敏感的，在 G 代线虫中 1μg/L 以上，在 G 代线虫中 100μg/L 以上可以检测到。污染物暴露后，三种神经元均显示与神经行为终点相关的损伤，但在后代中没有遗传效应。氧化应激相关的生化终点表明，当母体蠕虫的暴露浓度高于 1μg/L 时，两代均可检测到损伤，但在低毒性浓度（1-100μg/L）下，后代可恢复。在 1 至 1000μg/L 的浓度下，G 和 G 蠕虫的综合靶基因表达谱明显改变，在低浓度（1-10μg/L）的 TBBPA 下，两代线虫之间存在更显著的差异。研究跨代神经毒性及其潜在机制可以对 TBBPA 的环境风险进行精确评估。
