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终生暴露于十溴二苯乙烷(DBDPE)导致斑马鱼甲状腺内分泌系统的跨代表观遗传改变。

Life-time exposure to decabromodiphenyl ethane (DBDPE) caused transgenerational epigenetic alterations of thyroid endocrine system in zebrafish.

机构信息

Key Laboratory of Breeding Biotechnology and Sustainable Aquaculture, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China; State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.

Ecology and Environment Monitoring and Scientific Research Center, Ecology and Environment Administration of Yangtze River Basin, Ministry of Ecology and Environment, Wuhan 430010, China.

出版信息

Sci Total Environ. 2024 Nov 10;950:175337. doi: 10.1016/j.scitotenv.2024.175337. Epub 2024 Aug 6.

Abstract

Because of its ubiquitous occurrence in the environment, decabromodiphenyl ethane (DBDPE), a novel brominated flame retardant, has been widely concerned. However, its transgenerational thyroid disrupting potential and intricate mechanism are barely explored. Therefore, zebrafish embryos were exposed to environmentally relevant concentrations of DBDPE (0, 0.1, 1 and 10 nM) until sexual maturity. The results indicated that life-time exposure to DBDPE caused anxiety-like behavior in unexposed offspring. Furthermore, the changing of thyroid hormones as well as transcriptional and DNA methylation level in the promoter region of related genes were evaluated. The thyroid disruptions observed in F1 larvae were primarily attributed to excessive transfer of thyroid hormone from F0 adults to F1 eggs. Conversely, the disruptions in F2 larvae were likely due to inherited epigenetic changes, specifically hypomethylation of crh and hypermethylation of ugt1ab, passed down from the F1 generation. Additionally, our results revealed sex-specific responses of the hypothalamic-pituitary-thyroid (HPT) axis in adult zebrafish. Furthermore, thyroid disruptions observed in unexposed offspring were more likely inherited from their mothers. The current results prompted our in-depth understanding of the multi- and transgenerational toxicity by DBDPE, and also highlighted the need to consider their adverse effects on persistent and inheritable epigenetic changes in future research on emerging pollutants.

摘要

由于十溴二苯乙烷(DBDPE)在环境中普遍存在,作为一种新型溴系阻燃剂,已受到广泛关注。然而,其跨代甲状腺干扰潜力及其复杂的机制仍未得到充分探索。因此,本研究将斑马鱼胚胎暴露于环境相关浓度的 DBDPE(0、0.1、1 和 10 nM)直至性成熟。结果表明,终生暴露于 DBDPE 会导致未暴露后代出现焦虑样行为。此外,还评估了甲状腺激素的变化以及相关基因启动子区域的转录和 DNA 甲基化水平。F1 幼虫中观察到的甲状腺紊乱主要归因于 F0 亲鱼向 F1 卵中过量转移甲状腺激素。相反,F2 幼虫中的紊乱可能是由于从 F1 代遗传的表观遗传变化,特别是 crh 的低甲基化和 ugt1ab 的高甲基化。此外,我们的研究结果揭示了成年斑马鱼下丘脑-垂体-甲状腺(HPT)轴的性别特异性反应。此外,未暴露后代中观察到的甲状腺紊乱更可能来自其母亲。目前的研究结果促使我们深入了解 DBDPE 的多代和跨代毒性,并强调在未来对新兴污染物的研究中需要考虑其对持久性和可遗传性表观遗传变化的不利影响。

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