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：
因为它在环境中无处不在，十溴二苯基乙烷(DBDPE)，一种新型溴化阻燃剂，受到广泛关注。然而,它的跨代甲状腺破坏潜力和复杂的机制几乎没有探索。因此,将斑马鱼胚胎暴露于环境相关浓度的DBDPE（0、0.1、1和10nM）直至性成熟。结果表明，终身暴露于DBDPE会在未暴露的后代中引起焦虑样行为。此外，评价甲状腺激素的变化以及相关基因启动子区的转录和DNA甲基化水平。在F1幼虫中观察到的甲状腺破坏主要归因于甲状腺激素从F0成虫过度转移到F1卵。相反，F2幼虫的破坏可能是由于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，从F1一代传下来。此外,我们的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，在未暴露的后代中观察到的甲状腺功能破坏更有可能从其母亲那里遗传。目前的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它们对持久性和可遗传表观遗传变化的不利影响。
