The phenotypic and transcriptomic effects of developmental exposure to nanomolar levels of estrone and bisphenol A in zebrafish.

The phenotypic and transcriptomic effects of developmental exposure to nanomolar levels of estrone and bisphenol A in zebrafish.
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DOI:
10.1016/j.scitotenv.2020.143736
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发表时间:
2021-02-25
期刊:
The Science of the total environment
影响因子:
--
通讯作者:
Baker TR
Baker TR
中科院分区:
其他
文献类型:
--
作者:
Wu CC;Shields JN;Akemann C;Meyer DN;Connell M;Baker BB;Pitts DK;Baker TR

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雌酮和双酚A是两种内分泌干扰物(EDCs),预计其效力低于雌激素,如17β-雌二醇和17α-炔雌醇。人体暴露于雌酮和BPA的浓度可以低至纳摩尔水平。然而,很少有毒理学研究关注纳摩尔剂量效应。低水平的内分泌干扰物可能会导致非单调反应。此外,不同发育阶段的暴露可导致不同的健康结果。为了确定雌酮和BPA的纳摩尔剂量效应,我们使用斑马鱼建模来研究从受精后0 - 5天(dpf)延长持续时间暴露和受精后4 - 5天短期暴露后的表型和转录组学反应。我们发现,非单调的转录组反应发生后,在1 nM的雌酮或BPA的长期曝光。在这个水平上,雌酮也会导致斑马鱼的运动行为减退。在长时间和短期暴露后,BPA导致更明显的表型反应,即骨骼异常和运动变化,以及比雌酮暴露更显著的转录组反应。短期暴露后,浓度等于或高于100 nM的BPA会影响运动行为,并改变与神经系统疾病相关的雌激素和非雌激素基因的表达。这些数据提供了神经基因表达和相关的表型反应之间的差距,由于雌酮或BPA暴露的机制。该研究也为评估BPA和雌酮在水生环境中的可接受浓度提供了见解。
Estrone and BPA are two endocrine disrupting chemicals (EDCs) that are predicted to be less potent than estrogens such as 17β-estradiol and 17α-ethinylestradiol. Human exposure concentrations to estrone and BPA can be as low as nanomolar levels. However, very few toxicological studies have focused on the nanomolar-dose effects. Low level of EDCs can potentially cause non-monotonic responses. In addition, exposures at different developmental stages can lead to different health outcomes. To identify the nanomolar-dose effects of estrone and BPA, we used zebrafish modeling to study the phenotypic and transcriptomic responses after extended duration exposure from 0 – 5 days post-fertilization (dpf) and short-term exposure at days 4 – 5 post fertilization. We found that non-monotonic transcriptomic responses occurred after extended duration exposures at 1 nM of estrone or BPA. At this level, estrone also caused hypoactivity locomotive behavior in zebrafish. After both extended duration and short-term exposures, BPA led to more apparent phenotypic responses, i.e. skeletal abnormalities and locomotion changes, and more significant transcriptomic responses than estrone exposure. After short-term exposure, BPA at concentrations equal or above 100 nM affected locomotive behavior and changed the expression of both estrogenic and non-estrogenic genes that are linked to neurological diseases. These data provide gaps of mechanisms between neurological genes expression and associated phenotypic response due to estrone or BPA exposures. This study also provides insights for assessing the acceptable concentration of BPA and estrone in aquatic environments.
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