转录基因分析揭示了甲基马和阿米对丸发育的甲状腺激素介导和化合物特异性影响
Ida W Strand1, Monica K Draskau1, Sofie Frank Rising1
1National Food Institute, Technical University of Denmark, Kgs. Lyngby, DK-2800, Denmark.
概括
甲状腺激素因MMI或小鼠中的阿米暴露而受到干扰,导致丸基因表达发生显著变化. 转录学确定了共享和化合物特异性的效应,揭示了对低甲状腺诱导的丸干扰的分子见解.
科学领域:
- 内分泌学 在内分泌学.
- 毒理学 毒理学 毒理学
- 发展生物学 发展生物学
背景情况:
- 甲状腺激素 (THs) 对于丸正常发育至关重要.
- 暴露于甲状腺氧化酶 (TPO) 抑制化学物质,如MMI和阿米,可以诱导甲状腺功能低下,并损害子发育在动物.
- 这些影响背后的分子机制尚未完全理解,这阻碍了化学风险评估.
研究的目的:
- 为了研究在发育期暴露于TPO抑制化学物质MMI和阿米后,大鼠丸的分子变化.
- 为了识别与甲状腺功能低下症引起的丸干扰相关的共享和化合物特定的转录组形状.
- 评估转录组学在检测丸早期毒理效应方面的有用性.
主要方法:
- 怀孕的斯普拉格-道利大鼠在怀孕期间和幼早期发育期间暴露在MMI或阿米中.
- 在怀孕21日和产后16天收集了测试,以使用BRB-seq.进行转录基因分析.
- 进行了差异基因表达分析,以确定基因表达模式的变化.
主要成果:
- 无论是MMI还是阿米暴露都显著改变了丸转录组,特别是在出生后的第16天.
- 确定了313个差异表达基因 (DEGs) 的共享配置文件,表明了常见的TH介导效应.
- 阿米暴露单独影响了1517个DEGs,表明除了TH干扰之外的化合物特异性毒理作用.
结论:
- 转录形状分析是一种敏感的方法,用于检测由导致甲状腺功能低下的化学物质暴露引起的早期丸干扰.
- 该研究确定了在正在发育的丸中MMI和阿米特罗尔暴露的共同和独特的分子特征.
- 这些发现为改进化学风险评估策略提供了有价值的分子洞察力,补充了传统的基因病学终点.
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