对母性环境污染物和叶酸路径调节的计算洞察力
Adarsh Kumar Shukla1, Shadab Ahamad2, Prachi Kukshal1
1Department of Genomic Research, Sri Sathya Sai Sanjeevani Research Foundation, Palwal, Haryana 121102, India..
Reproductive toxicology (Elmsford, N.Y.)
|December 28, 2024
概括
母亲接触DDT和二氧化等环境毒素可以通过破坏叶酸通路来损害胎儿发育. 这项研究确定了关键的叶酸受体和载体作为目标,揭示了婴儿健康的重大风险.
科学领域:
- 环境毒理学环境毒理学
- 计算生物学是一种计算生物学.
- 发育生物学是发展生物学.
背景情况:
- 孕妇暴露于环境污染物会对胎儿的生长和发育产生负面影响.
- 关于环境毒素如何抑制叶酸通路内的关键标的研究有限.
研究的目的:
- 以计算方式识别母体环境毒素及其特定的分子标.
- 分析这些毒素对叶酸通路及其关键组成部分的抑制作用.
主要方法:
- 利用比较毒基因组学数据库 (CTD) 确定了27种母体环境毒素.
- 采用分子建模,对接和动力学模拟来分析毒素和叶酸通路蛋白之间的相互作用.
- 进行了毒性分析,以评估污染物对母亲健康和叶酸代谢的影响.
主要成果:
- 叶酸受体 (FOLR1,FOLR2,FOLR3) 和输送体 (SLC19A1,SLC46) 被确定为环境毒素的主要目标.
- FOLR3与包括二二三乙 (DDT),双和二氧化在内的有毒物质相互作用最强.
- 即使是最小的污染物暴露也会显著破坏叶酸代谢,影响母亲的健康,并可能导致胎儿形.
结论:
- 孕产妇的环境毒素严重阻碍叶酸通路,对胎儿发育构成严重风险.
- 特定的毒性物质对叶酸受体表现出强烈的抑制作用,特别是FOLR3.3.
- 了解这些相互作用对于减轻怀孕期间与环境污染相关的不良发育结果至关重要.
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