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和多基物质通过向c-MYC来破坏小鼠胚胎的紧缩

Yanan Liu^1,2, Xianlei Jiang², Chenke Xu^1,2

¹Department of Environmental Science and Engineering, Fudan University, Shanghai 200433, China.

Environmental science & technology

|August 21, 2025

概括

和多基物质 (PFAS) 通过抑制c-MYC,一种关键蛋白质来破坏胚胎的早期发育. 这一发现解释了这些化学物质如何降低植入前胚胎的质量和紧缩.

科学领域:

环境毒理学
发育生物学
干细胞生物学

背景情况:

流行病学研究表明,和多基物质 (PFAS) 对植入前胚胎质量产生负面影响.
对PFAS对早期胚胎发育的影响的实验证据和机制理解有限.
胚胎在毛囊阶段的紧缩对于成功的发育至关重要.

研究的目的:

建立一个选平台来识别破坏胚胎紧缩的PFAS.
调查PFAS影响压缩的机制,重点是酸 (PFOA).
阐明c-MYC途径在PFAS诱导的发育性毒性的作用.

主要方法:

开发了一种表型查平台,使用小鼠扩大多能干细胞衍生的像毛囊的聚合物来评估紧缩.
选了19种PFAS以检测它们破坏聚合物循环性的能力.
在体外和体内研究了PFOA和c-MYC调节对粘附,细胞极性和胚胎质量的影响.

主要成果:

在选平台中发现了5种PFAS,特别是PFOA.
PFOA (100 nM) 抑制了粘附分子表达和细胞极性;在10 nM时,它减少了高质量的聚合物形成.
PFOA干扰了c- MYC/ MAX复合体的形成和转录活动,c- MYC的过度表达挽救了PFOA引起的损伤.

结论:

包括PFOA在内的PFAS可以破坏植入前胚胎的紧缩.
该机制涉及c- MYC介导的基因表达和细胞过程的抑制.
这项研究提供了关于PFAS暴露如何导致胚胎质量下降的机制见解.

关键词:

c-MYC 其他压缩方式扩展多能干细胞一个老鼠甲酸的使用

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