暴露于BPA会通过扰乱Wnt/β-catenin通路而影响小鼠的胃体轴延长
Paola Rebuzzini1, Serena Rustichelli2,3, Lorenzo Fassina4,5
1Laboratory of Biology and Biotechnology of Reproduction, Department of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, Via Ferrata 9, 27100 Pavia, Italy.
International journal of molecular sciences
|July 27, 2024
概括
像 Bisphenol A (BPA) 这样的环境毒素会损害哺乳动物胚胎的发育. 通过破坏Wnt/β-catenin信号传递和细胞分化,BPA暴露阻止了胃体轴延长.
科学领域:
- 发育生物学是发展生物学.
- 毒理学 毒理学 毒理学
- 干细胞研究的研究.
背景情况:
- 哺乳动物胚胎对环境有毒物质 (ETs) 很敏感.
- 双甲 (BPA) 是一种广泛存在的ET,具有内分泌干扰性,影响生殖.
- BPA对植入周围胚胎发育的影响在很大程度上是未知的.
研究的目的:
- 使用胃类模型研究BPA暴露对早期胚胎发育的影响.
- 阐明BPA诱导的胃类动物发育停滞背后的分子机制.
主要方法:
- 利用基于3D干细胞的体外模型,以模仿早期胚胎发育.
- 在Wnt/β-catenin通路激活期间暴露于BPA的胃类动物.
- 分析了与细胞粘附,多能性和分化有关的基因和蛋白质表达的变化.
主要成果:
- 在Wnt/β-catenin激活过程中暴露于BPA导致了胃状轴延长的停止.
- 这种停止与降低的β-catenin蛋白水平有关.
- 观察到Snail,Slug,Twist和N-cadherin的下调,以及Oct4,T/Bra和Cdx2的改变表达.
- 从多能性退出障碍以及随后BPA暴露细胞的分化有助于发育缺陷.
结论:
- 通过扰乱Wnt/β-catenin信号传输,BPA抑制了胃体轴延长.
- 减少N-cadherin表达和改变关键发育基因的表达 (Oct4,T/Bra,Cdx2) 导致胃类细胞发育受损.
- 胃类动物作为一种有价值的模型,用于研究环境毒素对哺乳动物早期发育的有害影响.
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