产前乙氨基暴露对胎儿长骨发育的毒性影响取决于过程,剂量和阶段
Chi Ma1, Xufeng Li1, Hao Xiao2
1Division of Joint Surgery and Sports Medicine, Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
Toxicology letters
|September 23, 2023
概括
在小鼠中产前乙氨基暴露 (PAcE) 通过减少生长和延迟骨化,损害胎儿长骨发育. 这种发育性毒性,特别是在高剂量和怀孕中期时,可能涉及Wnt信号通路.
科学领域:
- 发展性毒理学 发展性毒理学
- 骨生物学 骨生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 乙氨基是怀孕期间广泛使用的止痛药.
- 流行病学研究将产前乙氨基暴露 (PAcE) 与不良后代结果联系起来.
- 对PAcE对胎儿长骨发育的具体影响及其机制尚不清楚.
研究的目的:
- 研究PAcE对小鼠胎儿长骨发育的影响.
- 探索潜在的机制,包括基因表达和信号通路.
主要方法:
- 在不同剂量,频率和妊娠阶段给母亲服用乙氨基后,分析了胎儿小鼠的股骨.
- 测量包括股骨的长度,初级骨化中心 (POC) 的发展和矿物化.
- 评估了骨质生成标记物和Wnt信号通路组件的基因表达.
主要成果:
- PAcE显著减少了大腿骨的长度和POC的发展,延迟了矿化和骨化.
- 骨质基因表达 (Runx2, Bsp, Ocn, Col1a1) 的下调.
- 骨质细胞和血管功能也受到抑制,效果在高剂量,多次暴露和怀孕中期最明显.
- 规范Wnt信号通路的变化与骨质生成的变化相关.
结论:
- PAcE诱导发育性毒性,并损害胎儿长骨中的多细胞功能.
- 高剂量,多次暴露和怀孕中期的使用构成最大的风险.
- 正规的Wnt信号通路可能会调解PAcE观察到的发育毒性.
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