甲对生长激素的破坏作用与怀孕有关
Zongzhen Wu1, Long Ma1, Deqi Su1
1Key Laboratory of Special Environment and Health Research in Xinjiang, School of Public Health, Xinjiang Medical University, Urumqi, Xinjiang 830017, PR China.
Toxicology letters
|March 29, 2024
概括
怀孕期间甲基化物暴露通过改变生长激素 (GH) 途径,促进胚胎剂量依赖的生长. 这种效应是特定于怀孕,影响母亲的GH调节.
科学领域:
- 生殖毒理学 生殖毒理学
- 内分泌学 在内分泌学.
- 发展生物学 发展生物学
背景情况:
- 甲化物是一种常见的植物生长调节剂,导致广泛的饮食暴露.
- 之前的研究表明,怀孕期间甲暴露会增加胚胎大小和生长激素 (GH) 水平.
- 剂量反应关系和较低暴露水平的潜在机制仍然不清楚.
研究的目的:
- 调查甲在怀孕早期对胚胎生长和相关激素的剂量依赖性影响.
- 阐明甲化物影响胚胎发育和生长激素信号的机制.
- 为了确定甲对GH通路的影响是否与怀孕有关.
主要方法:
- 怀孕的老鼠从怀孕日0至11日口服了0.05,0.5和5毫克/体重千克的甲.
- 胚胎生长和生长激素 (GH),GH释放激素 (GHRH),体静止素 (SRIF) 和cAMP依赖蛋白激酶A (PKA) 信号的水平在妊娠11日被评估.
- 在怀孕和非怀孕的雌性大鼠之间进行了对GH和PKA通路反应的比较.
主要成果:
- 甲化物显著促进了胚胎的生长和发育,以剂量依赖的方式.
- 暴露增加了胚胎GH,GHGH和SRIF水平,同时抑制了胚胎PKA信号通路.
- 孕妇GH合成通过GHRH/SRIF-PKA-垂体特异转录因子1 (Pit-1) 途径进行调节;在非怀孕的老鼠中没有影响.
结论:
- 甲化物通过与怀孕相关的母体GH调节通路的改变来破坏胚胎的生长和发育.
- 观察到的效应是由GHRH/SRIF-PKA-Pit-1信号级联介导的,突出显示出怀孕特定的内分泌干扰.
- 这些发现强调了怀孕期间甲化物暴露的潜在风险.
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