齐普罗夫洛克萨通过通过NR4A1通路下调STAR表达来破坏小鼠的丸激素合成
Lirui Hou1, Yuhan Fu1, Yue Zhao1
1College of Food Science and Nutritional Engineering, China Agricultural University, 17 Qinghua East Road, Haidian District, Beijing 100083, China.
Ecotoxicology and environmental safety
|June 24, 2025
概括
在青少年小鼠中,通过影响NR4A1/StAR通路,普洛素 (CIP) 暴露显著降低了丸激素的产生. 低剂量CIP证明了对男性生殖健康的内分泌干扰作用.
科学领域:
- 内分泌学 在内分泌学.
- 毒理学 毒理学 毒理学
- 生殖生物学 生殖生物学
背景情况:
- 齐普洛素 (CIP) 是一种广泛使用的类抗生素.
- 奎诺隆被怀疑是内分泌干扰剂,但CIP对生命早期丸激素产生的影响尚不清楚.
研究的目的:
- 在青少年雄性小鼠中研究普洛素对丸激素合成的毒性作用.
- 阐明CIP诱导的丸激素抑制背后的分子机制.
主要方法:
- 青少年雄性小鼠被暴露在CIP (1-75毫克/公斤) 的不同剂量中30天.
- 在体外研究中使用了小鼠丸细胞系 (TM3,TM4,GC-2spd).
- 技术包括西方抹杀,qPCR,分子对接和转录基因测序.
主要成果:
- 低剂量CIP (1 mg/kg) 降低了血清丸激素和增加了LH/FSH水平.
- 暴露于CIP减少了精子数量,导致丸损伤,并在体外抑制了细胞活动.
- 通过降低NR4A1的调节,CIP抑制了STAR蛋白的表达,阻断了丸激素的合成.
结论:
- 齐普罗夫洛克萨通过NR4A1/StAR途径抑制丸激素合成,作为内分泌干扰剂.
- 早期暴露于CIP,特别是低剂量暴露,对男性生殖健康构成重大风险.
- 调查结果强调,在广泛使用CIP方面需要谨慎.
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