通过调节小鼠卵巢中Nrf2-介导的信号通路,暴露于Di-(2-乙烯基) 甲酸盐会诱导铁亡
Jinzhu Meng1, Lilin Xiao2, Qiuye Li2
1College of Veterinary Medicine, Hunan Agricultural University, Changsha, China; Guizhou Provincial Key Laboratory for Biodiversity Conservation and Utilization in the Fanjing Mountain Region, Tongren University, Tongren, China.
Ecotoxicology and environmental safety
|September 25, 2024
概括
通过诱导铁亡,暴露于二二乙烯甲酸盐 (DEHP) 会在小鼠中引起卵巢损伤. 这个过程由Nrf2信号通路调节,为治疗DEHP毒性的治疗策略提供了潜在的目标.
科学领域:
- 生殖毒理学 生殖毒理学
- 分子生物学分子生物学
- 内分泌学 在内分泌学.
背景情况:
- -2-乙烯基) 甲酸盐 (DEHP) 是一种在塑料中发现的内分泌干扰化学物质.
- DEHP显著影响女性生殖系统,但其在青春期前卵巢毒性的机制尚不清楚.
研究的目的:
- 在小鼠中阐明DEHP暴露引起的卵巢损伤的分子机制.
- 研究铁和Nrf2通路在DEHP诱导的卵巢毒性中的作用.
主要方法:
- 鼠被暴露在DEHP中,并评估了血清激素水平和卵巢形态.
- 卵巢转录组分析 (RNA-seq) 进行,以确定关键途径.
- 用铁亡标记物 (有色铁,MDA),西式斑点,免疫光和RNA干扰 (RNAi) 来验证卵巢组织和粒状细胞中的发现.
主要成果:
- 暴露于DEHP导致MEHP升高,卵巢激素 (E2,P4) 降低和卵巢损伤.
- RNA-seq揭示了铁灭相关基因的显著变化,可能由Nrf2调节.
- 观察到Nrf2稳定和核积累;Nrf2倒置加剧了铁,而ferrostatin-1治疗减弱了它.
结论:
- 在小鼠中,DEHP通过Nrf2介导的信号通路诱导卵巢铁亡.
- 这项研究为了解DEHP的生殖毒性提供了分子基础.
- 研究结果表明,对于减轻DEHP诱导的卵巢损伤的潜在治疗点.
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