双甲基甲酸通过NDRG1通过准PPARα:RXRα来破坏 trofhoblast功能和脂质代谢
Yu Zhang1, Yanqing Geng2, Yan Zhang1
1Department of Health Toxicology, School of Public Health, Chongqing Medical University, Chongqing 400016, PR China; Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing 400016, PR China.
Toxicology
|March 29, 2025
概括
家庭灰尘中的二环基甲酸盐 (DCHP) 通过破坏脂质代谢和细胞功能来损害胎盘发育. 针对NDRG1可能会提供针对DCHP的策略.
科学领域:
- 环境毒理学环境毒理学
- 生殖生物学 生殖生物学
- 细胞的新陈代谢
背景情况:
- 酸盐 (PAE) 是已知的环境污染物,对怀孕结果产生负面影响.
- 双环基甲酸盐 (DCHP) 是城市尘埃中普遍存在的PAE,但其对胎盘发育的具体影响尚不清楚.
研究的目的:
- 研究DCHP对热囊细胞功能和胎盘发育的影响.
- 阐明DCHP生殖毒性的潜在分子机制.
主要方法:
- 在试验室中,人体 trofhoblast 细胞 (HTR-8/SVneo) 暴露于 DCHP.
- 孕妇小鼠在体内暴露于DCHP.
- 评估脂质滴积累,线粒体功能,细胞迁移和入侵.
- 基因敲除N-myc下游调节基因1 (NDRG1) 的基因.
- 对PPARα:RXRα转录活动的分析.
主要成果:
- 暴露于DCHP导致胎盘脂质液滴积累,并使胎儿体内体重增加.
- 在体外,DCHP诱导脂肪酸吸收,脂质积累,线粒体功能障碍,并抑制了 trofhoblast 细胞迁移和入侵.
- NDRG1倒置减轻了DCHP诱导的脂质异常,并恢复了细胞功能.
- DCHP增强了PPARα:RXRα的转录活性,促进了NDRG1的转录.
结论:
- DCHP通过代谢失调扰乱了热囊细胞功能和胎盘发育.
- PPARα:RXRα/NDRG1通路是调解DCHP毒性的关键分子机制.
- 这些发现提供了关于DCHP的生殖风险和潜在的治疗点的见解.
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