在子宫内, perfluorodecanoic 酸的暴露会导致胎儿的 Leydig 细胞功能障碍,通过内分泌网膜的压力介导的脂质组成改变
Zheyuan Ren1,2,3, Chengshuang Pan1,2,3,4, Yaoyao Dong5
1Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
Chemical research in toxicology
|January 15, 2025
概括
暴露在 perfluorodecanoic 酸 (PFDA) 中会损害胎儿的 Leydig 细胞,破坏的产生和男性生殖发育. 这项研究揭示了PFDAFDA.
科学领域:
- 环境毒理学环境毒理学
- 生殖生物学 生殖生物学
- 内分泌学 在内分泌学.
背景情况:
- perfluorodecanoic 酸 (PFDA) 是一种广泛存在的环境污染物.
- PFDA对胎儿莱迪格细胞 (FLC) 的生殖毒性及其机制尚不清楚.
研究的目的:
- 研究胎内PFDA暴露对胎儿莱迪格细胞功能和大鼠类固醇生成的影响.
- 阐明PFDA诱导的生殖毒性的潜在机制.
主要方法:
- 在关键的孕期期间,孕大鼠被暴露在不同剂量的PFDA (0.1,2.5,5毫克/公斤/天) 中.
- 分析了胎儿体重,血清丸激素水平以及与类固醇生成相关的基因/蛋白质表达.
- 评估了脂质代谢,内质网膜应激和莱迪格细胞分化标志物.
- 使用R2C莱迪格细胞和使用tauroursodeoxycholic acid (TUDCA) 的治疗进行了体外研究.
主要成果:
- 暴露于PFDA,特别是中剂量,增加了胎儿体重,但显著降低了血清丸激素水平.
- PFDA降低了参与类固醇生成的关键基因和蛋白质的调节 (Lhcgr,Star,Cyp11a1,Hsd3b1,Cyp17a1,Insl3).
- 高剂量的PFDA改变了脂质新陈代谢,诱导了细胞内膜网膜应激,并通过降低 Gli1.1 的调节抑制了胎儿的莱迪格细胞分化.
- 在体外,PFDA降低了的生物合成,这一效应被TUDCA扭转了.
结论:
- 暴露于PFDA会破坏胎儿老鼠丸脂代谢,并诱导内质网膜应激.
- PFDA干扰了类固醇生成网络,导致胎儿莱迪格细胞功能障碍和男性生殖发育受损.
- 这些发现凸显了PFDA对男性生殖健康的潜在环境风险.
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