产前暴露会通过改变Pdgfb促进体表观遗传修饰来破坏胎盘血管生成
Yu Zhang1, Ya-Ping Song1, Hong-Yan Wu1
1Department of Toxicology, Anhui Medical University, Hefei 230032, China.
Journal of hazardous materials
|May 29, 2025
概括
产前暴露会通过改变血小板衍生生长因子B (PDGFB) 的表观遗传编程来损害胎盘血管的发育. 补充α-谷氨酸 (α-KG) 可以防止这些有害影响.
科学领域:
- 环境健康 环境健康
- 生殖生物学 生殖生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 异常的胎盘与不良的怀孕和分娩结果有关.
- 产前暴露于环境毒素,如 (As),可能会破坏胎盘发育.
- 了解对胎盘血管生成的影响机制对于母婴健康至关重要.
研究的目的:
- 为了研究产前暴露对胎盘血管生成的影响.
- 阐明潜在的分子机制,专注于表观遗传调节.
- 探索潜在的干预措施,以减轻引起的胎盘损伤.
主要方法:
- 酸酸 (NaAsO2) 通过口服给孕小鼠,并使用HTR8/SVneo细胞进行体外研究.
- RNA测序以确定受影响的血管生成的关键调节者.
- 对DNA甲基化和基甲基化,TET酶活性和代谢学 (特别是α-甲酸盐) 的分析.
主要成果:
- 对的暴露减少了小鼠的胎盘血管性,并在试验室中损害了内皮细胞管的形成.
- 血小板衍生生长因子B (PDGFB) 被确定为由下调的关键调节器.
- 抑制了TET活性,导致PDGFB甲基化/基甲基化发生变化,并降低了α-甲酸水平;α-甲酸补充剂逆转了这些影响.
- 母体血清α-KG和胎盘PDGFB水平与尿有负相关,胎盘PDGFB与出生体重有正相关.
结论:
- 产前暴露会通过表观遗传改变PDGFB表达而损害胎盘血管生成.
- 对TET活性的抑制,可能是由于α-甲酸的减少,是一个关键的机制.
- α-甲酸盐补充剂有望改善对胎盘发育和胎儿生长的不良影响.
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