在子宫内接触双A和S的环境相关剂量会破坏跨代的生殖细胞编程,由单核多基因组解决
Liang Zhao1,2, Mingxin Shi1, Sarayut Winuthayanon3
1School of Molecular Biosciences, Center for Reproductive Biology, Washington State University, 1770 NE Stadium Way, Pullman, WA, 99164, USA.
Environmental health perspectives
|June 3, 2025
概括
产前接触双A (BPA) 和双S (BPS) 减少了三代小鼠的精子数量. 这些内分泌干扰化学物质改变了生殖细胞表观遗传学,长期影响了生殖健康.
科学领域:
- 生殖毒理学 生殖毒理学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 环境健康 环境健康
背景情况:
- 像双A (BPA) 这样的内分泌干扰化学物质 (EDC) 可以在几代人中破坏繁殖.
- 胚胎细胞的表观遗传变化是这些跨代缺陷的拟议机制.
- 以前的研究表明,BPA/BPS暴露导致生殖功能障碍和小鼠精子的表观遗传变化.
研究的目的:
- 系统地阐明由产前BPA和BPS暴露引起的生殖缺陷的跨代遗传机制.
- 分析从F1到F3代的小鼠生殖系中的转录和表观遗传变化.
- 了解BPA和BPS的影响是如何跨世代持续的.
主要方法:
- 怀孕的小鼠 (F0) 接受了口服BPA或BPS (0.5-1000μg/kg/天).
- 在成年男性后代 (F1-F3) 中评估了精子数量和运动性.
- 单核多组组 (snRNA-seq和snATAC-seq) 在新生儿精子 (F1-F3) 上进行,剂量为50μg/kg/day.
主要成果:
- 在F1-F3世代中,BPA和BPS暴露减少了精子数量.
- 暴露破坏了精子细胞群平衡,并改变了促进体中的染色质可访问性.
- 关键的转录因子动机 (SP1,SP4,DMRT1) 显示活性升高,DMRT1在几代人中持续升高.
- 在F1中,BPA具有更强的基因表达效应,而BPS则显示出更持久的效应.
结论:
- 产前BPA/BPS暴露会改变生殖线染色质可访问性和转录因子活性.
- 这些表观遗传变化有助于破坏精子转录和减少精子数量,持续到F3代.
- 这项研究提供了BPA/BPS暴露后第一个对跨代基因和染色质动态的系统分析.
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