与精子中的暴露相关的转录和表观遗传变化
Xu Zhang1, Xiao-Rong Shen, Bin Wu
1Key Laboratory of Reproduction Regulation of National Health Commission, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, Shanghai 200032, China.
Asian journal of andrology
|January 13, 2026
概括
暴露于会通过改变精子基因表达和DNA甲基化来影响男性生育能力,特别是影响信号通路. 这可能导致精子质量和运动率下降.
科学领域:
- 生殖生物学 生殖生物学
- 环境毒理学环境毒理学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- (Pb) 暴露是男性不孕症的已知危险因素.
- 由于Pb暴露,精子中的转录和表观遗传变化尚未得到充分理解.
- 以前的研究将 (Ca) 恒温路径中的DNA甲基化变化与血中Pb水平升高的男性的精子运动性降低联系在一起.
研究的目的:
- 研究Pb暴露对人类精子中差异甲基基因 (DMG) 表达的影响.
- 分析与血液Pb水平相关的DNA甲基化和RNA丰度模式.
- 实验验证关键基因中不同甲基化区域的调节功能.
主要方法:
- 对六名男性的精液样本进行分析,根据血液中Pb含量 (0-2.5μg dl−1比5-10μg dl−1) 分类.
- 使用甲基化DNA免疫沉测序 (MeDIP-seq) 和RNA测序 (RNA-seq).
- 雇佣的双化酶记者测试验证了11个枢纽基因中不同甲基化区域的调控功能.
主要成果:
- 鉴定了低和高Pb暴露组之间的DNA甲基化和基因表达模式的显著差异.
- 在七个基因中显示出改变的促进子活性,包括通道子单元 (CACNA1H,CACNA1G,CACNA1I),CAMK2G,ATP2A3,SLC8A2和GRIN2D.
- 在信号通路基因表达的Pb暴露诱导的变化,特别是CACNA1H,SLC8A2和GRIN2D.
结论:
- 暴露显著改变了人类精子中的基因表达和DNA甲基化.
- 信号通路基因的变化,如CACNA1H,SLC8A2和GRIN2D,与Pb诱导的男性不孕症有关.
- 这些发现表明,潜在的分子机制将暴露与精子质量降低联系起来.
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