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在人类和小鼠中,IQUB突变诱导了辐射1缺陷,导致有正常精子形态的精子和精子
Tingwenyi Hu1,2, Xiangrong Tang1,2, Tiechao Ruan3,4
1Chongqing Key Laboratory of Human Embryo Engineering and Precision Medicine, Center for Reproductive Medicine, Women and Children's Hospital of Chongqing Medical University, Chongqing, 400010, China.
Cell communication and signaling : CCS
|January 24, 2025
概括
在IQUB中发生的基因突变会通过影响精子鞭状辐射1组件引起精 (ASZ). 内细胞质精子注射 (ICSI) 可以有效治疗这种男性不孕症.
科学领域:
- 生殖生物学 生殖生物学
- 人类遗传学 人类遗传学
- 分子细胞生物学 分子细胞生物学
背景情况:
- 精子精症 (ASZ) 是男性不孕症的主要原因,通常与影响精子鞭毛功能的遗传因素有关.
- 射线螺杆 (RSs) 是调节精子运动的关键宏分子复合体,但许多组成部分仍然没有表征.
- 了解ASZ的遗传基础对于开发有效的生育治疗至关重要.
研究的目的:
- 为了研究IQUB基因突变在ASZ中的作用.
- 在哺乳动物精子中识别辐射1 (RS1) 复合体的关键组成部分.
- 探索IQUB缺陷背后的病理机制及其对精子功能的影响.
主要方法:
- 在323名患有ASZ.的不育男性队伍中进行全外测序.
- 使用计算机辅助分析,帕帕尼科劳染色和电子显微镜进行精子分析 (运动性,形态,超结构).
- 蛋白质组和生物信息分析以确定RS1组件和模型IQUB的功能;ICSI用于治疗评估.
主要成果:
- 在一个ASZ患者中发现了一种新的同卵性IQUB突变 (c.842del),导致IQUB完全丧失和RS1缺乏.
- 在人类患者和Iqub-/-小鼠中,IQUB缺乏会影响精子运动和RS1组合.
- 确定了RS1的12个关键组成部分,IQUB缺乏与内部二联因臂 (DNAH7,DNAH12) 的下调有关.
结论:
- 在人类和小鼠中,IQUB作为精子鞭状RS1的适配器.
- 在IQUB中发生的基因突变与正常精子形态的生精子症有因果关系.
- 这项研究扩展了已知的男性不孕不育的遗传原因,并强调ICSI是可行的治疗方法.
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