在RNA结合蛋白ADAD2中的双基突变会导致人类的精子生成失败和非阻断性亚精
Baolu Shi1, Wasim Shah1, Li Liu2
1Division of Reproduction and Genetics, First Affiliated Hospital of USTC, School of Basic Medical Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China, Hefei, China.
Human reproduction open
|June 16, 2023
概括
ADAD2基因的突变会通过破坏人类和小鼠的精子发育,导致非阻塞性精症 (NOA). 圆形精液注射 (ROSI) 显示出治疗受影响小鼠不孕症的前景.
科学领域:
- 遗传学 是一个遗传学.
- 生殖生物学 生殖生物学
- 不孕症研究 不孕症研究
背景情况:
- 非阻塞性精子缺血症 (NOA) 是男性不孕症的一种严重形式.
- 缺陷的精子生成导致精子在射精中缺失.
- 在人类NOA中ADAD2突变的作用需要进一步的功能验证.
研究的目的:
- 在NOA患者中识别致病突变.
- 为了研究ADAD2突变对精子生成的影响.
- 在小鼠模型中验证发现并探索潜在的治疗方法.
主要方法:
- 整体外因子测序在NOA患者中发现了ADAD2突变.
- 在CRISPR/Cas9生成的Adad2突变小鼠中.
- 定量PCR,西式涂抹和免疫光检测评估了蛋白质表达和局部化.
- 圆形精子注射 (ROSI) 使用突变小鼠圆形精子进行.
主要成果:
- 在巴基斯坦的NOA家族中发现了三种衰退的ADAD2突变 (MT1,MT2,MT3).
- 突变减少了ADAD2的表达,并导致人类和小鼠的精子发生失败.
- 由于ADAD2蛋白质的不稳定性,Adad2突变小鼠表现出精子生成缺陷.
- 在Adad2小鼠中,ROSI产生了正常发育和生育能力的活力后代.
结论:
- ADAD2基因突变具有病原性,在人类和小鼠中引起一致的精子生成缺陷.
- ROSI是一种潜在的辅助生殖技术,用于治疗ADAD2相关的男性不孕症.
- 研究结果为有关ADAD2相关不孕症的遗传咨询提供了见解.
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