新型CYLC1变异与男性不孕症有关,原因是精子头形
Kexin Yu1, Yu Wang1, Xiaoya Zhu1
1Reproductive Medicine Center, Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, Anhui, China.
Journal of assisted reproduction and genetics
|October 11, 2025
概括
在患有精子头形的不孕男性中发现了新的CYLC1基因变异. 这些CYLC1变异改变了精子结构和功能,影响了男性的生育能力,但通过细胞内质精子注射 (ICSI) 实现了成功怀孕.
科学领域:
- 遗传学和基因组学 遗传学和基因组学
- 生殖生物学 生殖生物学
- 分子生物学分子生物学
背景情况:
- 男性不孕症影响了大量寻求生殖援助的夫妇.
- 精子头变形是男性因子不孕症的常见原因之一.
- 目前尚不完全了解CYCLIN C1 (CYLC1) 基因对男性生育能力的作用.
研究的目的:
- 在不孕男性中识别新型CYCLIN C1 (CYLC1) 变异,这些男性呈现精子头形.
- 研究已识别的CYLC1变异对精子形态和蛋白质定位的功能影响.
- 评估CYLC1在男性生育能力中的作用,使用淘汰赛小鼠模型.
主要方法:
- 整体外体测序 (WES) 和桑格测序用于识别不育个体中的CYLC1变异.
- 精子形态被评估使用Hematoxylin-eosin (HE) 染色.
- 蛋白质表达和局部化通过西式涂抹和免疫光检测进行了评估.
- 使用CRISPR/Cas9进行功能研究,生成了一个CYLC1淘汰赛 (KO) 鼠标模型.
- 扫描电子显微镜 (SEM) 和传输电子显微镜 (TEM) 用于精子的超结构分析.
主要成果:
- 在患有精子头形的不孕男性中发现了两种新的CYLC1变异 (c.982A>G:p.K328E和c.971A>T:p.K324M).
- 虽然蛋白质表达水平没有受到影响,但精子中的CYLC1和PLCZ1局部发生了变化,以及体形态.
- Cylc1-KO小鼠表现出亚生育性,其特征是精子中的宏核脱离.
- 在两名男性中,通过细胞内质精子注射 (ICSI) 实现了成功怀孕.
结论:
- 已识别的CYLC1变异扩大了与男性不孕症相关的已知遗传因素的范围.
- 这些发现提供了进一步的证据,将CYLC1变异与精子头形和男性生育能力受损联系起来.
- 该研究强调了ICSI在CYLC1相关不孕症的情况下实现怀孕的潜力.
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