在ZCWPW1中,一种功能丧失的变异会导致人类男性不孕症,伴有精子头缺陷和高DNA碎片化
Yuelin Song1,2, Juncen Guo2,3, Yanling Zhou2,3
1Department of Obstetrics and Gynaecology, West China Second University Hospital, Sichuan University, Chengdu, 610041, China.
Reproductive health
|February 3, 2024
概括
在人类患者中,ZCWPW1基因的新型同卵性突变导致男性不孕症. 这种遗传变异导致精子缺陷,包括头部异常和DNA碎片化增加,有助于oligoasthenoteratozoospermia.
科学领域:
- 遗传学 是一个遗传学.
- 生殖生物学 生殖生物学
- 人类分子遗传学 人类分子遗传学
背景情况:
- 男性不孕症是一个重大的全球健康问题,需要进一步调查致病基因.
- 确立了ZCWPW1基因在雄性小鼠生育中的重要作用,但其在人类生殖中的功能需要澄清.
研究的目的:
- 研究ZCWPW1在人类男性不孕症中的作用.
- 为了确定与oligoasthenoteratozoospermia相关的ZCWPW1中的遗传变异.
主要方法:
- 整体外体和桑格测序用于识别不育患者的基因变异.
- 现型分析包括帕帕尼科劳染色,免疫光和电子显微镜.
- 在体外实验中评估了ZCWPW1变异的致病性及其对DNA修复的影响.
主要成果:
- 在一个患有橄酸和精子头缺陷的患者中发现了同卵性ZCWPW1误解突变 (c.1064C>T,p.P355L).
- 这种突变导致ZCWPW1的表达减少和DNA修复能力受损,由增加的DNA碎片化证明.
- 在体外研究证实了突变ZCWPW1对细胞DNA完整性的有害影响.
结论:
- 这项研究报告了ZCWPW1中第一个同卵性误解突变,导致人类男性不孕.
- 鉴定到的ZCWPW1变体与精子头缺陷和高DNA碎片化有关,有助于化精子.
- 这一发现扩大了已知的男性不孕症遗传原因的范围.
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