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Tcte1淘汰对能量链运输和精子生成的影响:对男性不孕不育的影响

Marta Olszewska¹, Agnieszka Malcher¹, Tomasz Stokowy²

¹Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.

Human reproduction open

|April 23, 2024

概括

通过破坏精子功能和分子网络,TCTE1基因突变导致男性不育. 这项研究证明了TCTE1.

科学领域:

遗传学和生殖生物学
分子和细胞生物学分子和细胞生物学

背景情况:

轴膜dynein臂基因的突变会导致不育男性的精子异常.
对于精子鞭状体的打击至关重要的nexin-dynein调节复合体 (N-DRC) 是由DRC1-DRC7蛋白组装在一起的.
DRC5 (TCTE1) 已被涉及到异常的精子鞭子殴打,但其确切的作用仍然不清楚.

研究的目的:

调查TCTE1突变在男性不孕症中的因果作用.
阐明TCTE1相关的男性生殖功能衰竭背后的分子机制.

主要方法:

使用CRISPR/Cas9技术生成了一个TCTE1基因淘汰赛小鼠模型.
在淘汰赛小鼠中评估生殖潜力,精液特征,丸基因表达 (RNA-seq),精子ATP水平和亡.
在人类不育男性的队列中选TCTE1变异.

主要成果:

同性卵性TCTE1淘汰赛的雄性在有类动物精子症的情况下是不育的;异性卵性雄性在有类动物精子症的情况下表现出有类动物精子不足.
TCTE1突变影响了参与ATP生产,亡和精子生成的基因的表达,导致精子ATP水平降低和精子尾部形态异常.
罕见的TCTE1变体预测是致病的,在6.05%的不育男性中被发现,这表明它在人类男性不育中发挥了作用.

结论:

TCTE1基因在精子生成和精子功能中发挥着关键作用,其突变是导致男性不孕症的原因.
TCTE1突变破坏丸分子网络,导致男性生殖功能衰竭.
应该承认TCTE1是与男性不孕症相关的重要基因.

关键词:

费图布·费图布 (Fetube Fetub) 是一个在MMAF中,MMAF是MMAF.在 N-DRC 中.在 TCTE1 里面.简单的说来,是没有足够的.男人的不孕不育症.mt-Co2 2 的使用量.果酸和酸的作用是什么?精子线粒体和精子线粒体精子运动性精子运动性

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