Zhou Yiling, Wang Yaling, Chen Jingwen, Wu Bangguo, Tang Shuyan, Zhang Feng, Liu Chunyu, Wang Lingbo
Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Institute of Reproduction and Development, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200433, China.
Basic Clin Androl. 2023 Nov 23;33(1):32. doi: 10.1186/s12610-023-00205-y.
The sperm flagellum is an evolutionarily conserved specialized organelle responsible for sperm motility and male fertility. Deleterious mutations in genes involved in the sperm flagellum assembly can often cause sperm motility defects and male infertility. The murine Dnali1 gene encodes a protein that is known to interact with the cytoplasmic dynein heavy chain 1.
A Dnali1-mutated mouse model was generated by inducing a nonsense mutation in the Dnali1 gene. The Dnali1-mutated male mice presented impaired sperm motility and were completely infertile. Although no obviously abnormal sperm morphology was observed in Dnali1-mutated male mice, the ultrastructural structure of sperm flagellum was disrupted, displaying as an asymmetrical distribution of the longitudinal columns (LCs). Notably, infertile Dnali1-mutated male mice were able to obtain offspring via ICSI.
Our results uncover a role of DNALI1 in sperm motility and male fertility in mice, and demonstrate that ICSI overcomes Dnali1-associated male infertility, thus providing guidance for the diagnosis and genetic counseling of DNALI1-associated human infertility.
精子鞭毛是一种在进化上保守的特殊细胞器，负责精子运动和男性生育能力。参与精子鞭毛组装的基因中的有害突变通常会导致精子运动缺陷和男性不育。小鼠Dnali1基因编码一种已知与细胞质动力蛋白重链1相互作用的蛋白质。
通过在Dnali1基因中诱导无义突变产生了Dnali1突变小鼠模型。Dnali1突变的雄性小鼠精子运动能力受损，完全不育。虽然在Dnali1突变的雄性小鼠中未观察到明显异常的精子形态，但精子鞭毛的超微结构被破坏，表现为纵柱（LCs）的不对称分布。值得注意的是，不育的Dnali1突变雄性小鼠能够通过卵胞浆内单精子注射（ICSI）获得后代。
我们的结果揭示了DNALI1在小鼠精子运动和男性生育中的作用，并证明ICSI克服了与Dnali1相关的男性不育，从而为与DNALI1相关的人类不育的诊断和遗传咨询提供指导。
