Department of Andrology, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, China.
Fujian Provincial Key Laboratory of Reproductive Health Research, School of Medicine, Xiamen University, Xiamen, Fujian, China.
Front Endocrinol (Lausanne). 2023 Jan 16;13:1058651. doi: 10.3389/fendo.2022.1058651. eCollection 2022.
Asthenozoospermia is the most common cause of male infertility. Dynein protein arms play a crucial role in the motility of sperm flagella and defects in these proteins generally impair the axoneme structure and affect sperm flagella function. In this study, we performed whole exome sequencing for a cohort of 126 infertile patients with asthenozoospermia and identified homozygous mutation in one patient from a consanguineous family. This identified homozygous mutation was verified by Sanger sequencing. analysis showed that this homozygous mutation is very rare, highly pathogenic, and very conserved. Sperm routine analysis confirmed that the motility of the spermatozoa from the patient significantly decreased. Further sperm morphology analysis showed that the spermatozoa from the patient exhibited multiple flagella morphological defects and a specific loss in the inner dynein arms. Fortunately, the patient was able to have his child intracytoplasmic sperm injection treatment. Our study is the first to demonstrate that homozygous mutation may impair the integration of axoneme structure, affect sperm motility and cause asthenoteratozoospermia in human beings.
弱精症是男性不育症最常见的原因。动力蛋白臂在精子鞭毛的运动中起着至关重要的作用，这些蛋白质的缺陷通常会损害轴丝结构并影响精子鞭毛的功能。在这项研究中，我们对 126 名患有弱精症的不育患者进行了全外显子组测序，在一个近亲家庭的一名患者中发现了纯合突变。通过 Sanger 测序验证了该纯合突变。 分析表明，这种纯合突变非常罕见，高度致病性，且非常保守。精子常规分析证实，该患者精子的运动能力显著下降。进一步的精子形态分析显示，该患者的精子表现出多种鞭毛形态缺陷和内动力蛋白臂的特异性缺失。幸运的是，该患者能够通过胞浆内单精子注射治疗拥有自己的孩子。我们的研究首次证明，纯合 突变可能会损害轴丝结构的整合，影响精子的运动能力，并导致人类出现弱精畸形症。
