Oligoasthenoteratospermia (OAT), characterized by abnormally low sperm count, poor sperm motility, and abnormally high number of deformed spermatozoa, is an important cause of male infertility. Its genetic basis in many affected individuals remains unknown. Here, we found that CCDC157 variants are associated with OAT. In two cohorts, a 21‐bp (g.30768132_30768152del21) and/or 24‐bp (g.30772543_30772566del24) deletion of CCDC157 were identified in five sporadic OAT patients, and 2 cases within one pedigree. In a mouse model, loss of Ccdc157 led to male sterility with OAT‐like phenotypes. Electron microscopy revealed misstructured acrosome and abnormal head–tail coupling apparatus in the sperm of Ccdc157‐null mice. Comparative transcriptome analysis showed that the Ccdc157 mutation alters the expressions of genes involved in cell migration/motility and Golgi components. Abnormal Golgi apparatus and decreased expressions of genes involved in acrosome formation and lipid metabolism were detected in Ccdc157‐deprived mouse germ cells. Interestingly, we attempted to treat infertile patients and Ccdc157 mutant mice with a Chinese medicine, Huangjin Zanyu, which improved the fertility in one patient and most mice that carried the heterozygous mutation in CCDC157. Healthy offspring were produced. Our study reveals CCDC157 is essential for sperm maturation and may serve as a marker for diagnosis of OAT.

中文翻译：

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CCDC157 对于精子分化至关重要，并在男性中显示出与少弱精子症相关的突变

少弱精子症（OAT）以精子数量异常低、精子活力差、畸形精子数量异常多为特征，是男性不育的重要原因。许多受影响个体的遗传基础仍然未知。在这里，我们发现中央疾病预防控制中心157变体与 OAT 相关。在两个队列中，在 5 名散发性 OAT 患者以及一个家系中的 2 例患者中发现了 21 bp (g.30768132_30768152del21) 和/或 24 bp (g.30772543_30772566del24) 的 CCDC157 缺失。在小鼠模型中，损失中央结算公司157导致具有类似燕麦表型的雄性不育。电子显微镜显示精子顶体结构错误和头尾耦合装置异常中央结算公司157‐无效小鼠。比较转录组分析表明中央结算公司157突变改变了参与细胞迁移/运动和高尔基体成分的基因的表达。检测到高尔基体异常以及顶体形成和脂质代谢相关基因表达减少中央结算公司157‐剥夺小鼠生殖细胞。有趣的是，我们尝试治疗不孕患者中央结算公司157突变小鼠服用中药黄金瓒玉，改善了一名患者的生育能力，并且大多数携带杂合突变的小鼠中央疾病预防控制中心157。产生了健康的后代。我们的研究表明 CCDC157 对于精子成熟至关重要，并且可以作为诊断 OAT 的标记物。