Scott Department of Urology, Baylor College of Medicine, Houston, TX 77030, USA
Department of Surgery, Texas Children's Hospital, Houston, TX 77030, USA.
Development. 2021 Jan 13;148(1):dev191189. doi: 10.1242/dev.191189.
Cryptorchidism is the most common urologic birth defect in men and is a predisposing factor of male infertility and testicular cancer, yet the etiology remains largely unknown. microdeletions and microduplications contribute to cryptorchidism, infertility and testicular tumors. Although deletion or overexpression in mice causes spermatogenic failure, the mechanism by which influences testicular function is unknown. This investigation revealed that null mice develop cryptorchidism with severe gubernacular defects and progressive loss of germ cells resulting in infertility and, in rare cases, testicular tumors. It was hypothesized that germ cell depletion resulted from an increase in WNT4 levels. To test this hypothesis, the phenotype of a double-null mouse model lacking both and in germ cells was analyzed. Double-null mice are fertile. This finding indicates that germ cell maintenance is dependent on repression of , supporting a role for in germ cell survival. In the future, modulation of expression in men with cryptorchidism and spermatogenic failure due to copy number variations may provide a novel approach to improve their spermatogenesis and perhaps their fertility potential after orchidopexy.
隐睾症是男性中最常见的泌尿生殖系统先天缺陷，也是男性不育和睾丸癌的一个致病因素，但病因仍很大程度上未知。微缺失和微重复导致隐睾症、不育和睾丸肿瘤。尽管 缺失或过表达在小鼠中导致精子发生失败，但 影响睾丸功能的机制尚不清楚。本研究表明，缺失 小鼠发生隐睾症，伴严重提睾肌缺陷和生殖细胞进行性丧失，导致不育，极少数情况下发生睾丸肿瘤。据推测，生殖细胞耗竭是由于 WNT4 水平升高所致。为了验证这一假说，分析了缺失 和 的双缺失小鼠模型的表型。双缺失小鼠具有生育能力。这一发现表明，生殖细胞的维持依赖于 对 的抑制作用，支持 在生殖细胞存活中的作用。将来，由于 拷贝数变异导致隐睾症和精子发生失败的男性中 的表达调节，可能为改善其精子发生，也许在隐睾固定术后提高其生育能力提供一种新方法。
