精子发生障碍疾病严重影响人类生殖健康，主要由精子发生或成熟障碍引起。精子发生在生精小管内进行， IV型胶原蛋白为其基底膜主要成分，可水解释放NC1片段。过表达NC1多肽可以引起Sertoli细胞（SC）骨架功能异常，破坏SC体外屏障，其具体机制需进一步研究。我们前期发现，大鼠SC过表达NC1后Cdc42的活性升高，而Cdc42失活可以抑制NC1引起的SC屏障功能降低；此外，在Adjudin引起的生精障碍模型中，NC1显著升高。为此，我们拟在本研究中通过失活型Cdc42处理NC1过表达的SC，检测SC屏障及细胞骨架功能等相关指标变化，以明确Cdc42在NC1调节BTB中的作用。此外，我们拟检测生精障碍动物模型及临床生精障碍睾丸样本中NC1水平及Cdc42活性改变；建立NC1基因敲入大鼠，检测其生精功能变化并分析Cdc42在其中的作用。期待进一步明确NC1影响BTB功能及精子发生的分子机制。

Spermatogenic disorders have a serious impact on human reproductive health and are mainly caused by disorders in spermatogenesis or maturation. Spermatogenesis occurs in the seminiferous tubules, and type IV collagen is the main component of its basement membrane, which can be hydrolyzed and release the NC1 domain. Overexpression of NC1 polypeptide can cause abnormal skeletal function of Sertoli cells (SC) and destroy the barrier of SC in vitro, while the specific mechanism requires further study. We have previously found that the activity of Cdc42 was increased after the overexpression of NC1 in rat SC, while the inactivation of Cdc42 inhibited the reduction of SC barrier function induced by NC1. Moreover, the level of NC1 was significantly enhanced in the model of spermatogenic disorder induced by Adjudin. Therefore, in this study we intend to treat NC1-overexpressed SC with inactive Cdc42 and detect the changes in SC barrier and cytoskeletal function, in order to clarify the roles of Cdc42 in the regulation of BTB by NC1. In addition, we intend to detect the changes in NC1 level and Cdc42 activity in testicular samples from animal models and clinical patients with spermatogenic disorders, and establish NC1-knock in transgenic rats to detect the changes in their spermatogenic function and analyze the role of Cdc42 involved. We expect to further understand the molecular mechanism of the influence of NC1 on BTB function and spermatogenesis.