Intraflagellar transport-associated CCDC92 is required for spermiogenesis and male fertility in mice
Yue Lu, Xirui Zi, Qian Lyu, Qingchao Li, Hanxiao Yin, Yinghao Wang, Qijun Chen, Bin Kang, Shanshan Nai, Jun Zhou, Huijie Zhao, Ting Song
Abstract
The differentiation of a round spermatid into a streamlined sperm cell involves a series of remarkable morphological changes, such as sperm head shaping and flagellum formation. However, the underlying mechanism of spermatid shaping remains unclear. In this study, we find that CCDC92 deficiency in mice leads to severe abnormalities of the sperm head and flagellum and causes male infertility. Ultrastructural analyses of testicular elongating Ccdc92 knockout spermatids reveal severely deformed manchette structures. The manchette defects impair the subsequent sperm nucleus elongation and acrosome anchoring, resulting in misshapen rod-like nuclei and detached acrosomes. Molecularly, CCDC92 interacts with intraflagellar transport (IFT) complex components and colocalizes with IFT proteins at the manchette in developing spermatids. Quantitative proteomics further reveals the requirement of CCDC92 for proper flagellar distribution of axonemal microtubule inner proteins. Our findings demonstrate an essential role of CCDC92 in regulating spermatid shaping and provide novel insights into the pathology of male infertility.