Sperm motility is crucial for successful fertilization. Highly decorated doublet microtubules (DMTs) form the sperm tail skeleton, which propels the movement of spermatozoa. Using cryo-electron microscopy (cryo-EM) and artificial intelligence (AI)-based modeling, we determined the structures of mouse and human sperm DMTs and built an atomic model of the 48-nm repeat of the mouse sperm DMT. Our analysis revealed 47 DMT-associated proteins, including 45 microtubule inner proteins (MIPs). We identified 10 sperm-specific MIPs, including seven classes of Tektin5 in the lumen of the A tubule and FAM166 family members that bind the intra-tubulin interfaces. Interestingly, the human sperm DMT lacks some MIPs compared with the mouse sperm DMT. We also discovered variants in 10 distinct MIPs associated with a subtype of asthenozoospermia characterized by impaired sperm motility without evident morphological abnormalities. Our study highlights the conservation and tissue/species specificity of DMTs and expands the genetic spectrum of male infertility.
Cell. 2023 Jun 06 [Epub ahead of print]
Lunni Zhou, Haobin Liu, Siyu Liu, Xiaoyu Yang, Yue Dong, Yun Pan, Zhuang Xiao, Beihong Zheng, Yan Sun, Pengyu Huang, Xixi Zhang, Jin Hu, Rui Sun, Shan Feng, Yi Zhu, Mingxi Liu, Miao Gui, Jianping Wu
Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou 310024, Zhejiang, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310024, Zhejiang, China; Institute of Biology, Westlake Institute for Advanced Study, Hangzhou 310024, Zhejiang, China., State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Histology and Embryology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, China., State Key Laboratory of Reproductive Medicine and Offspring Health, The Center for Clinical Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China., Center of Reproductive Medicine, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou 350001, China., Liangzhu Laboratory, Zhejiang University, Hangzhou 311121, Zhejiang, China., Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310024, Zhejiang, China; Institute of Biology, Westlake Institute for Advanced Study, Hangzhou 310024, Zhejiang, China., State Key Laboratory of Reproductive Medicine and Offspring Health, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Nanjing 211166, China. Electronic address: ., Liangzhu Laboratory, Zhejiang University, Hangzhou 311121, Zhejiang, China; Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, Zhejiang, China. Electronic address: ., Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou 310024, Zhejiang, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310024, Zhejiang, China; Institute of Biology, Westlake Institute for Advanced Study, Hangzhou 310024, Zhejiang, China. Electronic address: .