Mechanisms of minor pole–mediated spindle bipolarization in human oocytes
Tianyu Wu, Yuxi Luo, Meiling Zhang, Biaobang Chen, Xingzhu Du, Hao Gu, Siyuan Xie, Zhiqi Pan, Ran Yu, Ruiqi Hai, Xiangli Niu, Guimin Hao, Liping Jin, Juanzi Shi, Xiaoxi Sun, Yanping Kuang, Wen Li, Qing Sang, Lei Wang
Abstract
Spindle bipolarization, the process of a microtubule mass transforming into a bipolar spindle, is a prerequisite for accurate chromosome segregation. In contrast to mitotic cells, the process and mechanism of spindle bipolarization in human oocytes remains unclear. Using high-resolution imaging in more than 1800 human oocytes, we revealed a typical state of multipolar intermediates that form during spindle bipolarization and elucidated the mechanism underlying this process. We found that the minor poles formed in multiple kinetochore clusters contribute to the generation of multipolar intermediates. We further determined the essential roles of HAUS6, KIF11, and KIF18A in spindle bipolarization and identified mutations in these genes in infertile patients characterized by oocyte or embryo defects. These results provide insights into the physiological and pathological mechanisms of spindle bipolarization in human oocytes.