Institute of Pediatrics, Children's Hospital of Fudan University, State Key Laboratory of Genetic Engineering, Institutes of Biomedical Sciences, Shanghai Key Laboratory of Medical Epigenetics, Fudan University, Shanghai 200032, China.
Center for Reproductive Medicine and Fertility Preservation Program, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China.
Science. 2024 Aug 23;385(6711):eado1022. doi: 10.1126/science.ado1022.
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.
纺锤体双极化，即微管质量转化为双极纺锤体的过程，是染色体正确分离的前提。与有丝分裂细胞不同，人类卵母细胞纺锤体双极化的过程和机制尚不清楚。通过对 1800 多个人类卵母细胞进行高分辨率成像，我们揭示了在纺锤体双极化过程中形成的典型多极中间体状态，并阐明了该过程的机制。我们发现，在多个动粒簇中形成的小极有助于多极中间体的产生。我们进一步确定了 HAUS6、KIF11 和 KIF18A 在纺锤体双极化中的重要作用，并在以卵母细胞或胚胎缺陷为特征的不育患者中发现了这些基因的突变。这些结果为理解人类卵母细胞纺锤体双极化的生理和病理机制提供了线索。
