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Mechanisms of minor pole-mediated spindle bipolarization in human oocytes

Affiliations
  • 1Institute 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.
  • 2Center for Reproductive Medicine and Fertility Preservation Program, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China.
  • 3NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, Shanghai 200032, China.
  • 4Reproductive Hospital of Guangxi Zhuang Autonomous Region, Nanning 530029, China.
  • 5Hebei Clinical Research Center for Birth Defects, Department of Reproductive Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, China.
  • 6Laboratory for Reproductive Immunology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China.
  • 7Assisted Reproduction Center, Northwest Women’s and Children’s Hospital, Xi’an 710003, China.
  • 8Shanghai JIAI Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China.
  • 9Department of Assisted Reproduction, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200011, China.

Published on:

August 22, 2024

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.

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