The mechanism of acentrosomal spindle assembly in human oocytes

Author:

Wu Tianyu1ORCID,Dong Jie1ORCID,Fu Jing2ORCID,Kuang Yanping3ORCID,Chen Biaobang4ORCID,Gu Hao1ORCID,Luo Yuxi1ORCID,Gu Ruihuan2ORCID,Zhang Meiling5ORCID,Li Wen5ORCID,Dong Xi6ORCID,Sun Xiaoxi2ORCID,Sang Qing1ORCID,Wang Lei1ORCID

Affiliation:

1. 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.

2. Shanghai Ji Ai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China.

3. Department of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.

4. NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, Shanghai 200032, China.

5. 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.

6. Reproductive Medicine Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China.

Abstract

Meiotic spindle assembly ensures proper chromosome segregation in oocytes. However, the mechanisms behind spindle assembly in human oocytes remain largely unknown. We used three-dimensional high-resolution imaging of more than 2000 human oocytes to identify a structure that we named the human oocyte microtubule organizing center (huoMTOC). The proteins TACC3, CCP110, CKAP5, and DISC1 were found to be essential components of the huoMTOC. The huoMTOC arises beneath the oocyte cortex and migrates adjacent to the nuclear envelope before nuclear envelope breakdown (NEBD). After NEBD, the huoMTOC fragments and relocates on the kinetochores to initiate microtubule nucleation and spindle assembly. Disrupting the huoMTOC led to spindle assembly defects and oocyte maturation arrest. These results reveal a physiological mechanism of huoMTOC-regulated spindle assembly in human oocytes.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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