期刊
JOURNAL OF CELL SCIENCE
卷 135, 期 6, 页码 -出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.259807
关键词
Oocyte; Nuclear F-actin; Meiosis; Aneuploidy; Chromosome segregation; Infertility
类别
资金
- Wellcome Trust
- Royal Society [213470/Z/18/Z]
- Human Frontier Science Program Young Investigator Award [RGY0070/2019]
- University of Bristol
- Wellcome Trust [213470/Z/18/Z] Funding Source: Wellcome Trust
Formation of healthy mammalian eggs requires specialised F-actin structures, which decline with female reproductive ageing. Manipulating the transfer of actin monomers in the nucleus affects oocyte development. This study provides insights into the cellular structural defects associated with female infertility.
Formation of healthy mammalian eggs from oocytes requires specialised F-actin structures. F-actin disruption produces aneuploid eggs, which are a leading cause of human embryo deaths, genetic disorders and infertility. We found that oocytes contain prominent nuclear F-actin structures that are correlated with meiotic developmental capacity. We demonstrate that nuclear F-actin is a conserved feature of healthy mammalian oocytes and declines significantly with female reproductive ageing. Actin monomers used for nuclear F-actin assembly are sourced from an excess pool in the oocyte cytoplasm. Increasing monomeric G-actin transfer from the cytoplasm to the nucleus or directly enriching the nucleus with monomers led to assembly of stable nuclear F-actin bundles that significantly restrict chromatin mobility. By contrast, reducing G-actin monomer transfer by blocking nuclear import triggered assembly of a dense cytoplasmic F-actin network that is incompatible with healthy oocyte development. Overall, our data suggest that the large oocyte nucleus helps to maintain cytoplasmic F-actin organisation and that defects in this function are linked with reproductive age-related female infertility. This article has an associated First Person interview with Federica Giannini, joint first author of the paper.
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