LAUSR

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 leads to assembly of stable nuclear F-actin bundles that significantly restrict chromatin mobility. Conversely, reducing G-actin monomer transfer by blocking nuclear import triggers assembly of a dense cytoplasmic F-actin network that is incompatible with healthy oocyte development. Our data overall suggest that the large oocyte nucleus helps to maintain cytoplasmic F-actin organisation and that defects in this function could be linked with reproductive age-related female infertility.