Characterization of AURKA knockout in mouse oocytes

Aneuploidy accounts for nearly 30% of all miscarriages and most of these aneuploidies are due to maternal errors during Meiosis I (MI). Cell division in both mitotic and meiotic cells requires proteins that ensure correct chromosome segregation into the resulting daughter cells. In contrast to mitotic cells that have two aurora kinase orthologs, AURKA and AURKB, to help prevent incorrect chromosome segregation, meiosis has an additional AURK, AURKC. In mouse oocytes, AURKA can fully support meiotic maturation by itself in the absence of AURKB/C (Nguyen et al. 2018). To further investigate the essential role of AURKA in oocytes, we analyzed oocyte-specific AURKA knockout (A KO) mice. Surprisingly, we found that A KO female mice are sterile, however, they do ovulate. Furthermore, we demonstrate that, in the absence of AURKA, oocytes cannot form elongated bipolar spindles, complete meiosis I, or extrude a polar body, resulting in oocytes that have arrested at metaphase I (Met I) prior to ovulation. We also determined that this Met I arrest is independent of the spindle assembly checkpoint. Results of these experiments further demonstrate that AURKA is essential for oocyte meiotic maturation and is required for correct spindle formation and chromosome segregation.M.S.Includes bibliographical reference