In mitosis, cyclin A2 is destroyed in prometaphase and is necessary for stable progression through mitosis. However, in female meiosis cyclin A2 persists during metaphase of meiosis II where it regulates microtubule stability, allows normal MII spindle formation, and prevents merotelic attachments and lagging chromosomes on MII exit. There remains little known about the role and regulation of cyclin A2 during the transition from meiosis to mitosis in mammals. We developed a conditional knockout mouse model by crossing cyclin A2 floxed mice with Zp3 Cre mice, and investigated the functions of cyclin A2 in the transition from egg to embryo. Our studies with cyclin A2-/-oocytes showed delays and abnormalities in proncleus formation, changes in activity of Cdk1 and levels of p-Plk1. After parthenogenetic activation there was an increase in abnormalities during early development and a reduced rate of progression to the blastocyst stage. These abnormalities underlie an overall reduction in fecundity of cyclin A2-/- mice. These results demonstrate a role of cyclin A2 in the oocyte-embryo transition.