331. INVESTIGATING THE ROLE OF CYCLIN A2 DURING OOCYTE MEIOSIS

Abstract

Aneuploidy is often derived from chromosomal segregation errors in oocytes, leading to Down Syndrome and early embryo loss. Thus it is important to understand the molecular control of female meiosis. Cyclins and cyclin-dependent kinases (CDKs), particular those contributing to Maturation Promoting Factor (MPF, or CDK1) activity, play key roles in regulating meiosis. While cyclin B1 is classically regarded as the regulatory component of MPF, cyclin A2 can also bind and activate CDK1, and in mammalian somatic cells it is known to promote both G1/S and G2/M transitions. There is an absolute requirement for cyclin A2 during development and differentiation as its deficiency results in early embryonic lethality. As such, cyclin A2 has not been extensively studied, particularly as to its role in meiosis. To examine the role cyclin A2 plays during mammalian female meiosis, we carried out knockdown experiments. Microinjection into mouse oocytes of cyclin A2 siRNA induced a ~70% knockdown. Cyclin A2 knockdown did not inhibit germinal vesicle breakdown but did act to delay it. Extrusion of the first polar body was significantly reduced (P = 0.002) in comparison to non-injected controls and those injected with a negative control siRNA. Furthermore, microinjection of cyclin A2 can stimulate entry into meiosis. Thus it seems possible that cyclin A2/CDK can exhibit MPF activity. In conclusion, our data suggest that cyclin A2 can regulate meiotic entry in oocytes and also plays an important role in successful passage through the first meiotic division.