Cyclin B2 is required for progression through meiosis in mouse oocytes

Abstract

Cyclins associate with CDK1 to generate the M-phase-promoting factor (MPF) activity essential for progression through mitosis and meiosis. Although CCNB1 is required for embryo development, previous studies concluded that CCNB2 is dispensable for cell cycle progression. Given our findings of high CcnB2 mRNA translation rates in prophase-arrested oocytes, we have reevaluated the role of this cyclin during meiosis. CcnB2−/- oocytes undergo delayed germinal vesicle breakdown and show defects during metaphase to anaphase transition. This defective maturation is associated with compromised CcnB1 and Mos mRNA translation, delayed spindle assembly, and increased errors in chromosome segregation. Given these defects, a significant percentage of oocytes fail to complete meiosis I because the SAC remains active and APC function is inhibited. In vivo, CCNB2 depletion cause ovulation of immature oocytes, compromised female fecundity, and premature ovarian failure. These findings demonstrate that CCNB2 is required to assemble sufficient pre-MPF for timely meiosis reentry and progression. Although endogenous cyclins cannot compensate, overexpression of CCNB1/2 rescues the meiotic phenotypes, indicating similar molecular properties but divergent modes of regulation of these cyclins.