Cyclin B2 is required for progression through meiosis in mouse oocytes

Abstract

Cyclins associate with CDK1 to generate the M-phase-promoting factor (MPF) essential for progression through mitosis and meiosis. Previous studies concluded that CCNB2 is dispensable for cell cycle progression. Given our findings of high translation rates of CcnB2 mRNA in prophase-arrested oocytes, we have reevaluated its role during meiosis. CcnB2-/- oocytes undergo delayed germinal vesicle breakdown followed by a defective M-phase due to reduced pre-MPF activity. This disrupted maturation is associated with compromised CcnB1 and Mos mRNA translation and delayed spindle assembly. Given these defects, a significant population of oocytes fail to complete meiosis I because SAC remains activated and APC function is inhibited. In vivo, CCNB2 depletion leads to decreased oocyte developmental competence, compromised 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 rescues the meiotic phenotypes, demonstrating similar molecular properties but divergent modes of regulation of these cyclins.