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Mammalian oocytes are arrested at meiotic prophase I. The dual-specificity phosphatase CDC25B is essential for cyclin-dependent kinase 1 (CDK1) activation that drives resumption of meiosis. CDC25B reverses the inhibitory effect of the protein kinases WEE1/MYT1 on CDK1 activation. Cdc25b−/- female mice are infertile because oocytes cannot activate CDK1. To identify a role for CDC25B following resumption of meiosis, we restored CDK1 activation in Cdc25b−/- oocytes by inhibiting WEE1/MYT1, or expressing EGFP-CDC25A or constitutively active EGFP-CDK1 from microinjected cRNAs. Forced CDK1 activation in Cdc25b−/- oocytes allowed resumption of meiosis, but oocytes mostly arrested at metaphase I (MI) with intact spindles. Similarly, ∼1/3 of Cdc25b+/- oocytes with reduced amount of CDC25B arrest in MI. MI arrested Cdc25b−/- oocytes also display a transient decrease in CDK1 activity similar to Cdc25b+/+ oocytes during the MI-MII transition, whereas Cdc25b+/- oocytes exhibit only a partial APC/C activation and anaphase I entry. Thus, CDC25B is necessary for resumption of meiosis and the MI-MII transition.

After fertilization, remodeling of the oocyte and sperm genomes is essential to convert these highly differentiated non-dividing transcriptionally quiescent cells into early cleavage-stage transcriptionally active totipotent blastomeres. This developmental transition is accompanied by cell cycle adaptation such as lengthening or shortening of the gap phases G1 and G2. However, regulation of these cell cycle changes is poorly understood, especially in mammals. Checkpoint kinase 1 (CHK1) is a protein kinase that regulates cell cycle progression in somatic cells. Here, we show that CHK1 regulates cell cycle progression in early mouse embryos by restraining CDK1 kinase activity due to CDC25A phosphatase degradation. CHK1 kinase also ensures the long G2 phase needed for genome activation and reprogramming gene expression in 2-cell stage mouse embryos. Last,Chk1depletion leads to DNA damage and chromosome segregation errors that result in aneuploidy and infertility.