FIGURE 1.

Schematic model depicting the mechanisms of meiotic arrest. Meiotic arrest in fully grown oocytes is required by the synthesis and maintenance of high levels of cAMP, the arrest state is maintained by the cooperation of granulosa cells and oocytes in the follicles. In mural granulosa cells, FSH binds its receptor (FSHR), collaborating with androgen/AR, estrogen/ER, and the TGF-β/TGFBR2 signal pathway to promote NPPC transcription and increase NPPC production. In cumulus granulosa cells, FSH binds FSHR, collaborating with androgen/AR and estrogen/ER to promote NPR2 transcription and increase NPR2 production. NPPC actives NPR2, GTP is converted into cGMP, then cGMP enters the oocyte through CX37 gap junctions. In oocytes, cGMP inhibits PDE3A activity, prevents the degradation of cAMP, cAMP activates protein kinase A (PKA) that in turn activates the WEE1B kinase and inhibits the CDC25B phosphatase leading to the inactivation of CDK1. In addition, CDC25B protein level is inhibited by histone lysine demethylases 1A (KDM1A). The constant degradation of cyclin B1/2 (cycB1/2) by APC/CDH1 prevents MPF activation in the arrested oocytes.