ANALYSIS OF THE MECHANISM(S) OF METAPHASE-I ARREST IN MATURING MOUSE OOCYTES

Fully grown mouse oocytes are normally competent to progress from prop hase I to metaphase II without interruption. However, growing mouse oo cytes initially become only partially competent to undergo meiotic mat uration. Meiotic maturation in these oocytes does not progress beyond metaphase I. In contrast to the oocytes of most strains of mice, most oocytes of strain LT/Sv mice become arrested at metaphase I even when they are fully grown. The initiation of oocyte maturation is correlate d with an increase in p34(cdc2) kinase activity that continues to rise until metaphase I. The transition into anaphase I is normally correla ted with a decrease in p34(cdc2) kinase activity. This study demonstra ted that metaphase I arrest in both partially competent growing oocyte s and fully grown LT/Sv oocytes is correlated with a sustained elevati on of p34(cdc2) kinase activity. In fact, p34(cdc2) activity continued to increase during the time when activity normally decreased. In norm ally maturing oocytes, some, but not all, of the cyclin B, the regulat ory protein associated with p34(cdc2), became degraded in oocytes that entered anaphase I. In contrast, the amount of cyclin B present in th e metaphase I-arrested oocytes continued to increase at the time when it was being degraded in normal oocytes progressing to metaphase II. T hese results suggest that the progression of meiosis is arrested at me taphase I in both groups of oocytes because of continued p34(cdc2) kin ase activity sustained, at least in part, by restricted degradation of cyclin B. Finally, metaphase I arrest in these oocytes is sustained b y a mechanism that differs from that maintaining metaphase II arrest, since an inhibitor of protein phosphorylation, 6-DMAP, induced a drama tic decline in p34(cdc2) kinase activity and the resumption of meiosis in metaphase I-arrested oocytes but not in metaphase II-arrested oocy tes. Moreover, without 6-DMAP treatment, cyclin B was more stable in t he metaphase I-arrested oocytes than in metaphase II-arrested oocytes.