Evidence that protein kinase C (PKC) participates in the meiosis I to meiosis II transition in mouse oocytes

Oocytes from LTXBO mice exhibit a delayed entry into anaphase I and frequen tly enter interphase after the first meiotic division. This unique oocyte m odel was used to test the hypothesis that protein kinase C (PKC) may regula te the meiosis I-to-meiosis II transition. PKC activity was detected in LTX BO oocytes at prophase I and increased with meiotic maturation, with the hi ghest (P < 0.05) activity observed at late metaphase I(MI). Treatment of la te MI-stage oocytes with the PKC inhibitor, bisindolylmaleimide I(BIM), tra nsiently reduced (P < 0.05) M-phase-promoting factor (MPF) activity and pro moted (P < 0.05) progression to metaphase II (MII), while mitogen-activated protein kinase (MAPK) activity remained elevated during the MI-to-MII tran sition. Confocal microscopy analysis of LTXBO oocytes during this transitio n showed PKC-delta associated with the meiotic spindle and then with the ch romosomes at MII. Inhibition of PKC activity also prevented untimely entry into interphase, but only when PKC activity was reduced in oocytes before t he progression to MII and thus indicates that the transition into interphas e is directly associated with the delayed triggering of anaphase I. Moreove r, the defect(s) that initiate activation occur upstream of MAPK, as suppre ssion of PKC activity failed to prevent activation by Mos(tm1Ev)/Mos(tm1Ev) LTXBO oocytes expressing no detectable MAPK activity. In summary, PKC part icipates in the regulatory mechanisms that delay entry into anaphase I in L TXBO oocytes, and the disruption promotes untimely entry into interphase. T hus, loss of regulatory control over PKC activity during oocyte maturation disrupts the critical MI-to-Mn transition, leading to a precocious exit fro m meiosis. (C) 2001 Academic Press.