INTRODUCTION One of the striking peculiarities of meiotic maturation in mouse oocytes concerns the first meiotic M phase (MI). In contrast to all other M phases in vertebrate cells (except the metaphase II arrest), the first meiotic M phase is long, usually lasting between 7 and 10 hours. However, the precise timing of MI seems to be genetically controlled, as shown by significant variations in the speed of meiotic maturation between different strains of mice, in particular the strains CBA/Kw and KE (Polanski, 1986, 1997). CBA/Kw oocytes extrude the first polar body about 7 hours after germinal vesicle breakdown (GVBD), whilst the KE oocytes do so approximately 3-4 hours later, that is 10-11 hours after GVBD. The major cell cycle kinase, the cyclin/p34 cdc2 kinase (maturation promoting factor; MPF) is activated just before GVBD and its activity rises progressively until it reaches a plateau at MI (Choi et al., 1991; Verlhac et al., 1994). By this time, the microtubules have formed into a spindle, but exit from the first meiotic M phase is delayed for a further 3-4 hours. Mitotic cyclins are the regulatory subunits of the p34 cdc2 kinase that are synthesized throughout the cell cycle and destroyed at each cell division (Evans et al., 1983). Cyclin degradation is a proteolytic event involving the ubiquitin pathway that is regulated throughout the cell cycle, such that the cyclins remain stable in interphase and are destroyed during a short interlude just before the metaphase-anaphase transition (for a review, see Townsley and Ruderman, 1998). It was reported that the synthesis of cyclin B1 increases gradually during meiosis I in mouse oocytes (when MPF activity rises) and the newly synthesized protein becomes complexed immediately with the p34 cdc2 kinase (Hampl and Eppig, 1995b; Winston, 1997). Thus, these data suggest that MPF activity is regulated by a translation-dependent mechanism that determines the level of cyclin synthesis. Similar increases in cyclin B synthesis have also been observed during the transition from G 2 to metaphase I in oocytes from Patella and Xenopus (Gautier and Maller, 1991; Kobayashi et al., 1991; van Loon et al., 1991; Galas et al., 1993). In this work, we have studied the role of cyclin B1 metabolism in the timing of meiotic maturation using oocytes from the KE and CBA/Kw mouse strains. 4989 Development 125, 4989-4997 (1998) Printed in Great Britain © The Company of Biologists Limited 1998 DEV4079 To study the mechanisms involved in the progression of meiotic maturation in the mouse, we used oocytes from two strains of mice, CBA/Kw and KE, which differ greatly in the rate at which they undergo meiotic maturation. CBA/Kw oocytes extrude the first polar body about 7 hours after breakdown of the germinal vesicle (GVBD), whilst the oocytes from KE mice take approximately 3-4 hours longer. In both strains, the kinetics of spindle formation are comparable. While the kinetics of MAP kinase activity are very similar in both strains (although slightly faster in CBA/Kw), the rise of cdc2 kinase activity is very rapid in CBA/Kw oocytes and slow and diphasic in KE oocytes. When protein synthesis is inhibited, the activity of the cdc2 kinase starts to rise but arrests shortly after GVBD with a slightly higher level in CBA/Kw oocytes, which may correspond to the presence of a larger pool of cyclin B1 in prophase CBA/Kw oocytes. After GVBD, the rate of cyclin B1 synthesis is higher in CBA/Kw than in KE oocytes, whilst the overall level of protein synthesis and the amount of messenger RNA coding for cyclin B1 are identical in oocytes from both strains. The injection of cyclin B1 messenger RNA in KE oocytes increased the H1 kinase activity and sped up first polar body extrusion. Finally, analysis of the rate of maturation in hybrids obtained after fusion of nuclear and cytoplasmic fragments of oocytes from both strains suggests that both the germinal vesicle and the cytoplasm contain factor(s) influencing the length of the first meiotic M phase. These results demonstrate that the rate of cyclin B1 synthesis controls the length of the first meiotic M phase and that a nuclear factor able to speed up cyclin B synthesis is present in CBA/Kw oocytes. Key words: Cyclin, H1 kinase, MAP kinase, Meiosis, Mouse oocyte SUMMARY Cyclin synthesis controls the progression of meiotic maturation in mouse oocytes Zbigniew Polanski 1,2 , Emilie Ledan 1 , Stéphane Brunet 1 , Sophie Louvet 1 , Marie-Hélène Verlhac 1 , Jacek Z. Kubiak 1 and Bernard Maro 1, * 1 Laboratoire de Biologie Cellulaire du Développement, Institut Jacques Monod, CNRS, Université Paris 6 and Université Paris 7, 2 place Jussieu, F-75005 Paris, France 2 Institute of Zoology, Jagiellonian University, Ingardena 6, 30-060 Krakow, Poland *Author for correspondence (e-mail: maro@ijm.jussieu.fr) Accepted 7 October; published on WWW 12 November 1998