Involvement of MEK-mitogen-activated protein kinase pathway in follicle-stimulating hormone-induced but not spontaneous meiotic resumption of mouse oocytes

Mitogen-activated protein (MAP) kinase has been reported to be activated du ring oocyte meiotic maturation in a variety of mammalian species. However, the mechanism(s) responsible for MAP kinase activation and the consequence of its premature activation during gonadotropin-induced oocyte meiotic resu mption have not been examined. The present experiments were conducted to in vestigate the possible role of MAP kinase in FSH-induced and spontaneous oo cyte meiotic resumption in the mouse. MAP kinase kinase (MAPKK, MEK) inhibi tor, PD98059 or U0126, produced a dose-dependent inhibitory effect on both FSH-induced oocyte meiotic resumption and MAP kinase activation in the oocy tes. However, the same inhibitor did not block spontaneous meiotic resumpti on of either denuded or cumulus cell-enclosed mouse oocytes, despite the ac tivity of MAP kinase being totally inhibited. Immunoblotting the oocytes an d the cumulus cells with the anti-active MAP kinase antibody showed that MA P kinase activity in the oocytes was detected at 8 h of FSH treatment, prio r to germinal vesicle breakdown and increased as maturation progressed in t he following culture period. In the cumulus cells, MAP kinase was activated even faster, its activity was detected at I h of FSH stimulation and incre ased gradually until 8 h of FSH treatment, then decreased and diminished af ter 12 h of FSH action. These data demonstrated that the MEK-MAP kinase pat hway is implicated in FSH-induced but not spontaneous oocyte meiotic resump tion.