The effect of pharmacological perturbations of maturation promoting factor (MPF) and mitogen activated protein kinase (MAPK) in mouse eggs

Abstract

Inactivation of MAPK with the MEK1/2 inhibitor U0126 simultaneously parthenogenetically activates eggs, disrupts spindle-cortex docking and destabilizes spindle organization, yielding parthenogenotes that resemble mos-/- oocytes. Inactivation of MPF with the Cdk1 inhibitor roscovitine also parthenogenetically activates eggs, some of which resemble mos-/- oocytes, suggesting a reciprocal role for MPF in modulating MAPK activity. MAPK inactivation with U0126 was quick (1 h) and preceded the fall in MPF activity whereas MAPK inactivation after roscovitine treatment was similar to that of fertilization (5-7 h), suggesting the presence of a physiological inactivating mechanisms. A severe phenotype developed after U0126 and roscovitine co-treatment, characterized by incomplete cleavages and ball of actin that follows the drifting spindle. Development of the severe phenotype suggests MPF and MAPK inactivation have a synergistic effect on spindle dynamics and that the timing of inactivation is important for normal egg activation.