The intracellular pH-regulatory HCO3-/Cl- exchanger in the mouse oocyte is inactivated during first meiotic metaphase and reactivated after egg activation via the MAP kinase pathway.

The HCO(3)(-)/Cl(-) exchanger is quiescent in the unfertilized mouse egg but is highly active in regulating intracellular pH in the early embryo and required for normal development. We show here that the HCO(3)(-)/Cl(-) exchanger is active in first meiotic prophase (GV) oocyte but inactivated during meiotic metaphase before the MI to MII transition. Reactivation does not occur until the activated egg enters interphase. A quiescent HCO(3)(-)/Cl(-) exchanger is not simply a general feature of metaphase, because activity did not decrease during first mitotic metaphase. Inactivation of the HCO(3)(-)/Cl(-) exchanger during MI coincided with the activation of MAP kinase (MAPK), whereas its reactivation coincided with the loss of MAPK activity after egg activation. Maintaining high MAPK activity after egg activation prevented the normal reactivation of the HCO(3)(-)/Cl(-) exchanger. Inactivating MAPK in unfertilized MII eggs resulted in HCO(3)(-)/Cl(-) exchanger activation. Preventing MAPK activation during first meiotic metaphase prevented the inactivation of HCO(3)(-)/Cl(-) exchange. Conversely, activating MAPK in the GV oocyte resulted in inactivation of HCO(3)(-)/Cl(-) exchange. These results imply that the HCO(3)(-)/Cl(-) exchanger in mouse oocytes is negatively regulated by MAPK. Thus, suppression of pH-regulatory mechanisms during meiosis is a novel function of MAPK and cytostatic factor activity in the oocyte.