Vol. 13, Issue 11, 3800-3810, November 2002

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

Karen P. Phillips,^* Mary Ann F. Petrunewich,^* Jennifer L. Collins,^* and Jay M. Baltz^*§¶

 ^*Hormones, Growth and Development Program, Ottawa Health Research Institute;  Departments of Obstetrics and Gynecology (Division of Reproductive Medicine), and  Cellular and Molecular Medicine, University of Ottawa; and  ^§Human IVF Laboratory, Ottawa Hospital, Ottawa, Ontario, K1Y 4E9 Canada

The HCO₃/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 HCO₃/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 HCO₃/Cl exchanger is not simply a general feature of metaphase, because activity did not decrease during first mitotic metaphase. Inactivation of the HCO₃/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 HCO₃/Cl exchanger. Inactivating MAPK in unfertilized MII eggs resulted in HCO₃/Cl exchanger activation. Preventing MAPK activation during first meiotic metaphase prevented the inactivation of HCO₃/Cl exchange. Conversely, activating MAPK in the GV oocyte resulted in inactivation of HCO₃/Cl exchange. These results imply that the HCO₃/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.