Bicarbonate/chloride exchange and intracellular pH throughout preimplantation mouse embryo development

HCO3-/Cl- exchanger activity, which regulates intracellular pH (pHi) in the alkaline range, has been shown to be present throughout preimplantation mouse embryo development and to be necessary for embryo viability. We have characterized HCO3-/Cl- exchange activity and its regulation of pHi throughout preimplantation development (1-cell, 2-cell, morula, and blastocyst stages). Embryos at each stage can recover from alkalosis. Recovery was dependent on external [Cl-], activated by increased pHi, and inhibited by the anion transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and external HCO3-. Dependence of exchanger activity on external [Cl-] and pHi remained unchanged during preimplantation development. However, the concentration at which DIDS inhibits the maximal response by 50% increased significantly (by approximately 5-fold) after the one-cell stage. In addition, HCO3-/Cl- exchange activity decreased over the course of development, with significantly lower activity at the morula and blastocyst stages relative to the one- and two-cell stages, coinciding with the movement of embryo from the high pH environment of the oviduct to the lower pH environment of the uterus.