Involvement of Cl(−)/HCO(3)(−) exchanger SLC26A3 and SLC26A6 in preimplantation embryo cleavage

Bicarbonate (HCO(3)(−)) is essential for preimplantation embryo development. However, the mechanism underlying the HCO(3)(−) transport into the embryo remains elusive. In the present study, we examined the possible involvement of Cl(−)/HCO(3)(−) exchanger in mediating HCO(3)(−) transport into the embryo. Our results showed that depletion of extracellular Cl(−), even in the presence of HCO(3)(−), suppressed embryo cleavage in a concentration-dependent manner. Cleavage-associated HCO(3)(−)-dependent events, including increase of intracellular pH, upregulation of miR-125b and downregulation of p53, also required Cl(−). We further showed that Cl(−)/HCO(3)(−) exchanger solute carrier family 26 (SLC26) A3 and A6 were expressed at 2-cell through blastocyst stage. Blocking individual exchanger’s activity by inhibitors or gene knockdown differentially decreased embryo cleavage and inhibited HCO(3)(−)-dependent events, while inhibiting/knocking down both produced an additive effect to an extent similar to that observed when CFTR was inhibited. These results indicate the involvement of SLC26A3 and A6 in transporting HCO(3)(−) essential for embryo cleavage, possibly working in concert with CFTR through a Cl(−) recycling pathway. The present study sheds light into our understanding of molecular mechanisms regulating embryo cleavage by the female reproductive tract.