Involvement of Cl?/HCO3- exchanger SLC26A3 and SLC26A6 in preimplantation embryo cleavage

Abstract

Bicarbonate (HCO3?) is essential for preimplantation embryo development. However, the mechanism underlying the HCO3? transport into the embryo remains elusive. In the present study, we examined the possible involvement of Cl?/HCO3? exchanger in mediating HCO3? transport into the embryo. Our results showed that depletion of extracellular Cl?, even in the presence of HCO3?, suppressed embryo cleavage in a concentration-dependent manner. Cleavage-Associated HCO3?-dependent events, including increase of intracellular pH, upregulation of miR-125b and downregulation of p53, also required Cl?. We further showed that Cl?/HCO3? 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 HCO3?-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 HCO3? 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.