Figure 6. SLC26A3 and SLC26A6 work in concert with CFTR in regulating HCO₃⁻ transport in preimplantation embryo.

Working model for the regulation of early embryo cleavage by SLC26A3 and SLC26A6 in CFTR/HCO₃⁻-dependent activation of miR-125b. The HCO₃⁻ influx is mediated by SLC26A3 and SLC26A6 with an exchange of 2Cl⁻/ HCO₃⁻. Apart from its reported role in conducting HCO₃⁻ directly, CFTR act as a Cl⁻ channel to provide a recycling pathway for Cl⁻ that is required for SLC26A3 and SLC26A6 function. The sites of action for inhibitors CFTRinh172, niflumate, and DIDS, as well as the intracellular HCO₃⁻-dependent events, are also shown. HCO₃⁻ influx mediated by the cooperative action of SLC26A3, SLC26A6 and CFTR activates soluble adenylyl cyclase (sAC) which increase the level of cAMP. This in turn activates PKA/NFkB signaling cascade which increases the expression of miR125b. Expression of miR125b is required for embryo cleavage through suppressing the expression of p53 and p21. Vm, membrane potential; [pH]i, intracellular pH.