Differential Expression of Na⁺/H⁺-Exchanger (NHE-1, 2, and 4) Proteins and mRNA in Rodent’s Uterus under Sex Steroid Effect and at Different Phases of the Oestrous Cycle

Figure 7

The proposed mechanism underlying uterine fluid pH regulation in the endometrial epithelial cell under E influence and at Es. CAII, which is responsible for H⁺ and HCO₃⁻ generation, is upregulated by E and at Es. HCO₃⁻ is extruded into the lumen via the apically located SLC26A6 and CFTR, which have also been reported to be upregulated by E and at Es. In order to maintain intracellular pH homeostasis, H⁺ is expelled into the plasma via the basolaterally located NHE2 and NHE4 in-exchange with Na⁺, which is pumped back into the plasma via the basolaterally located Na⁺/K⁺-ATPase. The apically located NHE2 and NHE4 may be involved in luminal Na⁺ secretion in-exchange with H⁺, which further contributes to the alkalinization of the uterine luminal fluid via H⁺ removal. Upregulation of membrane bound CAXII under these conditions is responsible for the conversion of H⁺ to H2CO3. CAII: carbonic anhydrase II; CAXII: carbonic anhydrase XII; CFTR: Cystic Fibrosis Transmembrane Regulator, SLC26A6: Cl⁻/HCO₃⁻ exchanger, NHE: sodium-proton exchanger, Na⁺/K⁺-ATPase: Na⁺-K⁺-ATPase pump.