Expression and localization of epithelial sodium channel (ENaC) subunits in murine female reproductive tissues

The canonical epithelial sodium channel (ENaC) consists of three homologous subunits: α, β, and γ. While best known for mediating Na+ reabsorption within the distal nephron, ENaCs are expressed in other epithelia as well as nonepithelial tissues, including vascular endothelium, vascular smooth muscle, and antigen-presenting immune cells. Growing evidence suggests the involvement of ENaC in female fertility. However, the expression and regulation of ENaC subunits in female reproductive tissues remain elusive. We examined the expression of ENaC subunits in the murine female reproductive tract. Ovaries, oviducts, and uterine horns were harvested from adult female C57BL/6 mice for RNA isolation, tissue homogenate collection, and tissue fixation/sectioning. Quantitative PCR, immunoblotting, and immunofluorescence staining were performed to assess the expression and localization of ENaC subunits within these tissues. All three ENaC transcripts (Scnn1a, Scnn1b and Scnn1g) were detected in mouse ovaries, oviducts, and uterine horns. At protein level assessed by immunoblotting, the α subunit was detected in oviducts and uterine horns, but not in ovaries. In contrast, β and γ subunits were expressed in all three tissues with differences in abundance (ovary < oviduct < uterine horn). The expression of the β subunit and the active, cleaved forms of α and γ subunits in murine uteri are significantly higher in the pregnant females. We performed immunofluorescence localization of the γ subunit in these tissues, co-staining with markers of cilia, epithelial cells, and smooth muscle cells. γ subunit expression was detected in oviducts and uterine horns, but not ovaries. While present in the luminal epithelial folds of the distal region of the oviducts, the γ subunit was predominantly expressed in smooth muscle layers of the proximal regions. Within uterine horns, the γ subunit was highly expressed in smooth muscle cells of the myometrium but was largely absent in epithelial cells lining the lumen of the endometrium. Collectively, our work demonstrated the expression of ENaC subunits in different cell types within the female reproductive tract. The expression of ENaC within uteri appears dynamic and changes during pregnancy, suggesting a potential role of ENaC in mechanosensing and in fluid volume regulation in the female reproductive tract. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.