Altered cyclic expression of epithelial Na⁺ channel subunits and cystic fibrosis transmembrane conductance regulator in mouse endometrium by a low sodium diet

Abstract

Epithelial Na+ channel (ENaC) and cystic fibrosis transmembrane conductance (CFTR) have been shown to exhibit cyclic expression patterns in the uterus and demonstrated to play important roles in regulating uterine fluid absorption and secretion. The present study investigated the effect of a low Na+ diet on the cyclic expression of uterine ENaC subunits and CFTR in mice. Ten to 12 weeks old ICR mice with synchronized estrus cycle were fed with a low sodium diet for at least 2 weeks and the mRNA level of these ion channels was examined by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). Functional channel activities in primary cultures of endometrial epithelia were assessed by the short-circuit current (Isc) technique. The characteristic cyclic expression of ENaC subunits throughout the estrus cycle remained unchanged but their expression levels towards the diestrus stage were drastically elevated. The cyclic expression pattern of CFTR was disrupted with suppressed expression throughout the cycle. Isc measurements showed that treatment of cultured endometrial epithelial cells with aldosterone, the major hormone expected to be elevated during the low sodium diet, resulted in prominent increase in ENaC channel activity. The altered cyclic expression of uterine ENaC and CFTR by a low sodium diet suggests that these ion channels may be affected by elevated circulating aldosterone, which may disrupt reproductive events in the uterus.

LEFTYA Activates the Epithelial Na+ Channel (ENaC) in Endometrial Cells via Serum and Glucocorticoid Inducible Kinase SGK1

“…Failure to down-regulate LEFTYA secretion during the mid-luteal phase of the cycle may lead to premature 'closure' of the uterine lumen via ENaC-mediated fluid absorption, resulting in implantation failure [20,39]. The present observations, however, do not provide insight into the purported inhibitory effects of LEFTYA on decidualization of the endometrial stroma [40,41].…”

“…Recently, ion channels in the endometrium have emerged as important players in regulating endometrial receptivity. Abnormal expression or function of ion channels in the endometrium may lead to impaired endometrial receptivity and implantation failure [20,21]. ENaC is localized at the apical membrane in a wide variety of epithelia, including endometrial epithelium.…”

Morphologic effects of epithelial ion channels on the mouse uterus: differences between raloxifene analog (LY117018) and estradiol treatments

“…9 However, the expressions of ENaC and CFTR change with estrus cycle in mouse uterine endothelium, even under aldosterone stimulating circumstances. 19 In this study we demonstrated the induction of CFTR and repression of ENaC in E2-treated -22mouse uterus. These findings suggest that E2 is an important regulator of these ion channel genes in uterus.…”

Differential regulation of cystic fibrosis transmembrane conductance regulator and Na+,K+-ATPase in gills of striped bass, Morone saxatilis: effect of salinity and hormones

“…In FW Atlantic salmon, CFTR-I mRNA levels were unaffected by 5-day cortisol implants; however, when fish subsequently were sham transferred to FW, CFTR-I transcript levels increased after 24 h (Singer et al 2003). Interestingly, in mouse endometrium, hyperaldosteronaemia induced by a low-sodium diet depresses CFTR and increases ENaC channel expression (Tsang et al 2004).…”