Distribution and Regulation of ENaC Subunit and CFTR mRNA Expression in Murine Female Reproductive Tract

Abstract

The present study investigated the regional distribution and cyclic changes in the mRNA expression of epithelial Na+ channel (ENaC) subunit and cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated Cl- channel, in adult female mouse reproductive tract. In situ hybridization revealed that in contrast to the abundant expression of CFTR, ENaC (alpha, beta, gamma) mRNA signal was not detected throughout the estrus cycle in the ovary and oviduct. Messenger RNA for all ENaC subunits was abundantly detected in the cervical and vaginal epithelia throughout the estrus cycle but for CFTR, mRNA was found only at proestrus. In the uterine epithelium, alphaENaC mRNA was detected at diestrus but not found at any other stage, while CFTR mRNA was only detected at early estrus but not other stages. Semi-quantitative RT-PCR detected mRNA for all ENaC subunits in the uterus throughout the cycle with maximal expression at diestrus and CFTR mRNA was only found in the early stages of the cycle. The involvement of ENaC and CFTR in Na+ absorption and Cl- secretion was demonstrated in cultured endometrial epithelia using the short-circuit current technique and found to be influenced by ovarian hormones. Taken together, these data indicate a main secretory role of the ovary and oviduct and a predominantly absorptive role of the cervix and vagina. The present results also suggest an ability of the uterus to secrete and absorb at different stages of the estrus cycle. Variations in the fluid profiles may be dictated by the regional and cyclic variations in expression of ENaC and CFTR and are likely to contribute to various reproductive events in different regions of the female reproductive tract.

Regulation of miR-101/miR-199a-3p by the epithelial sodium channel during embryo implantation: involvement of CREB phosphorylation

“…Together with the demonstrated capacity of ENaC in the regulation of miRNAs, these suggest that ENaC might mediate other types of signals in regulation of miRNAs in different physiological contexts. For example, while 17b-estradiol (E 2 ) is known to downregulate uterine ENaC in mice (Chan et al 2002), it has also been reported to promote miR-199a expression in rat uterus (Xia et al 2014). The promoting effect of E 2 on the miRNA might be mediated through its downregulating effect on ENaC, given the present results showing the upregulation of miR-199a in response to inhibition or knockdown of ENaC.…”

“…Taken together, these results suggest that miR-101 and miR-199a-3p are involved in the modulation of the expression of COX2 in response to ENaC activation during implantation. Interestingly, ENaC is also known to be activated by mechano-stimuli (Fronius & Clauss 2008) and its expression in the endometrium is subject to alteration in ovarian hormones (Chan et al 2002, Yang et al 2004. Together with the demonstrated capacity of ENaC in the regulation of miRNAs, these suggest that ENaC might mediate other types of signals in regulation of miRNAs in different physiological contexts.…”

“…The amiloride-sensitive epithelial sodium channel (ENaC) is expressed in various epithelia, including endometrial epithelium (Chan et al 2002, Yang et al 2004, Ruan et al 2014, which is essential to sodium and water homeostasis in the body (Hummler et al 1996, Salker 2010. ENaC has been shown to exhibit cyclic expression pattern during the estrous cycle with a high expression level observed at diestrus and peri-implantation period (Chan et al 2002, Yang et al 2004).…”

“…ENaC has been shown to exhibit cyclic expression pattern during the estrous cycle with a high expression level observed at diestrus and peri-implantation period (Chan et al 2002, Yang et al 2004). Like its well-known role in other epithelia, ENaC has been demonstrated to be involved in uterine fluid absorption, which is suggested to be responsible for the reduced uterine fluid volume during embryo implantation (Chan et al 2000a,b, 2001, Ruan et al 2014.…”

Gene expression profiling of bovine endometrium during the oestrous cycle: detection of molecular pathways involved in functional changes

“…At dioestrus, a number of transcripts for different enzymes and for proteins involved in transport processes are upregulated. The cyclic regulation of uterine fluids in the endometrium by differential expression of genes coding for ion channels was first shown by Chan et al (2002). The identification of three mRNAs coding for ion channels (group 'transport') provides further evidence for this.…”