Differential expression and localization of CFTR and ENaC in mouse endometrium during pre‐implantation

Abstract

Interaction between the cystic fibrosis transmembrane conductance regulator (CFTR), a CAMP-activated Cl- channel, and epithelial Na+ channel (ENaC) has been proposed as the major mechanism regulating uterine fluid absorption and secretion. Differential expression of these ion channels may give rise to dynamic changes in the fluid environment affecting various reproductive events in the female reproductive tract. This study investigated the expression and localization of CFTR and ENaC during the pre-implantation period. Semi-quantitative reverse transcriptase polymerase chain reaction and immunohistochemistry were used to study the expression and localization of CFTR and ENaC in uteri collected from mature superovulated female mice. RT-PCR showed maximal ENaC and CFTR expression on day 3 after mating. Maximal immunoreactivity was also observed for both ENaC and CFTR on day 3 after mating. However, ENaC was immunolocalized to the apical membrane of both luminal and glandular epithelia, while CFTR was predominantly found in the stromal cells rather than the epithelial cells. Differential expression and localization of CFTR and ENaC provide a molecular mechanism by which maximal fluid absorption can be achieved immediately prior to implantation, to ensure the immobilization of the blastocyst necessary for implantation.

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

“…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.…”

“…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.…”

“…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).…”

ENaCs and ASICs as therapeutic targets

“…In the uterus, only ␣ENaC was detected, and expression varied with the estrus cycle and inversely to the expression of CFTR (74). Increased fluid absorption during periods when ENaC expression is increased may be required to facilitate blastocyst implantation (335,427). Postimplantation, uterine expression of ENaC gradually declines (74).…”

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

“…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.…”