Activation of the epithelial Na+ channel triggers prostaglandin E₂ release and production required for embryo implantation.
Embryo implantation remains a poorly understood process. We demonstrate here that activation of the epithelial Na⁺ channel (ENaC) in mouse endometrial epithelial cells by an embryo-released serine protease, trypsin, triggers Ca²⁺ influx that leads to prostaglandin E₂ (PGE₂) release, phosphorylation of the transcription factor CREB and upregulation of cyclooxygenase 2, the enzyme required for prostaglandin production and implantation. We detected maximum ENaC activation, as indicated by ENaC cleavage, at the time of implantation in mice. Blocking or knocking down uterine ENaC in mice resulted in implantation failure. Furthermore, we found that uterine ENaC expression before in vitro fertilization (IVF) treatment is markedly lower in women with implantation failure as compared to those with successful pregnancy. These results indicate a previously undefined role of ENaC in regulating the PGE₂ production and release required for embryo implantation, defects that may be a cause of miscarriage and low success rates in IVF.
Epithelial Cell Biology Research Centre, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.
Ye Chun
YC
Ruan
Jing Hui
JH
Guo
Xinmei
X
Liu
Runju
R
Zhang
Lai Ling
LL
Tsang
Jian Da
JD
Dong
Hui
H
Chen
Mei Kuen
MK
Yu
Xiaohua
X
Jiang
Xiao Hu
XH
Zhang
Kin Lam
KL
Fok
Yiu Wa
YW
Chung
Hefeng
H
Huang
Wen Liang
WL
Zhou
Hsiao Chang
HC
Chan
D000818:Animals; D015153:Blotting, Western; D018920:Coculture Techniques; D003656:Decidua / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D010064:Embryo Implantation; D004717:Endometrium / Q000166:cytology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans; D015640:Ion Channel Gating; D051379:Mice; D008954:Models, Biological; D018408:Patch-Clamp Techniques; D015398:Signal Transduction; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism
D053503:Epithelial Sodium Channels; D015232:Dinoprostone