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Publication : Activation of the epithelial Na+ channel triggers prostaglandin E₂ release and production required for embryo implantation.

First Author  Ruan YC Year  2012
Journal  Nat Med Volume  18
Issue  7 Pages  1112-7
PubMed ID  22729284 Mgi Jnum  J:187642
Mgi Id  MGI:5437580 Doi  10.1038/nm.2771
Citation  Ruan YC, et al. (2012) Activation of the epithelial Na+ channel triggers prostaglandin E(2) release and production required for embryo implantation. Nat Med 18(7):1112-7
abstractText  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 Ca(2)(+) influx that leads to prostaglandin E(2) (PGE(2)) 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 PGE(2) production and release required for embryo implantation, defects that may be a cause of miscarriage and low success rates in IVF.
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