Activation of the epithelial Na+channel triggers prostaglandin E2release and production required for embryo implantation

Yechun Ruan, Jing Hui Guo, Xinmei Liu, Runju Zhang, Lai Ling Tsang, Jian Da Dong, Hui Chen, Mei Kuen Yu, Xiaohua Jiang, Xiao Hu Zhang, Kin Lam Fok, Yiu Wa Chung, Hefeng Huang, Wen Liang Zhou, Hsiao Chang Chan

Research output: Journal article publicationJournal articleAcademic researchpeer-review

103 Citations (Scopus)

Abstract

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 cyclooxygenasE2, 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 PGE2production and release required for embryo implantation, defects that may be a cause of miscarriage and low success rates in IVF.
Original languageEnglish
Pages (from-to)1112-1117
Number of pages6
JournalNature Medicine
Volume18
Issue number7
DOIs
Publication statusPublished - 1 Jul 2012
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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