ArticleNature medicine2012
Activation of the epithelial Na+ channel triggers prostaglandin E₂ release and production required for embryo implantation.
Article in Nature medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04865367 (To Investigate How Secreted-embryo-derived Trypsin Initiates, Maintains and Terminates Ca2+), which is not on this map. Cited by 85 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
To Investigate How Secreted-embryo-derived Trypsin Initiates, Maintains and Terminates Ca2+ (Intracellular Calcium) Signals in Uterine Epithelial Cells
Who cites it
85 citing papers in PubMed, 1 synthesis or guideline pooled it, 164 citations in OpenAlex.
- Intralipid therapy and adverse reproductive outcome: is there any evidence?Reproduction & fertility · 2021Pooled it
- IGFBP5 Restores Endometrial Receptivity and Rescues Implantation Failure in Polycystic Ovary Syndrome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Non-coding RNAs in congenital heart disease and placental development: Bridging molecular mechanisms to clinical biomarkers and therapies.Non-coding RNA research · 2026Review
- Advances and challenges of endometrial organoids in modeling endometrial function: basic, clinical, and future perspectives.Frontiers in bioengineering and biotechnology · 2026Review
- TRPV6 channel function is involved in endometrial epithelial cell CaCellular and molecular life sciences : CMLS · 2025Article
- Molecular subtype of recurrent implantation failure reveals distinct endometrial etiology of female infertility.Journal of translational medicine · 2025Article
- Organoids as powerful models of endometrium epithelium in transcriptomic, cellular and functional mimicry.Cellular and molecular life sciences : CMLS · 2025Review
- Participation of COX2/mPGES1/PGE2 in mouse and human endometrial stromal decidualization.BMC veterinary research · 2025Article
- Embryo-derived trypsin-induced calcium entry is inhibited by endometrial infertility factor, LEFTY2.Frontiers in cell and developmental biology · 2025Article
- The L-type calcium channel CaV1.3: A potential target for cancer therapy.Journal of cellular and molecular medicine · 2024Review
- Spatiotemporally distinct roles of cyclooxygenase-1 and cyclooxygenase-2 at fetomaternal interface in mice.JCI insight · 2024Article
- Differential expression of ion channel coding genes in the endometrium of women experiencing recurrent implantation failures.Scientific reports · 2024Article
- The epithelial NaCell communication and signaling : CCS · 2024Article
- The histone methyltransferase KMT2D is essential for embryo implantation via regulating precise differentiation of endometrial cells.Cell death discovery · 2024Article
- Therapeutic Potential of Hydrogen Sulfide in Reproductive System Disorders.Biomolecules · 2024Review
- Article
- The co-expression of the depolarizing and hyperpolarizing mechanosensitive ion channels in mammalian retinal neurons.Frontiers in medicine · 2024Article
- Effects of CFTR-ENaC on spinal cord edema after spinal cord injury.Open medicine (Warsaw, Poland) · 2024Article
- RNA sequencing and gene co-expression network ofAnimal reproduction · 2024Article
- Activation of SGK1/ENaC Signaling Pathway Improves the Level of Decidualization in Unexplained Recurrent Spontaneous Abortion.Reproductive sciences (Thousand Oaks, Calif.) · 2023Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.