ArticleJournal of molecular medicine (Berlin, Germany)2018
LEFTY2 inhibits endometrial receptivity by downregulating Orai1 expression and store-operated Ca
Article in Journal of molecular medicine (Berlin, Germany), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Molecular signature of human endometrial stem/progenitor cells at the single-cell level.Stem cell reports · 2026Article
- Spatial Transcriptomics of Human Decidua Identifies Molecular Signatures in Recurrent Pregnancy Loss.Genomics, proteomics & bioinformatics · 2026Article
- The Therapeutic Potential of Lactobacillus crispatus for Chronic Endometritis: A Comprehensive Clinical Trial and Experimental Investigation.Probiotics and antimicrobial proteins · 2025Article
- Calcium Homeostasis Machinery in the Human Uterus-A Potential Therapeutic Target in Endometrial Cancer.International journal of molecular sciences · 2025Review
- Embryo-derived trypsin-induced calcium entry is inhibited by endometrial infertility factor, LEFTY2.Frontiers in cell and developmental biology · 2025Article
- Rel Family Transcription Factor NFAT5 Upregulates COX2 via HIF-1α Activity in Ishikawa and HEC1a Cells.International journal of molecular sciences · 2024Article
- CREB1 Is Involved in miR-134-5p-Mediated Endometrial Stromal Cell Proliferation, Apoptosis, and Autophagy.Cells · 2023Article
- Multiomics Studies Investigating Recurrent Pregnancy Loss: An Effective Tool for Mechanism Exploration.Frontiers in immunology · 2022Review
- Podocalyxin promotes an impermeable epithelium and inhibits pro-implantation factors to negatively regulate endometrial receptivity.Scientific reports · 2021Article
- Single-cell transcriptome analysis reveals defective decidua stromal niche attributes to recurrent spontaneous abortion.Cell proliferation · 2021Article
- High-grade serous tubo-ovarian cancer refined with single-cell RNA sequencing: specific cell subtypes influence survival and determine molecular subtype classification.Genome medicine · 2021Article
- WNT4 Balances Development vs Disease in Gynecologic Tissues and Women's Health.Endocrinology · 2021Review
- Annexin A7 Regulates Endometrial Receptivity.Frontiers in cell and developmental biology · 2020Article
- The effect of GnRH antagonist cetrorelix on Wnt signaling members in pubertal and adult mouse ovaries.Histochemistry and cell biology · 2019Article
- Construction of implantation failure related lncRNA-mRNA network and identification of lncRNA biomarkers for predicting endometrial receptivity.International journal of biological sciences · 2018Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Early embryo development and endometrial differentiation are initially independent processes, and synchronization, imposed by a limited window of implantation, is critical for reproductive success. A putative negative regulator of endometrial receptivity is LEFTY2, a member of the transforming growth factor (TGF)-β family. LEFTY2 is highly expressed in decidualizing human endometrial stromal cells (HESCs) during the late luteal phase of the menstrual cycle, coinciding with the closure of the window of implantation. Here, we show that flushing of the uterine lumen in mice with recombinant LEFTY2 inhibits the expression of key receptivity genes, including Cox2, Bmp2, and Wnt4, and blocks embryo implantation. In Ishikawa cells, a human endometrial epithelial cell line, LEFTY2 downregulated the expression of calcium release-activated calcium channel protein 1, encoded by ORAI1, and inhibited store-operated Ca KEY MESSAGES: •Endometrial receptivity is negatively regulated by LEFTY2. •LEFTY2 inhibits the expression of key murine receptivity genes, including Cox2, Bmp2 and Wnt4, and blocks embryo implantation. •LEFTY2 downregulates the expression of Orai1 and inhibits SOCE. •LEFTY2 and the Orai1 blockers 2-APB, MRS-1845, and YM-58483 inhibit COX2, BMP2, and WNT4 expression in endometrial cells. •Targeting LEFTY2 and Orai1 may represent a novel approach for treating unexplained infertility.
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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.