ArticleThe Journal of clinical investigation2018
HIF2α in the uterine stroma permits embryo invasion and luminal epithelium detachment.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 95 citations in OpenAlex.
- Differential Expression and Function of Arginase in Mouse Uterus During Early Pregnancy.International journal of molecular sciences · 2026Article
- Real-time intrauterine dissolved oxygen dynamics across the luteal phase: a potential non-invasive functional biomarker of endometrial status.Reproductive biology and endocrinology : RB&E · 2026Observational
- HIF2α-induced lysyl oxidase safeguards successful pregnancy by remodelling collagens at the feto-maternal interface.Cell death & disease · 2026Article
- Divergent Roles of HIF-1α and HIF-2α in Embryonic Development and Early Pregnancy.International journal of molecular sciences · 2026Review
- Identified endoplasmic reticulum stress-related molecular cluster and immune characterization in endometriosis.Scientific reports · 2025Article
- Blastocyst-Secreted miR-519d-3p Modulated the Cell Viability, Apoptosis and Migration of Human Endometrial Stromal Cells by Targeting HIF1α.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- Hypoxia-driven circ-TBC1D1/miR-520h/EPHB4 impairs trophoblast function in unexplained recurrent spontaneous abortion.Scientific reports · 2025Article
- An ex vivo uterine system captures implantation, embryogenesis, and trophoblast invasion via maternal-embryonic signaling.Nature communications · 2025Article
- Establishment of an in vitro implantation model using a newly developed mouse endometrial organoid.Development (Cambridge, England) · 2025Article
- Limiting Premenstrual Endometrial Hypoxia Inducible Factor 2 Alpha May Fine-Tune Endometrial Function at Menstruation.The Journal of clinical endocrinology and metabolism · 2025Article
- Endometrial zinc transporterPNAS nexus · 2025Article
- Spatiotemporal functions of leukemia inhibitory factor in embryo attachment and implantation chamber formation.Cell death discovery · 2024Article
- Unexpected nuclear hormone receptor and chromatin dynamics regulate estrous cycle dependent gene expression.Nucleic acids research · 2024Article
- Pilot Study on the Effect of Patient Condition and Clinical Parameters on Hypoxia-Induced Factor Expression:International journal of molecular sciences · 2024Article
- Spatiotemporally distinct roles of cyclooxygenase-1 and cyclooxygenase-2 at fetomaternal interface in mice.JCI insight · 2024Article
- Exposure to a Low-Oxygen Environment Causes Implantation Failure and Transcriptomic Shifts in Mouse Uteruses and Ovaries.Biomedicines · 2024Article
- The regulated cell death at the maternal-fetal interface: beneficial or detrimental?Cell death discovery · 2024Review
- Article
- Placental homing peptide guides HIF1α‑silenced exosomes conjugates for targeted enhancement of invasion of trophoblast cells.Molecular medicine reports · 2023Article
- The EZH2-PRC2-H3K27me3 axis governs the endometrial cell cycle and differentiation for blastocyst invasion.Cell death & disease · 2023Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although it has been reported that hypoxia inducible factor 2 α (Hif2a), a major transcriptional factor inducible by low oxygen tension, is expressed in the mouse uterus during embryo implantation, its role in pregnancy outcomes remains unclear. This study aimed to clarify functions of uterine HIF using transgenic mouse models. Mice with deletion of Hif2a in the whole uterus (Hif2a-uKO mice) showed infertility due to implantation failure. Supplementation with progesterone (P4) and leukemia inhibitory factor (LIF) restored decidual growth arrest and aberrant position of implantation sites in Hif2a-uKO mice, respectively, but did not rescue pregnancy failure. Histological analyses in Hif2a-uKO mice revealed persistence of the intact luminal epithelium, which blocked direct contact between stroma and embryo, inactivation of PI3K-AKT pathway (embryonic survival signal), and failed embryo invasion. Mice with stromal deletion of Hif2a (Hif2a-sKO mice) showed infertility with impaired embryo invasion and those with epithelial deletion of Hif2a (Hif2a-eKO mice) showed normal fertility, suggesting the importance of stromal HIF2α in embryo invasion. This was reflected in reduced expression of membrane type 2 metalloproteinase (MT2-MMP), lysyl oxidase (LOX), VEGF, and adrenomedullin (ADM) in Hif2a-uKO stroma at the attachment site, suggesting that stromal HIF2α regulates these mediators to support blastocyst invasion. These findings provide new insight that stromal HIF2α allows trophoblast invasion through detachment of the luminal epithelium and activation of an embryonic survival signal.
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