ArticleThe Journal of clinical investigation2014
Endometrial VEGF induces placental sFLT1 and leads to pregnancy complications.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
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Who cites it
103 citing papers in PubMed, 187 citations in OpenAlex.
- Article
- Review
- Human tissue-resident CD8 T cells contribute to trophoblast homeostasis in health and during acute inflammation.bioRxiv : the preprint server for biology · 2026Article
- Neuropilin 1 (NRP1) conveys SEMA3A signals to restrict physiological angiogenesis.Angiogenesis · 2026Article
- Aberrant Uteroplacental and Vascular Signaling and Remodeling by Matrix Metalloproteinases in Pregnancy-Related Hypertension and Preeclampsia.Biomolecules · 2026Review
- Single-cell RNA sequencing of leukocytes at the maternal-fetal interface in physiological and pathological Nodal-deficient pregnancies.Frontiers in immunology · 2026Article
- Transcriptome Analysis, Machine Learning, and Experimental Identification of CDK7 Affecting the Progression of Pregnancy-induced Hypertension by Influencing Macrophage Polarization.Current molecular medicine · 2026Article
- VEGFR1 as a Target for Cardiovascular Gene Therapy.Journal of cardiovascular translational research · 2025Review
- Maternal Diet-Induced Excess Adiposity in Mice Disrupts Mid-Gestation Decidual Immune and Vascular Homeostasis Without Impairing Spiral Artery Remodeling.Acta physiologica (Oxford, England) · 2025Article
- Article
- Loss of Inhibin Negative Feedback to Pituitary Gonadotropes Leads to Enhanced Ovulation but Pregnancy Failure in Mice.Endocrinology · 2025Article
- Identification of transcription factors that regulate placental sFLT1 expression.Molecular human reproduction · 2025Article
- Placental RTN3L-dependent ER-Phagy Contributes to Fetal Testicular Dysplasia Upon Environmental Stress.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- Genetic Variants Associated With Preeclampsia and Maternal Serum sFLT1 Levels.Hypertension (Dallas, Tex. : 1979) · 2025Article
- Spatiotemporal Angiogenic Patterns in the Development of the Mouse Fetal Blood-Brain Barrier System During Pregnancy.International journal of molecular sciences · 2025Article
- Super-Enhancers in Placental Development and Diseases.Journal of developmental biology · 2025Review
- Impacts of Gestational F-53B Exposure on Fetal Neurodevelopment: Insights from Placental and Thyroid Hormone Disruption.Environment & health (Washington, D.C.) · 2025Article
- Article
- Whole transcriptome analysis and preliminary construction of ceRNA networks in obstetric antiphospholipid syndrome.Frontiers in immunology · 2025Article
43 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
14 authors at 6 institutions in 2 countries.
Funding
Abstract
There is strong evidence that overproduction of soluble fms-like tyrosine kinase-1 (sFLT1) in the placenta is a major cause of vascular dysfunction in preeclampsia through sFLT1-dependent antagonism of VEGF. However, the cause of placental sFLT1 upregulation is not known. Here we demonstrated that in women with preeclampsia, sFLT1 is upregulated in placental trophoblasts, while VEGF is upregulated in adjacent maternal decidual cells. In response to VEGF, expression of sFlt1 mRNA, but not full-length Flt1 mRNA, increased in cultured murine trophoblast stem cells. We developed a method for transgene expression specifically in mouse endometrium and found that endometrial-specific VEGF overexpression induced placental sFLT1 production and elevated sFLT1 levels in maternal serum. This led to pregnancy losses, placental vascular defects, and preeclampsia-like symptoms, including hypertension, proteinuria, and glomerular endotheliosis in the mother. Knockdown of placental sFlt1 with a trophoblast-specific transgene caused placental vascular changes that were consistent with excess VEGF activity. Moreover, sFlt1 knockdown in VEGF-overexpressing animals enhanced symptoms produced by VEGF overexpression alone. These findings indicate that sFLT1 plays an essential role in maintaining vascular integrity in the placenta by sequestering excess maternal VEGF and suggest that a local increase in VEGF can trigger placental overexpression of sFLT1, potentially contributing to the development of preeclampsia and other pregnancy complications.
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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.