ArticleReproduction (Cambridge, England)2021
Implications for preeclampsia: hypoxia-induced Notch promotes trophoblast migration.
Article in Reproduction (Cambridge, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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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
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- PBMC-derived RNA signatures show impaired ability to regulate immune responses in women developing preeclampsia†.Biology of reproduction · 2026Article
- Multi-Omics Reveals Early Pregnancy Placental Dysfunction Associated With Preterm and Term Preeclampsia.MedComm · 2026Article
- HIF-1α mediated placental ischemic signaling in the development of early-onset preeclampsia.Redox biology · 2026Review
- New Frontiers in the Pathophysiology of Hypertensive Pregnancy Disorders: A Systematic Review of Molecular Insights into Preeclampsia.Current issues in molecular biology · 2026Review
- Hypoxia regulates epithelial to mesenchymal transition-associated genes in human trophoblast cells by modulating DNA methylation.PloS one · 2026Article
- [Correlation betweenZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Article
- Hypoxia in extravillous trophoblasts links maternal obesity and offspring neurobehavior.iScience · 2025Article
- Nodal and cripto-1: distinct functions regulate trophoblast specification in mouse pregnancy.Frontiers in cell and developmental biology · 2025Article
- sFlt-1/PlGF and beyond: angiolymphatic-associated signatures and emerging biomarkers in placental pathology.Vascular biology (Bristol, England) · 2025Review
- Simulated ischaemia/reperfusion impairs trophoblast function through divergent oxidative stress- and MMP-9-dependent mechanisms.Bioscience reports · 2024Article
- Review
- Propofol Promoted the Cell Growth and Epithelial Mesenchymal Transformation of the HTR-8/SVneo Cells through Targeting the METTL3 Mediated ZEB2.Reproductive sciences (Thousand Oaks, Calif.) · 2024Article
- Insufficient GDF15 expression predisposes women to unexplained recurrent pregnancy loss by impairing extravillous trophoblast invasion.Cell proliferation · 2023Article
- Mesenchymal stem cell secretome alters gene expression and upregulates motility of human endometrial stromal cells.Reproduction (Cambridge, England) · 2023Article
- Maternal circulating miRNAs contribute to negative pregnancy outcomes by altering placental transcriptome and fetal vascular dynamics.PloS one · 2023Article
- Human Chorionic Villous Differentiation and Placental Development.International journal of molecular sciences · 2022Review
- Gamma Secretase Inhibitors as Potential Therapeutic Targets for Notch Signaling in Uterine Leiomyosarcoma.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
In the first trimester of human pregnancy, low oxygen tension or hypoxia is essential for proper placentation and placenta function. Low oxygen levels and activation of signaling pathways have been implicated as critical mediators in the promotion of trophoblast differentiation, migration, and invasion with inappropriate changes in oxygen tension and aberrant Notch signaling both individually reported as causative to abnormal placentation. Despite crosstalk between hypoxia and Notch signaling in multiple cell types, the relationship between hypoxia and Notch in first trimester trophoblast function is not understood. To determine how a low oxygen environment impacts Notch signaling and cellular motility, we utilized the human first trimester trophoblast cell line, HTR-8/SVneo. Gene set enrichment and ontology analyses identified pathways involved in angiogenesis, Notch and cellular migration as upregulated in HTR-8/SVneo cells exposed to hypoxic conditions. DAPT, a γ-secretase inhibitor that inhibits Notch activation, was used to interrogate the crosstalk between Notch and hypoxia pathways in HTR-8/SVneo cells. We found that hypoxia requires Notch activation to mediate HTR-8/SVneo cell migration, but not invasion. To determine if our in vitro findings were associated with preeclampsia, we analyzed the second trimester chorionic villous sampling (CVS) samples and third trimester placentas. We found a significant decrease in expression of migration and invasion genes in CVS from preeclamptic pregnancies and significantly lower levels of JAG1 in placentas from pregnancies with early-onset preeclampsia with severe features. Our data support a role for Notch in mediating hypoxia-induced trophoblast migration, which may contribute to preeclampsia development.
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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.