ArticlePloS one2010
Abnormalities in oxygen sensing define early and late onset preeclampsia as distinct pathologies.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 110 citations in OpenAlex.
- HIF1-α induces mitochondrial fission in trophoblastic cells during early pregnancy and in preeclampsia.iScience · 2026Article
- HIF-1A Expression in Placenta of Pregnancies Complicated with Preeclampsia and Fetal Growth Restriction.Diagnostics (Basel, Switzerland) · 2025Article
- Streamlined Analysis of Maternal Plasma Indicates Small Extracellular Vesicles are Significantly Elevated in Early-Onset Preeclampsia.Reproductive sciences (Thousand Oaks, Calif.) · 2024Article
- iPSC-based modeling of preeclampsia identifies epigenetic defects in extravillous trophoblast differentiation.iScience · 2024Article
- Hypoxia Inducible Factors (HIF1α and HIF3α) are differentially methylated in preeclampsia placentae and are associated with birth outcomes.Molecular and cellular biochemistry · 2023Article
- CaInternational journal of molecular sciences · 2023Review
- Expression of placental glycans and its role in regulating peripheral blood NK cells during preeclampsia: a perspective.Frontiers in endocrinology · 2023Review
- Significance of placental CD200 expression in patients with preeclampsia: Comparison between early‑ and late‑onset patients.Molecular medicine reports · 2023Article
- HIF1 inhibitor acriflavine rescues early-onset preeclampsia phenotype in mice lacking placental prolyl hydroxylase domain protein 2.JCI insight · 2022Article
- Hypoxia-Inducible Factor 1 and Preeclampsia: A New Perspective.Current hypertension reports · 2022Review
- Hypoxia-Reoxygenation Impairs Autophagy-Lysosomal Machinery in Primary Human Trophoblasts Mimicking Placental Pathology of Early-Onset Preeclampsia.International journal of molecular sciences · 2022Article
- Dysregulation of Oxygen Sensing/Response Pathways in Pregnancies Complicated by Idiopathic Intrauterine Growth Restriction and Early-Onset Preeclampsia.International journal of molecular sciences · 2022Article
- Dichotomy in hypoxia-induced mitochondrial fission in placental mesenchymal cells during development and preeclampsia: consequences for trophoblast mitochondrial homeostasis.Cell death & disease · 2022Article
- Hypoxia and the integrated stress response promote pulmonary hypertension and preeclampsia: Implications in drug development.Drug discovery today · 2021Review
- Could Vitamin D Be Effective in Prevention of Preeclampsia?Nutrients · 2021Review
- The Role of Leptin in Fetal Growth during Pre-Eclampsia.International journal of molecular sciences · 2021Review
- Current State of Preeclampsia Mouse Models: Approaches, Relevance, and Standardization.Frontiers in physiology · 2021Review
- Tracking placental development in health and disease.Nature reviews. Endocrinology · 2020Review
- The Critical Roles of the SUMO-Specific Protease SENP3 in Human Diseases and Clinical Implications.Frontiers in physiology · 2020Review
- Hypoxia-induced Downregulation of SRC-3 Suppresses Trophoblastic Invasion and Migration Through Inhibition of the AKT/mTOR Pathway: Implications for the Pathogenesis of Preeclampsia.Scientific reports · 2019Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundThe pathogenesis of preeclampsia, a serious pregnancy disorder, is still elusive and its treatment empirical. Hypoxia Inducible Factor-1 (HIF-1) is crucial for placental development and early detection of aberrant regulatory mechanisms of HIF-1 could impact on the diagnosis and management of preeclampsia. HIF-1α stability is controlled by O(2)-sensing enzymes including prolyl hydroxylases (PHDs), Factor Inhibiting HIF (FIH), and E3 ligases Seven In Absentia Homologues (SIAHs). Here we investigated early- (E-PE) and late-onset (L-PE) human preeclamptic placentae and their ability to sense changes in oxygen tension occurring during normal placental development. METHODS AND
findingsExpression of PHD2, FIH and SIAHs were significantly down-regulated in E-PE compared to control and L-PE placentae, while HIF-1α levels were increased. PHD3 expression was increased due to decreased FIH levels as demonstrated by siRNA FIH knockdown experiments in trophoblastic JEG-3 cells. E-PE tissues had markedly diminished HIF-1α hydroxylation at proline residues 402 and 564 as assessed with monoclonal antibodies raised against hydroxylated HIF-1α P402 or P564, suggesting regulation by PHD2 and not PHD3. Culturing villous explants under varying oxygen tensions revealed that E-PE, but not L-PE, placentae were unable to regulate HIF-1α levels because PHD2, FIH and SIAHs did not sense a hypoxic environment.
conclusionDisruption of oxygen sensing in E-PE vs. L-PE and control placentae is the first molecular evidence of the existence of two distinct preeclamptic diseases and the unique molecular O(2)-sensing signature of E-PE placentae may be of diagnostic value when assessing high risk pregnancies and their severity.
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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.