ArticlePloS one2014
Preeclampsia is associated with alterations in the p53-pathway in villous trophoblast.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 102 citations in OpenAlex.
- The relationship between Fas and Fas ligand gene polymorphism and preeclampsia risk.Bioscience reports · 2019Pooled it
- Genome-wide transcriptome directed pathway analysis of maternal pre-eclampsia susceptibility genes.PloS one · 2015Trial
- Evolutionary perspectives on endometrial cancer: antagonistic pleiotropy.Molecular & cellular oncology · 2026Review
- The multifactorial role of HDAC9 at the maternal-fetal interface in the pathogenesis of preeclampsia.Clinical science (London, England : 1979) · 2025Review
- Screening and analysis of plasma differential lncRNA/mRNA in early pregnancy of preeclampsia.Malawi medical journal : the journal of Medical Association of Malawi · 2025Article
- Blood Pressure and Late Pregnancy Circulating miRNAs in the MADRES Study.Journal of the American Heart Association · 2025Article
- Article
- Nutraceuticals as Modulators of Molecular Placental Pathways: Their Potential to Prevent and Support the Treatment of Preeclampsia.International journal of molecular sciences · 2024Review
- Antioxidant Defenses, Oxidative Stress Responses, and Apoptosis Modulation in Spontaneous Abortion: An Immunohistochemistry Analysis of First-Trimester Chorionic Villi.Life (Basel, Switzerland) · 2024Article
- MIR193BHG inhibits the proliferation, migration and invasion of trophoblasts by upregulating p53.Experimental and therapeutic medicine · 2024Article
- Safety of embryo cryopreservation: insights from mid-term placental transcriptional changes.Reproductive biology and endocrinology : RB&E · 2024Article
- Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor.Cell communication and signaling : CCS · 2024Article
- Transcriptome analysis of adenomyosis eutopic endometrium reveals molecular mechanisms involved in adenomyosis-related implantation failure and pregnancy disorders.Reproductive biology and endocrinology : RB&E · 2024Article
- Bioinformatics-based Identification of Ferroptosis-related Genes and their Diagnostic Value in Gestational Diabetes Mellitus.Endocrine, metabolic & immune disorders drug targets · 2024Article
- Preeclampsia-associated lncRNA FEZF1-AS1 regulates cell proliferation and apoptosis in placental trophoblast cells through the ELAVL1/NOC2L axis.Cell division · 2023Article
- Gene polymorphisms of cyclin-dependent kinase inhibitor and matrix metalloproteinase-9 in Sudanese patients with esophageal squamous cell carcinoma.Molecular genetics & genomic medicine · 2022Article
- Low-dose aspirin inhibits trophoblast cell apoptosis by activating the CREB/Bcl-2 pathway in pre-eclampsia.Cell cycle (Georgetown, Tex.) · 2022Article
- Markers of Endothelial Dysfunction Are Attenuated by Resveratrol in Preeclampsia.Antioxidants (Basel, Switzerland) · 2022Article
- Ferroptosis-Related Proteins Are Potential Diagnostic Molecular Markers for Patients with Preeclampsia.Biology · 2022Article
- MicroRNA-495 suppresses pre-eclampsia via activation of p53/PUMA axis.Cell death discovery · 2022Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundPreeclampsia (PE) is characterized by exaggerated apoptosis of the villous trophoblast of placental villi. Since p53 is a critical regulator of apoptosis we hypothesized that excessive apoptosis in PE is mediated by abnormal expression of proteins participating in the p53 pathway and that modulation of the p53 pathway alters trophoblast apoptosis in vitro.
methodsFresh placental villous tissue was collected from normal pregnancies and pregnancies complicated by PE; Western blotting and real-time PCR were performed on tissue lysate for protein and mRNA expression of p53 and downstream effector proteins, p21, Bax and caspases 3 and 8. To further assess the ability of p53 to modulate apoptosis within trophoblast, BeWo cells and placental villous tissue were exposed to the p53-activator, Nutlin-3, alone or in combination with the p53-inhibitor, Pifithrin-α (PFT-α). Equally, Mdm2 was knocked-down with siRNA.
resultsProtein expression of p53, p21 and Bax was significantly increased in pregnancies complicated by PE. Conversely, Mdm2 protein levels were significantly depleted in PE; immunohistochemistry showed these changes to be confined to trophoblast. Reduction in the negative feedback of p53 by Mdm2, using siRNA and Nutlin-3, caused an imbalance between p53 and Mdm2 that triggered apoptosis in term villous explants. In the case of Nutlin, this was attenuated by Pifithrin-α.
conclusionsThese data illustrate the potential for an imbalance in p53 and Mdm2 expression to promote excessive apoptosis in villous trophoblast. The upstream regulation of p53 and Mdm2, with regard to exaggerated apoptosis and autophagy in PE, merits further investigation.
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