ArticleCellular and molecular life sciences : CMLS2018
Downregulation of p53 drives autophagy during human trophoblast differentiation.
Article in Cellular and molecular life sciences : CMLS, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Current approaches and developments in transcript profiling of the human placenta.Human reproduction update · 2020Pooled it
- Review
- Placental plasminogen activator inhibitor 1 is induced by platelet-derived TGF-β independently of TGF-β receptor 3 and is upregulated in preeclampsia.Molecular human reproduction · 2026Article
- Autophagy in PE: Dispute, Role and Potential Target.Cell proliferation · 2025Review
- Blood Pressure and Late Pregnancy Circulating miRNAs in the MADRES Study.Journal of the American Heart Association · 2025Article
- Novel Role of Pin1-Cis P-Tau-ApoE Axis in the Pathogenesis of Preeclampsia and Its Connection with Dementia.Biomedicines · 2024Review
- Autophagy in reproduction and pregnancy-associated diseases.iScience · 2024Review
- The regulated cell death at the maternal-fetal interface: beneficial or detrimental?Cell death discovery · 2024Review
- Regulators involved in trophoblast syncytialization in the placenta of intrauterine growth restriction.Frontiers in endocrinology · 2023Review
- Insight of Autophagy in Spontaneous Miscarriage.International journal of biological sciences · 2022Review
- Chorionic villus-derived mesenchymal stem cell-mediated autophagy promotes the proliferation and invasiveness of trophoblasts under hypoxia by activating the JAK2/STAT3 signalling pathway.Cell & bioscience · 2021Article
- Functional Analysis of p21Cells · 2021Article
- Age and Sex-Related Changes in Human First-Trimester Placenta Transcriptome and Insights into Adaptative Responses to Increased Oxygen.International journal of molecular sciences · 2021Article
- Autophagy Process in Trophoblast Cells Invasion and Differentiation: Similitude and Differences With Cancer Cells.Frontiers in oncology · 2021Review
- Human Placental Trophoblasts Infected byFrontiers in immunology · 2021Article
- Ruminant Placental Adaptation in Early Maternal Undernutrition: An Overview.Frontiers in veterinary science · 2021Review
- Platelet-derived factors impair placental chorionic gonadotropin beta-subunit synthesis.Journal of molecular medicine (Berlin, Germany) · 2020Article
- Placenta-Specific Genes, Their Regulation During Villous Trophoblast Differentiation and Dysregulation in Preterm Preeclampsia.International journal of molecular sciences · 2020Article
- Maternal Obesity Alters Placental Cell Cycle Regulators in the First Trimester of Human Pregnancy: New Insights for BRCA1.International journal of molecular sciences · 2020Article
- The fine-tuning of endoplasmic reticulum stress response and autophagy activation during trophoblast syncytialization.Cell death & disease · 2019Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
The placental barrier is crucial for the supply of nutrients and oxygen to the developing fetus and is maintained by differentiation and fusion of mononucleated cytotrophoblasts into the syncytiotrophoblast, a process only partially understood. Here transcriptome and pathway analyses during differentiation and fusion of cultured trophoblasts yielded p53 signaling as negative upstream regulator and indicated an upregulation of autophagy-related genes. We further showed p53 mRNA and protein levels decreased during trophoblast differentiation. Reciprocally, autophagic flux increased and cytoplasmic LC3B-GFP puncta became more abundant, indicating enhanced autophagic activity. In line, in human first trimester placenta p53 protein mainly localized to the cytotrophoblast, while autophagy marker LC3B as well as late autophagic compartments were predominantly detectable in the syncytiotrophoblast. Importantly, ectopic overexpression of p53 reduced levels of LC3B-II, supporting a negative regulatory role on autophagy in differentiating trophoblasts. This was also shown in primary trophoblasts and human first trimester placental explants, where pharmacological stabilization of p53 decreased LC3B-II levels. In summary our data suggest that differentiation-dependent downregulation of p53 is a prerequisite for activating autophagy in the syncytiotrophoblast.
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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.