ArticleeLife2023
Hypoxia-inducible factor 1 signaling drives placental aging and can provoke preterm labor.
Article in eLife, 2023. 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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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- Understanding physiological adaptations of pregnancy to the chronic hypoxia of high altitude to inform obstetrical and neonatal care.Physiological reviews · 2026Review
- m6A-Driven Pexophagy Triggers Placental Ferroptosis to Impair Fetal Growth Upon Environmental Stress.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Inhibition of RIPK1/RIPK3-MLKL inflammatory signaling pathway activation attenuates preterm birth.Cell death discovery · 2026Article
- Morphological Features and HIF1-Dependent Processes in the Brain of Progeny of Female Rats Exposed to Maternal Hypoxia.International journal of molecular sciences · 2026Article
- Reelin regulates the migration and differentiation of extravillous trophoblastic cells.Biological research · 2026Article
- HSP72-AMPK axis mitigates hypoxia-induced cellular senescence to promote colorectal cancer development.Molecular and cellular biochemistry · 2026Article
- Identification of cell senescence-related genes in spontaneous preterm birth based on bioinformatics analysis and machine learning.PloS one · 2026Article
- Short-Term DMOG treatment rejuvenates senescent mesenchymal stem cells by enhancing mitochondrial function and mitophagy through the HIF-1α/BNIP3 pathway.Stem cell research & therapy · 2025Article
- Nuclear Translocation of S100A9 Triggers Senescence of Human Amnion Fibroblasts by De-Repressing LINE1 Via Heterochromatin Erosion at Parturition.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The Association of Placental Grading with Perinatal Outcomes: A Systematic Review and Meta-Analysis.Diagnostics (Basel, Switzerland) · 2025Review
- Impact of Placental Grading on Pregnancy Outcomes: A Retrospective Cohort Study.Healthcare (Basel, Switzerland) · 2025Article
- Article
- Integrating bulk and single-cell transcriptomics to elucidate the role and potential mechanisms of autophagy in aging tissue.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Lysophosphatidylcholine Impairs the Mitochondria Homeostasis Leading to Trophoblast Dysfunction in Gestational Diabetes Mellitus.Antioxidants (Basel, Switzerland) · 2024Article
- Transcriptomic comparison of in vitro models of the human placenta.bioRxiv : the preprint server for biology · 2024Article
- Placental senescence pathophysiology is shared between peripartum cardiomyopathy and preeclampsia in mouse and human.Science translational medicine · 2024Article
- Identification of key metabolism-related genes and pathways in spontaneous preterm birth: combining bioinformatic analysis and machine learning.Frontiers in endocrinology · 2024Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Most cases of preterm labor have unknown cause, and the burden of preterm birth is immense. Placental aging has been proposed to promote labor onset, but specific mechanisms remain elusive. We report findings stemming from unbiased transcriptomic analysis of mouse placenta, which revealed that hypoxia-inducible factor 1 (HIF-1) stabilization is a hallmark of advanced gestational timepoints, accompanied by mitochondrial dysregulation and cellular senescence; we detected similar effects in aging human placenta. In parallel in primary mouse trophoblasts and human choriocarcinoma cells, we modeled HIF-1 induction and demonstrated resultant mitochondrial dysfunction and cellular senescence. Transcriptomic analysis revealed that HIF-1 stabilization recapitulated gene signatures observed in aged placenta. Further, conditioned media from trophoblasts following HIF-1 induction promoted contractility in immortalized uterine myocytes, suggesting a mechanism by which the aging placenta may drive the transition from uterine quiescence to contractility at the onset of labor. Finally, pharmacological induction of HIF-1 via intraperitoneal administration of dimethyloxalyl glycine (DMOG) to pregnant mice caused preterm labor. These results provide clear evidence for placental aging in normal pregnancy, and demonstrate how HIF-1 signaling in late gestation may be a causal determinant of the mitochondrial dysfunction and senescence observed within the trophoblast as well as a trigger for uterine contraction.
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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.