The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
Human placental metabolic adaptation to chronic hypoxia, high altitude: hypoxic preconditioning
Open accessAbstract
We have previously demonstrated placentas from laboring deliveries at high altitude have lower binding of hypoxia-inducible transcription factor (HIF) to DNA than those from low altitude. It has recently been reported that labor causes oxidative stress in placentas, likely due to ischemic hypoxic insult. We hypothesized that placentas of high-altitude residents acquired resistance, in the course of their development, to oxidative stress during labor. Full-thickness placental tissue biopsies were collected from laboring vaginal and nonlaboring cesarean-section term (37–41 wk) deliveries from healthy pregnancies at sea level and at 3,100 m. After freezing in liquid nitrogen within 5 min of delivery, we quantified hydrophilic and lipid metabolites using 31 P and 1 H NMR metabolomics. Metabolic markers of oxidative stress, increased glycolysis, and free amino acids were present in placentas following labor at sea level, but not at 3,100 m. In contrast, at 3,100 m, the placentas were characterized by the presence of concentrations of stored energy potential (phosphocreatine), antioxidants, and low free amino acid concentrations. Placentas from pregnancies at sea level subjected to labor display evidence of oxidative stress. However, laboring placentas at 3,100 m have little or no oxidative stress at the time of delivery, suggesting greater resistance to ischemia-reperfusion. We postulate that hypoxic preconditioning might occur in placentas that develop at high altitude.
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“Erythropoietin, in particular, is synthesized at rates far higher than the fetal kidney, and may mediate both classical hematopoietic responses to hypoxia and non-classical changes, including increased placental vascularity and defense against oxidative stress (534).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [534]
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“The placental content of glucose and lactate also tend to be lower and higher, respectively, at high relative to low altitude (534).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [534]
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“There is an increase in the fetal arterial concentration of lactate in these fetuses, but little is known about their rate of lactate consumption or about the rates of placental production and delivery of lactate at high altitude (534, 605).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [534]
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“In the human placenta, concentrations of several key essential amino acids were unaffected by altitude, with the exception of glutamine and the antioxidant, taurine, which were higher in concentration at high altitude than sea level (534).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [534]
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“Consistent with this action, the complexes are reduced in these high-altitude placentas (121), as is the ATP/ADP ratio (534), suggesting energetic compromise that could adversely affect transport and synthetic activities of the organ.”
From Placental Origins of Chronic Disease (2016) · cites this paper as [534]
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Metadata
- Authors
- Tissot van Patot, M. C., Murray, A. J., Beckey, V., Cindrova-Davies, T., Johns, J., Zwerdlinger, L., Jauniaux, E., Burton, G. J., & Serkova, N. J.
- Affiliations
- Department of Anesthesiology, University of Colorado Denver Health Sciences Center, Aurora, Colorado;
- University of Cambridge (GB)
- University of Colorado Denver (US)
- Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK;
- The Royal Free Hospital (GB)
- Rocky Mountain Family Practice, Leadville, Colorado
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 2010-01
- Volume
- 298
- Issue
- 1
- Pages
- R166-R172
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- PMC
- PMC2806207
- OpenAlex
- W2113877914
- Cited by
- 107
- References
- 34
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 13 · 2020: 8 · 2019: 6 · 2018: 5 · 2017: 5 · 2016: 8 · 2015: 12 · 2014: 6 · 2013: 7 · 2012: 8
- FWCI
- 4.09
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Wellcome Trust (069027)
- Topics
- Health Sciences › Medicine › Physiology (medical) › High Altitude and Hypoxia
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal and fetal brain pathology
- Keywords
- placenta, high altitude, hypoxic preconditioning, chronic hypoxia, oxidative stress, labor, ischemia-reperfusion, phosphocreatine, antioxidants, free amino acids, glycolysis, placental metabolomics, 31P NMR, 1H NMR
- MeSH terms
- Adaptation, Physiological, Adenosine Diphosphate, Adenosine Triphosphate, Adult, Altitude, Hypoxia, Female, Glycolysis, Humans, Oxygen, Placenta, Pregnancy, Proteins, Reperfusion Injury, Oxidative Stress, Ischemic Preconditioning
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