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Cited by 114Pregnancy and preeclampsia studiesHigh Altitude and HypoxiaBirth, Development, and Health

Effects of chronic hypoxia in vivo on the expression of human placental glucose transporters

Open access
Zamudio, S., Baumann, M.U., Illsley, N.P.·2006·Placenta
DOI 10.1016/j.placenta.2004.12.010PMC PMC4497571
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Abstract

Birth weight is reduced and the risk of preeclampsia is increased in human high altitude pregnancies. There has been little work to determine whether hypoxia acts directly to reduce fetal growth (e.g. reduced blood flow and oxygen delivery), or via changes in functional capacities such as nutrient transport. We therefore investigated the expression of a primary nutrient transporter, the GLUT1 glucose transporter and two in vitro markers of hypoxia (erythropoietin receptor, EPO-R, and transferrin receptor, TfR) in the syncytial microvillous (MVM) and basal membrane fractions (BMF) of 13 high (3100 m) and 12 low (1600 m) altitude placentas from normal term pregnancies. Birth weight was lower at 3100 m than at 1600 m despite similar gestational age, but none of the infants were clinically designated as fetal growth restriction. EPO-R, TfR and GLUT1 were examined by immunoblotting and maternal circulating erythropoietin and transferrin by ELISA. EPO-R was greater on the MVM (+75%) and BMF (+25%) at 3100 m. TfR was 32% lower on the MVM at 3100 m. GLUT1 was 40% lower in the BMF at 3100 m. Circulating EPO was greater at high altitude, while transferrin was similar, and neither correlated with their membrane receptors. BMF GLUT1 was positively correlated with birth weight at high, but not low altitude. In this in vivo model of chronic placental hypoxia, syncytial EPO-R increased as expected, while nutrient transporters decreased, opposite to what has been observed in vitro. Therefore, hypoxia acts to reduce fetal growth not simply by reducing oxygen delivery, but also by decreasing the density of nutrient transporters.

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  • In the high-altitude human placenta, GLUT1 is reduced at the basal but not the microvillous membranes, consistent with the decreased placental transfer of glucose to the fetus in conditions of chronic maternal hypoxia.

    “By contrast, in the high-altitude human placenta, GLUT1 is reduced at the basal but not the microvillous membranes, consistent with the decreased placental transfer of glucose to the fetus in conditions of chronic maternal hypoxia (601, 605).”

    From Placental Origins of Chronic Disease (2016) · cites this paper as [601]

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  1. [9]Baumann M, Illsley NP. Transferrin receptor and GLUT1 glucose transporter expression are altered in microvillous membrane by cobalt exposure. Placenta. 2001;22:A45. [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Placenta&title=Transferrin%20receptor%20and%20GLUT1%20glucose%20transporter%20expression%20are%20altered%20in%20microvillous%20membrane%20by%20cobalt%20exposure&author=M%20Baumann&author=NP%20Illsley&volume=22&publication_year=2001&pages=A45&)]
  2. [22]Caniggia I, Wu YY, Zamudio S. Overexpression of HIF-1 alpha in placentas from high altitude pregnancies. Placenta. 2002;23:A49. [[Google Scholar](https://scholar.google.com/scholar_lookup?journal=Placenta&title=Overexpression%20of%20HIF-1%20alpha%20in%20placentas%20from%20high%20altitude%20pregnancies&author=I%20Caniggia&author=YY%20Wu&author=S%20Zamudio&volume=23&publication_year=2002&pages=A49&)]

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Authors
Zamudio, S., Baumann, M. U., & Illsley, N. P.
Affiliations
Rutgers New Jersey Medical School (US)
Corresponding author
Zamudio, S.
ORCID
Venue
Placenta
Publisher
Elsevier BV
Published
2006-01
Volume
27
Issue
1
Pages
49-55
ISSN
0143-4004 (ISSN-L)
DOI
10.1016/j.placenta.2004.12.010
PMC
PMC4497571
OpenAlex
W2124038851
Cited by
114
References
34
Citations by year
2026: 4 · 2025: 6 · 2024: 2 · 2022: 4 · 2021: 6 · 2020: 7 · 2019: 6 · 2018: 4 · 2017: 8 · 2016: 6 · 2015: 4 · 2014: 4 · 2013: 9 · 2012: 7
FWCI
7.66
Type
journal article
Language
en
Open access
Licence
Locations
  • Placenta (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Fogarty International Center (R03TW007444)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD042737, HD 42737, HD 46982, R01HD046982)
Topics
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › High Altitude and Hypoxia
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
Keywords
chronic hypoxia, GLUT1 glucose transporter, erythropoietin receptor, transferrin receptor, high-altitude pregnancy, birth weight, fetal growth restriction, syncytiotrophoblast, nutrient transport, erythropoietin, transferrin, preeclampsia
MeSH terms
Adult, Altitude, Altitude Sickness, Hypoxia, Birth Weight, Chronic Disease, Female, Gene Expression Regulation, Humans, Placenta, Pregnancy, Receptors, Transferrin, Receptors, Erythropoietin, Glucose Transporter Type 1

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