University of Oulu

Määttä, J., Sissala, N., Dimova, E., Serpi, R., Moore, L., Koivunen, P. (2018) Hypoxia causes reductions in birth weight by altering maternal glucose and lipid metabolism. Scientific Reports, 8,13583.

Hypoxia causes reductions in birth weight by altering maternal glucose and lipid metabolism

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Author: Määttä, Jenni1; Sissala, Niina1; Dimova, Elitsa Y.1;
Organizations: 1Biocenter Oulu, Faculty of Biochemistry and Molecular Medicine, Oulu Center for Cell-Matrix Research, University of Oulu, Oulu, Finland
2Department of Obstetrics & Gynecology, University of Colorado Denver School of Medicine, Aurora, CO, United States
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2 MB)
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Language: English
Published: Springer Nature, 2018
Publish Date: 2019-01-08


Hypoxia of residence at high altitude (>2500 m) decreases birth weight. Lower birth weight associates with infant mortality and morbidity and increased susceptibility to later-in-life cardiovascular and metabolic diseases. We sought to determine the effects of hypoxia on maternal glucose and lipid metabolism and their contributions to fetal weight. C57BL6/NCrl mice, housed throughout gestation in normobaric hypoxia (15% oxygen) or normoxia, were studied at mid (E9.5) or late gestation (E17.5). Fetal weight at E17.5 was 7% lower under hypoxia than normoxia. The hypoxic compared with normoxic dams had ~20% less gonadal white adipose tissue at mid and late gestation. The hypoxic dams had better glucose tolerance and insulin sensitivity compared with normoxic dams and failed to develop insulin resistance in late gestation. They also had increased glucagon levels. Glucose uptake to most maternal tissues was ~2-fold greater in the hypoxic than normoxic dams. The alterations in maternal metabolism in hypoxia were associated with upregulation of hypoxia-inducible factor (HIF) target genes that serve, in turn, to increase glycolytic metabolism. We conclude that environmental hypoxia alters maternal metabolism by upregulating the HIF-pathway, and suggest that interventions that antagonize such changes in metabolism in high-altitude pregnancy may be helpful for preserving fetal growth.

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Series: Scientific reports
ISSN: 2045-2322
ISSN-E: 2045-2322
ISSN-L: 2045-2322
Volume: 8
Article number: 13583
DOI: 10.1038/s41598-018-31908-2
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Funding: This study was supported by the Academy of Finland Grants 266719 and 308009, the S. Jusélius Foundation, the Emil Aaltonen Foundation and the Jane and Aatos Erkko Foundation to P.K.
Academy of Finland Grant Number: 266719
Detailed Information: 266719 (Academy of Finland Funding decision)
308009 (Academy of Finland Funding decision)
Copyright information: © The Author(s) 2018. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit