University of Oulu

Sissala, N., Myllymäki, E., Mohr, F., Halmetoja, R., Kuvaja, P., Dimova, E. Y., & Koivunen, P. (2022). Hypoxia ameliorates maternal diet‐induced insulin resistance during pregnancy while having a detrimental effect on the placenta. Physiological Reports, 10(9).

Hypoxia ameliorates maternal diet-induced insulin resistance during pregnancy while having a detrimental effect on the placenta

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Author: Sissala, Niina1; Myllymäki, Elisa1; Mohr, Florian1;
Organizations: 1Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, Oulu Center for Cell-Matrix Research, University of Oulu, Oulu, Finland
2Finnish Institute for Health and Welfare, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 14.1 MB)
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Language: English
Published: John Wiley & Sons, 2022
Publish Date: 2023-02-28


Maternal overweight/obesity contributes significantly to the development of gestational diabetes, which causes risks to both mother and fetus and is increasing sharply in prevalence worldwide. Since hypoxia reprograms energy metabolism and can alleviate weight gain, adiposity, insulin resistance (IR), and dyslipidemia, we set out to study the potential of sustained reduced ambient oxygen tension (15% O2) during pregnancy for alleviating the detrimental effects of diet-induced IR in C57Bl/6N mice, taking normal chow-fed and normoxia (21% O2) groups as controls. Our data show that hypoxic intervention reduced maternal weight gain, adiposity, and adipose tissue inflammation, and ameliorated maternal glucose metabolism and IR during gestation in diet-induced IR relative to normoxia. Where diet-induced IR reduced maternal hemoglobin and increased serum erythropoietin levels, hypoxic intervention compensated for these changes. Diet-induced IR reduced fetal growth in normoxia, and even more in hypoxia. Hypoxic intervention reduced liver weight gain during pregnancy in the dams with diet-induced IR, maternal liver weight being positively associated with embryo number. In case of diet-induced IR, the hypoxic intervention compromised placental energy metabolism and vascularization and increased end-pregnancy placental necrosis. Altogether, these data show that although hypoxic intervention mediates several beneficial effects on maternal metabolism, the combination of it with diet-induced IR is even more detrimental to the placental and fetal outcome than diet-induced IR alone.

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Series: Physiological reports
ISSN: 2051-817X
ISSN-E: 2051-817X
ISSN-L: 2051-817X
Volume: 10
Issue: 9
Article number: e15302
DOI: 10.14814/phy2.15302
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 (Grant 308009 to P.K.), the Sigrid Jusélius Foundation (P.K.) and the Jane and Aatos Erkko Foundation (P.K.).
Academy of Finland Grant Number: 308009
Detailed Information: 308009 (Academy of Finland Funding decision)
Copyright information: © 2022 The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.