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Gestational chronic intermittent hypoxia induces hypertension, proteinuria, and fetal growth restriction in mice

  • Sleep Breathing Physiology and Disorders • Original Article
  • Published:
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A Correction to this article was published on 12 February 2022

This article has been updated

Abstract

Purpose

Pregnant women are predisposed to obstructive sleep apnea (OSA). Based on the fact that OSA is an independent risk factor for hypertension among the general population, we hypothesized that chronic intermittent hypoxia (CIH), as a feature of OSA, may lead to preeclampsia.

Methods

Pregnant and non-pregnant C57BL/6 J mice were exposed to two conditions of chronic intermittent hypoxia: CIH1 (21–5% O2 alternations), CIH2 (21–10% O2 alternations), and room air until day 19.

Results

In non-pregnant mice, compared with their respective baseline values, systolic blood pressure (SBP) started to rise from day 14 in the CIH1 group, and SBP rose until day 19 in the CIH2 group. Compared with the pregnant mice exposed to room air, pregnant mice exposed to CIH1 maintained elevated SBP from day 14, accompanied by proteinuria, fetal and placental growth restriction, and a reduction in the number of fetuses. An imbalance between proangiogenic and antiangiogenic factors and impairment of vascular remodeling existed in the placenta of pregnant mice exposed to CIH1. Maternal serum levels of the soluble form of vascular endothelial growth factor receptor-1 were also significantly increased. Pregnant mice exposed to CIH2 seemed to have milder changes than pregnant mice exposed to CIH1.

Conclusion

Our results demonstrated that gestational CIH may induce gestational hypertension, proteinuria, fetal and placental growth restriction as well as impairments in placental angiogenesis and vascular remodeling.

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Abbreviations

OSA:

Obstructive sleep apnea

CIH:

Chronic intermittent hypoxia

VEGF:

Vascular endothelial growth factor

VEGFR:

Vascular endothelial growth factor receptor

Flk1:

Vascular endothelial growth factor receptor-2

sFlt-1:

Soluble form of vascular endothelial growth factor receptor-1

PIH1 group:

CIH1 (21–5%O2 alternations) group of pregnancy

PC group:

Group of pregnancy

PIH2 group:

CIH2 (21–10%O2 alternations) group of pregnancy

NC group:

Group of non-pregnancy

NIH1 group:

IH1 group of non-pregnancy

NIH2 group:

IH2 group of non-pregnancy

SBP:

Systolic blood pressure

BP:

Blood pressure

Flt-1:

Vascular endothelial growth factor receptor-1

Ang-1:

Angiopoietin-1

Ang-2:

Angiopoietin-2

Tie-1:

Tyrosine kinase with immunoglobulin-like and EGF-like domains-1

Tie-2:

Tyrosine kinase with immunoglobulin-like and EGF-like domains-2

α-SMA:

α-Smooth muscle actin

SD:

Standard deviation

ECs:

Endothelial cells

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Funding

This work was supported by the Natural Science Foundation of Fujian Province (Grant No 2020J011095) and the National Natural Science Foundation of China (No.81301995). The funders had no role in study design, data collection and analysis, decision to publish. Cuilian Weng got the funds.

Author information

Author notes

  1. Cuilian Weng, Long Huang and Hangwei Feng contributed equally to this work.

Authors and Affiliations

  1. Department of Critical Care Medicine, Fujian Provincial Hospital South Branch, The Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian Province, China

    Cuilian Weng, Long Huang, Hangwei Feng, Xingsheng Lin, Jian Lin & Xincai Wang

  2. Department of Respirology, Peking University People’s Hospital, Beijing, China

    Quanying He

  3. Department of Pharmacy, Fujian Provincial Hospital South Branch, The Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian Province, China

    Tingting Jiang

  4. Department of Otorhinolaryngology, Fujian Provincial Hospital, The Shengli Clinical Medical College of Fujian Medical University, Fujian Medical University, 134 Dongjie Street, Fuzhou, Fujian Province, China

    Qinghua Liu

Authors
  1. Cuilian Weng
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  2. Long Huang
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  3. Hangwei Feng
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  7. Jian Lin
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  8. Xincai Wang
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  9. Qinghua Liu
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Contributions

Conceptualization: Cuilian Weng, Quanying He, Qinghua Liu; methodology: Hangwei Feng, Xincai Wang; formal analysis and investigation: Xingsheng Lin, Tingting Jiang, Jian Lin; writing—original draft preparation: Cuilian Weng, Long Huang; writing—review and editing: Cuilian Weng, Qinghua Liu; funding acquisition: Cuilian Weng; supervision: Quanying He, Qinghua Liu.

Corresponding author

Correspondence to Qinghua Liu.

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Ethics approval

Animal care and all of the experimental procedures executed in this study were approved by the Animal Ethic Committee of Perking University.

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The authors declare no competing interests.

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The original online version of this article was revised: Figure 2B in the original version of this article is not correct. The correct figure is shown here. The authors wish to apologize for this error.

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Weng, C., Huang, L., Feng, H. et al. Gestational chronic intermittent hypoxia induces hypertension, proteinuria, and fetal growth restriction in mice. Sleep Breath 26, 1661–1669 (2022). https://doi.org/10.1007/s11325-021-02529-3

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  • DOI: https://doi.org/10.1007/s11325-021-02529-3

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