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

Sleep Breath. 2022 Dec;26(4):1661-1669. doi: 10.1007/s11325-021-02529-3. Epub 2021 Nov 29.

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.

Keywords: Intermittent hypoxia; Obstructive; Preeclampsia; Sleep apnea.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Female
  • Fetal Growth Retardation / metabolism
  • Humans
  • Hypertension* / complications
  • Hypoxia
  • Mice
  • Mice, Inbred C57BL
  • Placenta / metabolism
  • Pregnancy
  • Proteinuria / etiology
  • Proteinuria / metabolism
  • Sleep Apnea, Obstructive*
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Remodeling

Substances

  • Vascular Endothelial Growth Factor A