Influence of prenatal hypoxia and postnatal hyperoxia on morphologic lung maturation in mice

Andreas Schmiedl; Torge Roolfs; Erol Tutdibi; Ludwig Gortner; Dominik Monz

doi:10.1371/journal.pone.0175804

Influence of prenatal hypoxia and postnatal hyperoxia on morphologic lung maturation in mice

PLoS One. 2017 Apr 20;12(4):e0175804. doi: 10.1371/journal.pone.0175804. eCollection 2017.

Authors

Andreas Schmiedl^{1

2

3}, Torge Roolfs¹, Erol Tutdibi⁴, Ludwig Gortner⁴, Dominik Monz⁴

Affiliations

¹ Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.
² Biomedical Research in Endstage und Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover Medical School, Hannover, Germany.
³ REBIRTH Cluster of Excellence, Hannover Medical School, Hannover, Germany.
⁴ Department of Pediatrics and Neonatology, Saarland University, Homburg/Saar, Germany.

Abstract

Background: Oxygen supply as a lifesaving intervention is frequently used to treat preterm infants suffering additionally from possible prenatal or perinatal pathogen features. The impact of oxygen and/or physical lung injury may influence the morphological lung development, leading to a chronic postnatal lung disease called bronchopulmonary dysplasia (BPD). At present different experimental BPD models are used. However, there are no systematic comparative studies regarding different influences of oxygen on morphological lung maturation.

Objective: We investigated the influence of prenatal hypoxia and/or postnatal hyperoxia on morphological lung maturation based on stereological parameters, to find out which model best reflects morphological changes in lung development comparable with alterations found in BPD.

Methods: Pregnant mice were exposed to normoxia, the offspring to normoxia (No/No) or to hyperoxia (No/Hyper). Furthermore, pregnant mice were exposed to hypoxia and the offspring to normoxia (Hypo/No) or to hyperoxia (Hypo/Hyper). Stereological investigations were performed on all pups at 14 days after birth.

Results: Compared to controls (No/No) 1) the lung volume was significantly reduced in the No/Hyper and Hypo/Hyper groups, 2) the volume weighted mean volume of the parenchymal airspaces was significantly higher in the Hypo/Hyper group, 3) the total air space volume was significantly lower in the No/Hyper and Hypo/Hyper groups, 4) the total septal surface showed significantly lower values in the No/Hyper and Hypo/Hyper groups, 5) the wall thickness of septa showed the highest values in the Hypo/Hyper group without reaching significance, 6) the volume density and the volume weighted mean volume of lamellar bodies in alveolar epithelial cells type II (AEII) were significantly lower in the Hypo/Hyper group.

Conclusion: Prenatal hypoxia and postnatal hyperoxia differentially influence the maturation of lung parenchyma. In 14 day old mice a significant retardation of morphological lung development leading to BPD-like alterations indicated by different parameters was only seen after hypoxia and hyperoxia.

MeSH terms

Animals
Female
Hyperoxia / pathology*
Hypoxia / pathology*
Lung / embryology*
Lung / pathology
Mice
Mice, Inbred C57BL
Pregnancy

Grants and funding

This work was in part supported by the Sino-German Center for Research Promotion, by the Federal Ministry for Education and Research (BMBF) via the German Center for Lung Research (DZL) as well as by the German Research Federation (DFG) via the Cluster of Excellence REBIRTH. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. No additional external funding received for this study.