Short-term perinatal oxygen exposure may impair lung development in adult mice

Vasantha H S Kumar,Lori Nielsen,Huamei Wang

doi:10.1186/s40659-020-00318-y

Vasantha H S Kumar, Lori Nielsen + Show 1 more

Open Access

https://doi.org/10.1186/s40659-020-00318-y

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Abstract

BackgroundHyperoxia at resuscitation increases oxidative stress, and even brief exposure to high oxygen concentrations during stabilization may trigger organ injury with adverse long-term outcomes in premature infants. We studied the long-term effects of short-term perinatal oxygen exposure on cell cycle gene expression and lung growth in adult mice.MethodsWe randomized mice litters at birth to 21, 40, or 100%O2 for 30 min and recovered in room air for 4 or 12 weeks. Cell cycle gene expression, protein analysis, and lung morphometry were assessed at 4 and 12 weeks.ResultsThe principal component analysis demonstrated a high degree of correlation for cell cycle gene expression among the three oxygen groups. Lung elastin was significantly lower in the 100%O2 groups at 4 weeks. On lung morphometry, radial alveolar count, alveolar number, and septal count were similar. However, the mean linear intercept (MLI) and septal length significantly correlated among the oxygen groups. The MLI was markedly higher in the 100%O2 groups at 4 and 12 weeks of age, and the septal length was significantly lower in the 100%O2 groups at 12 weeks.ConclusionShort-term exposure to high oxygen concentrations lead to subtle changes in lung development that may affect alveolarization. The changes are related explicitly to secondary crest formation that may result in alteration in lung elastin. Resuscitation with high oxygen concentrations may have a significant impact on lung development and long-term outcomes such as BPD in premature infants.

Highlights

Hyperoxia at resuscitation increases oxidative stress, and even brief exposure to high oxygen concentrations during stabilization may trigger organ injury with adverse long-term outcomes in premature infants
We focused on cell cycle gene expression and its impact on cell proliferation and lung development, one of the critical components of responses to hyperoxia
The study demonstrates that short-term exposure to high oxygen concentrations leads to subtle changes in lung development that may affect alveolarization

Summary

Introduction

Hyperoxia at resuscitation increases oxidative stress, and even brief exposure to high oxygen concentrations during stabilization may trigger organ injury with adverse long-term outcomes in premature infants. There is uncertainty as to whether initiating resuscitation post-birth with lower (FiO2 < 0.40) or higher (FiO2 ≥ 0.40) in the first ten minutes of birth has on mortality, morbidity, and other long-term outcomes in premature infants [8, 9]. Current neonatal resuscitation guidelines recommend initiation of resuscitation with low oxygen (FiO2: 0.21–0.30) and to titrate the oxygen concentration to achieve preductal oxygen saturation approximating the interquartile range measured in healthy term infants [10]. Due to concerns about oxidative injury, the guidelines do not recommend initiation of resuscitation with ≥ 65%O2 [10].

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