Lung proliferation is dependent on the duration not the timepoint of tracheal occlusion in nitrofen rats with diaphragmatic hernia

Objective: Prenatal tracheal occlusion (TO) promotes lung growth and is applied clinically in fetuses with congenital diaphragmatic hernia (CDH). Limited data are available regarding the effect of duration versus timepoint of TO. Our objective was to document the impact of TO on lung development in the near-term period in rats with nitrofen-induced CDH. Method: Nitrofen was administered on embryonic day (ED)9 and fetal TO was performed on ED18.5, 19, or 20 (term = ED22). Sham-operated and untouched littermates served as controls. Lungs were harvested in 0.5-day steps and only fetuses with a left-sided CDH were included in further analyses. Healthy fetuses provided a reference for normal near-term lung development. Results: Duration of TO in the nitrofen rat model for CDH predicts lung growth in terms of lung-body-weight ratio as well as an increased mRNA level of the proliferation marker Ki67. Longer TO also induced a more complex airway architecture. The timepoint of TO was not predictive of lung growth. Conclusion: In the nitrofen rat model of CDH, a longer period of TO leads to enhanced lung growth and more refined airway architecture. Key points What is already known about this topic? center dot Prenatal tracheal occlusion is investigated as a treatment for pulmonary hypoplasia due to congenital diaphragmatic hernia in humans. Limited information exists on the optimal timepoint and duration of occlusion. What does this study add? center dot In the nitrofen rat model, our study shows that pulmonary development after tracheal occlusion differs with timepoint and duration. It points to enhanced lung proliferation after a longer occlusion period irrespective of the timepoint.

Automated summary

The duration of tracheal occlusion in rats with congenital diaphragmatic hernia can predict lung growth and airway development, while the timepoint of occlusion does not have a significant impact. Prolonged occlusion results in enhanced lung growth, increased cell proliferation, and more refined airway architecture.