Maternal administration of betamethasone inhibits proliferation induced by fetal tracheal occlusion in the nitrofen rat model for congenital diaphragmatic hernia: a placebo-controlled study

Abstract

Purpose: Fetal tracheal occlusion (TO) is offered to fetuses with severe pulmonary hypoplasia due to congenital diaphragmatic hernia (CDH). TO induces lung growth, but even when performed minimally invasive, there is a risk for iatrogenic preterm delivery. Whenever this is anticipated, maternal glucocorticoids (GC) may be given to enhance lung maturation. The pulmonary effects of GC in fetuses with CDH that underwent TO are yet poorly defined. Therefore, we conducted a placebo-controlled study in the nitrofen (NF) rat model for CDH.

Methods: Pregnant rats were gavage fed NF or olive oil (OO) on ED9.5. At ED19.0, fetuses were either assigned to TO or left untouched. Maternal betamethasone (BM) or saline (PLAC) was administered on ED20. Necropsy was done on ED21.5 to obtain lung-to-body-weight ratio (LBWR), and perform quantitative RT-PCR and fluorescent immunostaining for Ki-67 and proliferating cell nuclear antigen (PCNA) in fetal lungs.

Results: CDH fetuses had a lower LBWR than normal fetuses, but comparable pulmonary PCNA and Ki-67 expression levels. TO increased LBWR, irrespective of maternal BM or PLAC. However, BM but not PLAC inhibited proliferation in TO and unoperated fetuses.

Conclusion: Rats with NF-induced CDH have hypoplastic lungs with normal proliferation indices. TO triggers proliferation, an effect countered by BM.