Objectives: 

Lung development is a complex process regulated by several molecular interactions. Anomalies in those induce respiratory pathology associated with lung immaturity and incompatible with extra-uterine life. Glucagon-like peptide (GLP-1) induces pulmonary surfactant phosphatidylcholine. The objective of this study was to analyze the liraglutide ability (Lir, GLP-1 analogue) to stimulate lung development and to improve respiratory function in a lung hypoplasia model.

Materials: 

Pregnant rats were divided in two halves (n=15), one treated with vehicle (1 ml of pure olive oil) and the other group administered with 100 mg of nitrofen (NTF) intragastrically on 9th day of pregnancy (9GD).Afterwards both groups were distributed in 3 experimental branches (n=5) receiving either vehicle, Lir (100μg/kg/12 hr. s.c.) or Dexamethasone (20 μg/kg/day, s.c.). At 21 GD fetuses were removed and weighted (Body Weight, BW). Lungs were dissected and weighted (Lung Weight, LW). LW/BW ratio (mg/g) was determined as indicator of lung development. SP-A and SP-B (proteins of pulmonary surfactant) gene expression and protein levels were determined. Some fetuses were allowed to spontaneously delivery to determinate survival rate after delayed lung development induced by NTF and to analyze the effects of prenatal hormonal therapy.

Results: 

Pattern gene expression of surfactant proteins and their protein levels on lungs showed mRNA and protein levels diminished in NTF-treated respect to control group, however this alterations on surfactant composition were recovered by prenatal treatment with Lir or Dex. Nitrofen administration triggers lung immaturity as shown LW/BW reduction. Lir increased LW/BW on fetuses with incomplete lung development, and increased survival rate of NTF-neonates.

Conclusions: 

As a whole, our data show that antenatal hormone therapy with Lir recovers lung function and surfactant protein deficiency in an incomplete lung development model.