Oral or Poster Presentation
Concurrent Session 1B - Placental Fetal Physiology
Introduction: Respiratory distress syndrome affects about 1% of newborns and is a leading cause of neonatal morbidity and mortality in preterm infants. It results from inadequate functional pulmonary surfactant. Surfactant produced by Type II alveolar epithelial cells (AECs) is essential for reducing surface tension at the air-liquid interface, thus protecting the newborn lung from alveolar collapse. Peroxisome proliferator-activated receptor γ (PPARγ) is an important factor for activation of pulmonary lipofibroblasts to produce leptin, which binds to Type II AECs and stimulates surfactant synthesis. In this study, we examined the effect of intrafetal administration of a PPARγ agonist, rosiglitazone (RGZ), on surfactant maturation in the fetal lung during late gestation.
Methods: Four osmotic mini pumps containing vehicle (VEH, n=8, 15% ethanol) or RGZ (n=7, 4.28mg/fetus/day) were implanted subcutaneously into fetuses at 123-126 d gestation (term, 150 d)1. Fetal lung tissue was collected at 138-42 d for molecular and immunohistochemical analyses. The effect of RGZ on surfactant production was determined using a Student’s unpaired t-test. P < 0.05 was considered statistically significant.
Results: There was no difference in the mRNA expression of PPARγ, surfactant protein (SFTP-A, -B, -C) and -D, PCYT1A (surfactant phospholipid synthesis), ABCA3 (phospholipid transportation) or the PPARγ responsive genes PAI-1, PGC1a, RXRa between VEH and RGZ groups. There was a reduction in mRNA expression of LPCAT1 (surfactant phospholipid synthesis) and LAMP3 (marker for lamellar bodies) and an increase in SPHK1 (PPARγ target gene) expression in RGZ group. There was also an increased mRNA expression of VEGFR1 in RGZ group, which plays both a stimulatory and inhibitory role in pulmonary angiogenesis.
Conclusion: These results indicate a potential decreased capacity for surfactant phospholipid production, despite increased PPARγ activity in other fetal tissues (Figure 1). However, the mRNA expression for the majority of genes involved in surfactant protein production did not change following RGZ treatment.