Presentation description

The lung disease bronchopulmonary dysplasia (BPD) is common in preterm neonates. The preterm lung is under-developed at birth with the saccular-alveolar transition occurring postnatally rather than in utero. In neonates suffering from BPD, the lung developmental transition is impaired. Normal lung development requires an appropriate level of docosahexaenoic acid (DHA), and its precursor docosapentaenoic acid (DPA). However, clinical trials of DHA supplementation suggest that DHA has negative implications on the developing lung. DHA activates PPARγ, a transcription factor that drives lung development. However, DHA also increases expression of a dominant-negative PPARγ splice variant PPARγΔ5. We hypothesize that the saccular-alveolar transition is characterized by reduced lung levels of DHA and DPA, and that DHA supplementation during the saccular stage increases the portion PPARγ expressed as PPARγΔ5 (PPARγ/PPARγΔ5) in the rat lung. To determine normal rat lung lipid profiles, DHA and DPA were measured before and after the saccular-alveolar transition (mass spectrometry). To determine PPARγ mRNA variant expression with DHA supplementation, PPARγ/PPARγΔ5 was measured in rat lung during the saccular stage (real-time qualitative PCR). Differences were assessed by one-way ANOVA and Fisher's post hoc test. In control rat lung, levels of DHA and DPA decrease with the saccular-alveolar transition (DHA-61±5%, DPA-88±7%). In utero DHA supplementation during the saccular stage increases lung PPARγ/PPARγΔ5 (147±14%). We conclude that, in the rat lung, the saccular-alveolar transition is characterized by reduced DHA and DPA, and that DHA supplementation during the saccular stage increases the expression of the dominant-negative PPARγ variant, PPARγΔ5, potentially impairing lung development.