IUGR decreases PPARγ and SETD8 Expression in neonatal rat lung and these effects are ameliorated by maternal DHA supplementation

Intrauterine growth restriction (IUGR) is associated with altered lung development in human and rat. The transcription factor PPAR gamma, is thought to contribute to lung development. PPAR gamma is activated by docosahexanoic acid (DNA). One contribution of PPAR gamma to lung development may be its direct regulation of chromatin modifying enzymes, such as Setd8. In this study, we hypothesized that IUGR would result in a gender-specific reduction in PPAR gamma, Setd8 and associated H4K20Me levels in the neonatal rat lung. Because DNA activates PPAR gamma, we also hypothesized that maternal DNA supplementation would normalize PPAR gamma. Setd8, and H4K20Me levels in the IUGR rat lung. We found that IUGR decreased PPAR gamma levels, with an associated decrease in Setd8 levels in both male and female rat lungs. Levels of the Setd8-dependent histone modification, H4K20Me, were reduced on the PPAR gamma gene in both males and females while whole lung H4K20Me was only reduced in male lung. Maternal DNA supplementation ameliorated these effects in offspring. We conclude that IUGR decreases lung PPAR gamma, Setd8 and PPAR gamma H4K20Me independent of gender. while decreasing whole lung H4K20Me in males only. These outcomes are offset by maternal DNA. We speculate that maintenance of the epigenetic milieu may be one role of PPAR gamma in the lung and suggests a novel benefit of maternal DNA supplementation in IUGR. (C) 2010 Elsevier Ireland Ltd. All rights reserved.