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

ABSTRACT: Intrauterine growth restriction (IUGR) is associated with altered lung development in human and rat. The transcription factor PPAR?, is thought to contribute to lung development. PPAR? is activated by docosahexanoic acid (DHA). One contribution of PPAR? 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?, Setd8 and associated H4K20Me levels in the neonatal rat lung. Because DHA activates PPAR?, we also hypothesized that maternal DHA supplementation would normalize PPAR?, Setd8, and H4K20Me levels in the IUGR rat lung. We found that IUGR decreased PPAR? 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? gene in both males and females while whole lung H4K20Me was only reduced in male lung. Maternal DHA supplementation ameliorated these effects in offspring. We conclude that IUGR decreases lung PPAR?, Setd8 and PPAR? H4K20Me independent of gender, while decreasing whole lung H4K20Me in males only. These outcomes are offset by maternal DHA. We speculate that maintenance of the epigenetic milieu may be one role of PPAR? in the lung and suggests a novel benefit of maternal DHA supplementation in IUGR.

SUBMITTER: Joss-Moore LA

PROVIDER: S-EPMC3138525 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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

Joss-Moore Lisa A LA Wang Yan Y Baack Michelle L ML Yao Jianrong J Norris Andrew W AW Yu Xing X Callaway Christopher W CW McKnight Robert A RA Albertine Kurt H KH Lane Robert H RH

Early human development 20100924 12

Intrauterine growth restriction (IUGR) is associated with altered lung development in human and rat. The transcription factor PPARγ, is thought to contribute to lung development. PPARγ is activated by docosahexanoic acid (DHA). One contribution of PPARγ 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 PPARγ, Setd8 and associated H4K20Me levels in the neonatal rat ...[more]

PMID: 20869820

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

Publications

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

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