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

Lisa A. Joss-Moore, Yan Wang, Michelle Baack, Jianrong Yao, Andrew W. Norris, Xing Yu, Christopher W. Callaway, Robert A. McKnight, Kurt H. Albertine, Robert H. Lane

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

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. PPAR 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 lung. Because DHA activates PPARγ, we also hypothesized that maternal DHA supplementation would normalize PPARγ, Setd8, and H4K20Me levels in the IUGR rat lung. We found that IUGR decreased PPARγ 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 PPARγ 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 PPARγ, Setd8 and PPARγ 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 PPARγ in the lung and suggests a novel benefit of maternal DHA supplementation in IUGR.

Original languageEnglish (US)
Pages (from-to)785-791
Number of pages7
JournalEarly Human Development
Volume86
Issue number12
DOIs
StatePublished - Dec 1 2010

Fingerprint

Peroxisome Proliferator-Activated Receptors
Mothers
Lung
Acids
Growth
Histone Code
Human Development
Epigenomics
Chromatin
Transcription Factors
Maintenance

Keywords

  • DHA
  • Epigenetics
  • Intrauterine growth restriction
  • Lung development
  • Nuclear receptor
  • PPARgamma
  • Setd8

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Obstetrics and Gynecology

Cite this

IUGR decreases PPARγ and SETD8 Expression in neonatal rat lung and these effects are ameliorated by maternal DHA supplementation. / Joss-Moore, Lisa A.; Wang, Yan; Baack, Michelle; Yao, Jianrong; Norris, Andrew W.; Yu, Xing; Callaway, Christopher W.; McKnight, Robert A.; Albertine, Kurt H.; Lane, Robert H.

In: Early Human Development, Vol. 86, No. 12, 01.12.2010, p. 785-791.

Research output: Contribution to journalArticle

Joss-Moore, LA, Wang, Y, Baack, M, Yao, J, Norris, AW, Yu, X, Callaway, CW, McKnight, RA, Albertine, KH & Lane, RH 2010, 'IUGR decreases PPARγ and SETD8 Expression in neonatal rat lung and these effects are ameliorated by maternal DHA supplementation', Early Human Development, vol. 86, no. 12, pp. 785-791. https://doi.org/10.1016/j.earlhumdev.2010.08.026
Joss-Moore, Lisa A. ; Wang, Yan ; Baack, Michelle ; Yao, Jianrong ; Norris, Andrew W. ; Yu, Xing ; Callaway, Christopher W. ; McKnight, Robert A. ; Albertine, Kurt H. ; Lane, Robert H. / IUGR decreases PPARγ and SETD8 Expression in neonatal rat lung and these effects are ameliorated by maternal DHA supplementation. In: Early Human Development. 2010 ; Vol. 86, No. 12. pp. 785-791.
@article{50dc845e637141aba63955fe84acc3a3,
title = "IUGR decreases PPARγ 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 PPARγ, is thought to contribute to lung development. PPAR 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 lung. Because DHA activates PPARγ, we also hypothesized that maternal DHA supplementation would normalize PPARγ, Setd8, and H4K20Me levels in the IUGR rat lung. We found that IUGR decreased PPARγ 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 PPARγ 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 PPARγ, Setd8 and PPARγ 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 PPARγ in the lung and suggests a novel benefit of maternal DHA supplementation in IUGR.",
keywords = "DHA, Epigenetics, Intrauterine growth restriction, Lung development, Nuclear receptor, PPARgamma, Setd8",
author = "Joss-Moore, {Lisa A.} and Yan Wang and Michelle Baack and Jianrong Yao and Norris, {Andrew W.} and Xing Yu and Callaway, {Christopher W.} and McKnight, {Robert A.} and Albertine, {Kurt H.} and Lane, {Robert H.}",
year = "2010",
month = "12",
day = "1",
doi = "10.1016/j.earlhumdev.2010.08.026",
language = "English (US)",
volume = "86",
pages = "785--791",
journal = "Early Human Development",
issn = "0378-3782",
publisher = "Elsevier Ireland Ltd",
number = "12",

}

TY - JOUR

T1 - IUGR decreases PPARγ and SETD8 Expression in neonatal rat lung and these effects are ameliorated by maternal DHA supplementation

AU - Joss-Moore, Lisa A.

AU - Wang, Yan

AU - Baack, Michelle

AU - Yao, Jianrong

AU - Norris, Andrew W.

AU - Yu, Xing

AU - Callaway, Christopher W.

AU - McKnight, Robert A.

AU - Albertine, Kurt H.

AU - Lane, Robert H.

PY - 2010/12/1

Y1 - 2010/12/1

N2 - 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. PPAR 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 lung. Because DHA activates PPARγ, we also hypothesized that maternal DHA supplementation would normalize PPARγ, Setd8, and H4K20Me levels in the IUGR rat lung. We found that IUGR decreased PPARγ 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 PPARγ 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 PPARγ, Setd8 and PPARγ 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 PPARγ in the lung and suggests a novel benefit of maternal DHA supplementation in IUGR.

AB - 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. PPAR 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 lung. Because DHA activates PPARγ, we also hypothesized that maternal DHA supplementation would normalize PPARγ, Setd8, and H4K20Me levels in the IUGR rat lung. We found that IUGR decreased PPARγ 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 PPARγ 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 PPARγ, Setd8 and PPARγ 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 PPARγ in the lung and suggests a novel benefit of maternal DHA supplementation in IUGR.

KW - DHA

KW - Epigenetics

KW - Intrauterine growth restriction

KW - Lung development

KW - Nuclear receptor

KW - PPARgamma

KW - Setd8

UR - http://www.scopus.com/inward/record.url?scp=78649704656&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78649704656&partnerID=8YFLogxK

U2 - 10.1016/j.earlhumdev.2010.08.026

DO - 10.1016/j.earlhumdev.2010.08.026

M3 - Article

VL - 86

SP - 785

EP - 791

JO - Early Human Development

JF - Early Human Development

SN - 0378-3782

IS - 12

ER -