title: IUGR prevents IGF-1 upregulation in juvenile male mice by perturbing postnatal IGF-1 chromatin remodeling.
abstract: BACKGROUND
  Intrauterine growth restriction (IUGR) offspring with rapid catch-up growth are at increased risk for early obesity especially in males. Persistent insulin-like growth factor-1 (IGF-1) reduction is an important risk factor. Using a mouse model of maternal hypertension-induced IUGR, we examined IGF-1 levels, promoter DNA methylation, and histone H3 covalent modifications at birth (D1). We additionally investigated whether prenatal perturbations could reset at preadolescence (D21).
  
  
  METHODS
  IUGR was induced via maternal thromboxane A2-analog infusion in mice.
  
  
  RESULTS
  IUGR uniformly decreased D1 IGF-1 mRNA and protein levels with reduced promoter 1 (P1) transcription and increased P1 DNA methylation. IUGR males also had increased H3K4ac at exon 5 and 3' distal UTR. At D21, IUGR males continued to have decreased IGF-1 levels, originating from both P1 and P2 with reduced 1A variant. IUGR males also had decreased activation mark of H3K4me3 at P1 compared with sham males. In contrast, D21 IUGR females normalized their IGF-1 levels, in association with an increased activation mark of H3K4me3 at P1 compared with sham females.
  
  
  CONCLUSIONS
  IUGR uniformly affected D1 hepatic IGF-1 epigenetic modifications in both sexes. However, at preadolescence, IUGR males are unable to correct for the prenatal reduction possibly due to a more perturbed IGF-1 chromatin structure.
authors.affiliation: Division of Neonatology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah.
authors.forename: Camille M
authors.initials: CM
authors.lastname: Fung
authors.affiliation: 1] Division of Neonatology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah [2] Institute of Cell Biology, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Yueqin
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Qi
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Division of Neonatology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah.
authors.forename: Ashley S
authors.initials: AS
authors.lastname: Brown
authors.affiliation: Division of Neonatology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah.
authors.forename: Baifeng
authors.initials: B
authors.lastname: Yu
authors.affiliation: Division of Neonatology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Callaway
authors.affiliation: Institute of Cell Biology, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Jicheng
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Lane
authors.affiliation: Division of Neonatology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah.
authors.forename: Robert A
authors.initials: RA
authors.lastname: McKnight
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D002843:Chromatin / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D019175:DNA Methylation; D005091:Exons; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006657:Histones / Q000737:chemistry; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D012737:Sex Factors; D013928:Thromboxane A2 / Q000737:chemistry
chemical_list: D001786:Blood Glucose; D002843:Chromatin; D006657:Histones; D007328:Insulin; C519530:insulin-like growth factor-1, mouse; D013928:Thromboxane A2; D007334:Insulin-Like Growth Factor I
references.citation: Proc Nutr Soc. 2007 Aug;66(3):451-7
references.pmid: 17637098
references.citation: Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):2926-31
references.pmid: 20133639
references.citation: Physiol Genomics. 2004 Jun 17;18(1):43-50
references.pmid: 15084713
references.citation: Int J Obes Relat Metab Disord. 2004 Nov;28 Suppl 3:S46-53
references.pmid: 15543219
references.citation: FASEB J. 2009 Aug;23(8):2438-49
references.pmid: 19364764
references.citation: Front Biosci. 2007 Jan 01;12:2457-70
references.pmid: 17127255
references.citation: N Engl J Med. 1997 Feb 27;336(9):633-40
references.pmid: 9032050
references.citation: Oncogene. 2008 Apr 10;27(17):2412-21
references.pmid: 17968314
references.citation: Am J Physiol Heart Circ Physiol. 2005 Aug;289(2):H674-82
references.pmid: 15833805
references.citation: Pediatr Res. 2003 Jul;54(1):83-90
references.pmid: 12646717
references.citation: Biochem Cell Biol. 2007 Aug;85(4):435-43
references.pmid: 17713579
references.citation: J Physiol Pharmacol. 2009 Oct;60 Suppl 3:17-35
references.pmid: 19996479
references.citation: Nucleic Acids Res. 2014 Jan;42(2):701-13
references.pmid: 24081581
references.citation: Cell Rep. 2012 Jul 26;2(1):62-8
references.pmid: 22840397
references.citation: Proc Natl Acad Sci U S A. 1987 Dec;84(24):8946-50
references.pmid: 3480521
references.citation: Mol Pharmacol. 2009 Aug;76(2):215-28
references.pmid: 19483103
references.citation: Biochim Biophys Acta. 2014 Dec;1839(12):1353-61
references.pmid: 24631869
references.citation: Am J Physiol Regul Integr Comp Physiol. 2003 Nov;285(5):R962-70
references.pmid: 12869365
references.citation: Nat Struct Mol Biol. 2011 Mar;18(3):337-44
references.pmid: 21358630
references.citation: Pediatr Res. 2013 Apr;73(4 Pt 2):531-42
references.pmid: 23314294
references.citation: J Dev Orig Health Dis. 2011 Oct;2(5):291-301
references.pmid: 25141265
references.citation: Am J Physiol Regul Integr Comp Physiol. 2011 Sep;301(3):R561-71
references.pmid: 21677270
references.citation: Horm Res. 2003;60 Suppl 3:115-23
references.pmid: 14671408
references.citation: Nat Clin Pract Endocrinol Metab. 2007 Mar;3(3):302-10
references.pmid: 17315038
references.citation: J Biol Chem. 1992 Oct 25;267(30):21505-11
references.pmid: 1400462
references.citation: J Neuroendocrinol. 2009 Mar;21(4):377-86
references.pmid: 19207816
references.citation: J Biol Chem. 1978 Apr 25;253(8):2769-76
references.pmid: 632300
references.citation: J Biol Chem. 2006 Feb 10;281(6):3190-7
references.pmid: 16339156
references.citation: Metab Syndr Relat Disord. 2012 Feb;10(1):3-13
references.pmid: 22103319
references.citation: Development. 2011 Feb;138(4):777-86
references.pmid: 21266413
references.citation: Reproduction. 2003 Jun;125(6):785-90
references.pmid: 12773100
references.citation: Nature. 2007 Aug 9;448(7154):718-22
references.pmid: 17687328
references.citation: Semin Perinatol. 2010 Jun;34(3):207-10
references.pmid: 20494737
references.citation: Endocr Relat Cancer. 2012 Sep 05;19(5):F27-45
references.pmid: 22593429
references.citation: Nat Rev Neurosci. 2004 Sep;5(9):701-8
references.pmid: 15322528
references.citation: Appl Physiol Nutr Metab. 2006 Dec;31(6):791-7
references.pmid: 17213901