IUGR prevents IGF-1 upregulation in juvenile male mice by perturbing postnatal IGF-1 chromatin remodeling. Pediatr Res 2015 Jul;78(1):14-23
Date
04/01/2015Pubmed ID
25826117DOI
10.1038/pr.2015.70Scopus ID
2-s2.0-84931846529 (requires institutional sign-in at Scopus site) 16 CitationsAbstract
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.
CONCLUSION: 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.
Author List
Fung CM, Yang Y, Fu Q, Brown AS, Yu B, Callaway CW, Li J, Lane RH, McKnight RAMESH terms used to index this publication - Major topics in bold
AnimalsBlood Glucose
Body Weight
Chromatin
Chromatin Assembly and Disassembly
DNA Methylation
Exons
Female
Fetal Growth Retardation
Gene Expression Regulation, Developmental
Histones
Insulin
Insulin-Like Growth Factor I
Liver
Male
Mice
Mice, Inbred C57BL
Obesity
Promoter Regions, Genetic
Risk Factors
Sex Factors
Thromboxane A2
