Camille M Fung1, Yueqin Yang2, Qi Fu3, Ashley S Brown1, Baifeng Yu1, Christopher W Callaway1, Jicheng Li4, Robert H Lane3, Robert A McKnight1. 1. Division of Neonatology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah. 2. 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. 3. Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin. 4. Institute of Cell Biology, Zhejiang University, Hangzhou, Zhejiang, China.
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. 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.
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.
Authors: Rosa Karlić; Ho-Ryun Chung; Julia Lasserre; Kristian Vlahovicek; Martin Vingron Journal: Proc Natl Acad Sci U S A Date: 2010-02-01 Impact factor: 11.205
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Authors: Karen J Gibbins; Katherine N Gibson-Corley; Ashley S Brown; Matthew Wieben; Richard C Law; Camille M Fung Journal: Biol Reprod Date: 2018-05-01 Impact factor: 4.285
Authors: Robert A McKnight; Christian C Yost; Xing Yu; Julia E Wiedmeier; Christopher W Callaway; Ashley S Brown; Robert H Lane; Camille M Fung Journal: Physiol Genomics Date: 2015-10-20 Impact factor: 4.297