Fat dads must not be blamed for their children's health problems

BMC Medicine

Philip Stanier¹  Gudrun E Moore² 

[1] Neural Development Unit, UCL Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK;Clinical and Molecular Genetics Unit, UCL Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK

关键词: genomic imprinting;    DNA methylation;    paternal obesity;    Insulin-like growth factor 2;   

Others  :  857202
DOI  :  10.1186/1741-7015-11-30

 received in 2013-01-29, accepted in 2013-02-06,  发布年份 2013

【 摘 要 】

The relationship between the parental genomes in terms of the future growth and development of their offspring is not critical. For the majority of the genome the tissue-specific gene expression and epigenetic status is shared between the parents equally, with both alleles contributing without parental bias. For a very small number of genes the rules change and control of expression is restricted to a specific, parentally derived allele, a phenomenon known as genomic imprinting. The insulin-like growth factor 2 (Igf2/IGF2) is a robustly imprinted gene, important for fetal growth in both mice and humans. In utero IGF2 exhibits paternal expression, which is controlled by several mechanisms, including the maternally expressing untranslated H19 gene. In the study by Soubry et al., a correlation is drawn between the IGF2 methylation status in fetal cord blood leucocytes, and the obesity status of the father from whom the active IGF2 allele is derived through his sperm. These data imply that paternal obesity affects the normal IGF2 methylation in the sperm and this in turn alters the expression of IGF2 in the baby.

【 授权许可】

   
2013 Moore and Stanier; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Moore T, Haig D: Genomic imprinting in mammalian development: a parental tug-of-war. Trends Genet 1991, 7:45-49.
• [2]DeChiara TM, Robertson EJ, Efstratiadis A: Parental imprinting of the mouse insulin-like growth factor II gene. Cell 1991, 64:849-859.
• [3]DeChiara TM, Efstratiadis A, Robertson EJ: A growth-deficiency phenotype in heterozygous mice carrying an insulin-like growth factor II gene disrupted by targeting. Nature 1990, 345:78-80.
• [4]Wang Z, Fung MR, Barlow DP, Wagner EF: Regulation of embryonic growth and lysosomal targeting by the imprinted Igf2/Mpr gene. Nature 1994, 372:464-467.
• [5]Giannoukakis N, Deal C, Paquette J, Goodyer CG, Polychronakos C: Parental genomic imprinting of the human IGF2 gene. Nat Genet 1993, 4:98-101.
• [6]Rachmilewitz J, Goshen R, Ariel I, Schneider T, de Groot N, Hochberg A: Parental imprinting of the human H19 gene. FEBS Lett 1992, 309:25-28.
• [7]Ishida M, Moore GE: The role of Imprinted genes in humans. Mol Aspects Med 2012, in press.
• [8]Cedar H, Bergman Y: Linking DNA methylation and histone modification: patterns and paradigms. Nat Rev Genet 2009, 10:295-304.
• [9]Hogg K, Price EM, Hanna CW, Robinson WP: Prenatal and perinatal environmental influences on the human fetal and placental epigenome. Clin Pharmacol Ther 2012, 92:716-726.
• [10]Apostolidou S, Abu-Amero S, O'Donoghue K, Frost J, Olafsdottir O, Chavele KM, Whittaker JC, Loughna P, Stanier P, Moore GE: Elevated placental expression of the imprinted PHLDA2 gene is associated with low birth weight. J Mol Med (Berl) 2007, 85:379-387.
• [11]Abu-Amero SN, Ali Z, Bennett P, Vaughan JI, Moore GE: Expression of the insulin-like growth factors and their receptors in term placentas: a comparison between normal and IUGR births. Mol Reprod Dev 1998, 49:229-235.
• [12]Koukoura O, Sifakis S, Soufla G, Zaravinos A, Apostilidou S, Jones A, Widschwendter M, Spandidos DA: Loss of imprinting and aberrant methylation of IGF2 in placentas from pregnancies complicated with fetal growth restriction. Int J Mol Med 2011, 28:481-487.
• [13]Klauwer D, Blum WF, Hanitsch S, Rasher W, Lee PD, Kiess W: IGF-I, IGF-II, free IGF-I and IGFBP-1, -2 and -3 levels in venous cord blood: relationship to birthweight, length and gestational age in healthy newborns. Acta Paediatr 1997, 86:826-833.
• [14]Soubry A, Schildkraut JM, Murtha A, Wang F, Huang Z, Bernal A, Kurtzberg J, Jirtle RL, Murphy SK, Hoyo C: Paternal obesity is associated with IGF2 hypomethylation in newborns: results from a Newborn Epigenetics Study (NEST) cohort. BMC Med 2013, 11:XXXX.
• [15]Hoyo C, Fortner K, Murtha AP, Schildkraut JM, Soubry A, Demark-Wahnefried W, Jirtle RL, Kurtzberg J, Forman MR, Overcash F, Huang Z, Murphy SK: Association of cord blood methylation fractions at imprinted insulin-like growth factor 2 (IGF2), plasma IGF2, and birth weight. Cancer Causes Control 2012, 23:635-645.
• [16]Heijmans BT, Tobi EW, Stein AD, Putter H, Blauw GJ, Susser ES, Slagboom PE, Lumey LH: Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci USA 2008, 105:17046-17049.