Hostname: page-component-cd9895bd7-hc48f Total loading time: 0 Render date: 2024-12-27T19:13:03.734Z Has data issue: false hasContentIssue false

Differential methylation of insulin-like growth factor 2 in offspring of physically active pregnant women

Published online by Cambridge University Press:  09 January 2018

M. R. Marshall*
Affiliation:
Department of Kinesiology, Samford University, Birmingham, AL, USA
N. Paneth
Affiliation:
Department of Epidemiology & Biostatistics, Michigan State University, East Lansing, MI, USA
J. A. Gerlach
Affiliation:
Biomedical Laboratory Diagnostics Program, Michigan State University, East Lansing, MI, USA
L. M. Mudd
Affiliation:
National Institutes of Health, National Center for Complementary and Integrative Health, Bethesda, MD, USA
L. Biery
Affiliation:
Department of Epidemiology & Biostatistics, Michigan State University, East Lansing, MI, USA
D. P. Ferguson
Affiliation:
Department of Kinesiology, Michigan State University, East Lansing, MI, USA
J. M. Pivarnik
Affiliation:
Department of Epidemiology & Biostatistics, Michigan State University, East Lansing, MI, USA Department of Kinesiology, Michigan State University, East Lansing, MI, USA
*
Author for correspondence: M. R. Marshall, Department of Kinesiology, Samford University, 800 Lakeshore Dr., Birmingham, AL 35229, USA. E-mail [email protected]

Abstract

Several studies have suggested that maternal lifestyle during pregnancy may influence long-term health of offspring by altering the offspring epigenome. Whether maternal leisure-time physical activity (LTPA) during pregnancy might have this effect is unknown. The purpose of this study was to determine the relationship between maternal LTPA during pregnancy and offspring DNA methylation. Participants were recruited from the Archive for Research on Child Health study. At enrollment, participants’ demographic information and self-reported LTPA during pregnancy were determined. High active participants (averaged 637.5 min per week of LTPA; n=14) were matched by age and race to low active participants (averaged 59.5 min per week LTPA; n=28). Blood spots were obtained at birth. Pyrosequencing was used to determine methylation levels of long interspersed nucleotide elements (LINE-1) (global methylation) and peroxisome proliferator-activated receptor-gamma (PPARγ), peroxisome proliferator-activated receptor-gamma coactivator (PGC1-α), insulin-like growth factor 2 (IGF2), pyruvate dehydrogenase kinase, isozyme 4 (PDK4) and transcription factor 7-like 2 (TCF7L2). We found no differences between offspring of high active and low active groups for LINE-1 methylation. The only differences in candidate gene methylation between groups were at two CpG sites in the P2 promoter of IGF2; the offspring of low active group had significantly higher DNA methylation (74.70±2.25% methylation for low active v. 72.83±2.85% methylation for high active; P=0.045). Our results suggest no effect of maternal LTPA on offspring global and candidate gene methylation, with the exception of IGF2. IGF2 has been previously associated with regulation of physical activity, suggesting a possible role of maternal LTPA on regulation of offspring physical activity.

Type
Original Article
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2018 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Poston, L, Harthoorn, LF, Van Der Beek, EM. Obesity in pregnancy: implications for the mother and lifelong health of the child. A consensus statement. Pediatr Res. 2011; 69, 175180.Google Scholar
2. Katzmarzyk, PT, Pérusse, L, Malina, RM, et al. Stability of indicators of the metabolic syndrome from childhood and adolescence to young adulthood: the Quebec Family Study. J Clin Epidemiol. 2001; 54, 190195.Google Scholar
3. Van Sluijs, EM, McMinn, AM, Griffin, SJ. Effectiveness of interventions to promote physical activity in children and adolescents: systematic review of controlled trials. BMJ. 2007; 335, 703.Google Scholar
4. Barker, DJ, Winter, PD, Osmond, C, Margetts, B, Simmonds, SJ. Weight in infancy and death from ischaemic heart disease. Lancet. 1989; 2, 577580.CrossRefGoogle ScholarPubMed
5. Barker, DJ. Adult consequences of fetal growth restriction. Clin Obstet Gynecol. 2006; 49, 270283.Google Scholar
6. Heerwagen, MJ, Miller, MR, Barbour, LA, Friedman, JE. Maternal obesity and fetal metabolic programming: a fertile epigenetic soil. Am J Physiol Regul Integr Comp Physiol. 2010; 299, R711R722.Google Scholar
7. Donovan, EL, Miller, BF. Exercise during pregnancy: developmental origins of disease prevention? Exerc Sport Sci Rev. 2011; 39, 111.Google Scholar
8. Chalk, TE, Brown, WM. Exercise epigenetics and the fetal origins of disease. Epigenomics. 2014; 6, 469.Google Scholar
9. Alegría-Torres, JA, Baccarelli, A, Bollati, V. Epigenetics and lifestyle. Epigenomics. 2011; 3, 267277.Google Scholar
10. Huse, SM, Gruppuso, PA, Boekelheide, K, Sanders, JA. Patterns of gene expression and DNA methylation in human fetal and adult liver. BMC Genomics. 2015; 16, 981.Google Scholar
11. Heijmans, BT, Tobi, EW, Stein, AD, et al. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci. 2008; 105, 1704617049.Google Scholar
12. Dominguez-Salas, P, Moore, SE, Baker, MS, et al. Maternal nutrition at conception modulates DNA methylation of human metastable epialleles. Nat Commun. 2014; 5, 3746.Google Scholar
13. Haggarty, P, Hoad, G, Campbell, DM, et al. Folate in pregnancy and imprinted gene and repeat element methylation in the offspring. Am J Clin Nutr. 2013; 97, 9499.Google Scholar
14. Liang, H, Ward, WF. PGC-1α: a key regulator of energy metabolism. Adv Physiol Educ. 2006; 30, 145151.Google Scholar
15. Semple, RK, Chatterjee, VKK, O’Rahilly, S. PPARγ and human metabolic disease. J Clin Invest. 2006; 116, 581589.CrossRefGoogle ScholarPubMed
16. Barres, R, Yan, J, Egan, B, et al. Acute exercise remodels promoter methylation in human skeletal muscle. Cell Metab. 2012; 15, 405411.Google Scholar
17. Constância, M, Hemberger, M, Hughes, J, Dean, W. Placental-specific IGF-II is a major modulator of placental and fetal growth. Nature. 2002; 417, 945948.Google Scholar
18. Leamy, LJ, Pomp, D, Lightfoot, JT. An epistatic genetic basis for physical activity traits in mice. J Hered. 2008; 99, 639646.Google Scholar
19. Simonen, RL, Rankinen, T, Perusse, L, et al. Genome-wide linkage scan for physical activity levels in the Quebec Family study. Med Sci Sports Exerc. 2003; 35, 13551359.CrossRefGoogle ScholarPubMed
20. Grant, SF, Thorleifsson, G, Reynisdottir, I, et al. Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet. 2006; 38, 320323.Google Scholar
21. Morris, J, Pollard, R, Everitt, M, Chave, S, Semmence, A. Vigorous exercise in leisure-time: protection against coronary heart disease. Lancet. 1980; 316, 12071210.Google Scholar
22. King, GA, Fitzhugh, E, Bassett, D Jr, et al. Relationship of leisure-time physical activity and occupational activity to the prevalence of obesity. Int J Obes Relat Metab Disord. 2001; 25, 606612.Google Scholar
23. Adkins, RM, Krushkal, J, Tylavsky, FA, Thomas, F. Racial differences in gene‐specific DNA methylation levels are present at birth. Birth Defects Res A Clin Mol Teratol. 2011; 91, 728736.Google Scholar
24. Adkins, RM, Thomas, F, Tylavsky, FA, Krushkal, J. Parental ages and levels of DNA methylation in the newborn are correlated. BMC Med Genet. 2011; 12, 47.Google Scholar
25. Borghol, N, Suderman, M, McArdle, W, et al. Associations with early-life socio-economic position in adult DNA methylation. Int J Epidemiol. 2011; 41, 6274.Google Scholar
26. El-Maarri, O, Becker, T, Junen, J, et al. Gender specific differences in levels of DNA methylation at selected loci from human total blood: a tendency toward higher methylation levels in males. Hum Genet. 2007; 122, 505514.Google Scholar
27. Gemma, C, Sookoian, S, Alvariñas, J, et al. Maternal pregestational BMI is associated with methylation of the PPARGC1A promoter in newborns. Obesity. 2009; 17, 10321039.CrossRefGoogle ScholarPubMed
28. Michels, KB, Harris, HR, Barault, L. Birthweight, maternal weight trajectories and global DNA methylation of LINE-1 repetitive elements. PLoS One. 2011; 6, e25254.Google Scholar
29. Knopik, VS, Maccani, MA, Francazio, S, McGeary, JE. The epigenetics of maternal cigarette smoking during pregnancy and effects on child development. Deve Psychopathol. 2012; 24, 13771390.Google Scholar
30. Haggarty, P, Hoad, G, Horgan, GW, Campbell, DM. DNA methyltransferase candidate polymorphisms, imprinting methylation, and birth outcome. PLoS One. 2013; 8, e68896.CrossRefGoogle ScholarPubMed
31. White, AJ, Sandler, DP, Bolick, SC, et al. Recreational and household physical activity at different time points and DNA global methylation. Eur J Cancer. 2013; 49, 21992206.Google Scholar
32. Kile, ML, Baccarelli, A, Tarantini, L, et al. Correlation of global and gene-specific DNA methylation in maternal-infant pairs. PloS One. 2010; 5, e13730.Google Scholar
33. Zhang, FF, Cardarelli, R, Carroll, J, et al. Physical activity and global genomic DNA methylation in a cancer-free population. Epigenetics. 2011; 6, 293299.Google Scholar
34. Luttropp, K, Nordfors, L, Ekström, TJ, Lind, L. Physical activity is associated with decreased global DNA methylation in Swedish older individuals. Scand J Clin Lab Invest. 2013; 73, 184185.Google Scholar
35. Clapp, JF, Capeless, EL. Neonatal morphometrics after endurance exercise during pregnancy. Am J Obstet Gynecol. 1990; 163, 18051811.CrossRefGoogle ScholarPubMed
36. Clapp, JF, Kim, H, Burciu, B, et al. Continuing regular exercise during pregnancy: effect of exercise volume on fetoplacental growth. Am J Obstet Gynecol. 2002; 186, 142147.Google Scholar
37. Perkins, CC, Pivarnik, JM, Paneth, N, Stein, AD. Physical activity and fetal growth during pregnancy. Obstet Gynecol. 2007; 109, 8187.CrossRefGoogle ScholarPubMed
38. Hoyo, C, Murtha, AP, Schildkraut, JM, et al. Methylation variation at IGF2 differentially methylated regions and maternal folic acid use before and during pregnancy. Epigenetics. 2011; 6, 928936.CrossRefGoogle ScholarPubMed
39. Cui, H, Cruz-Correa, M, Giardiello, FM, et al. Loss of IGF2 imprinting: a potential marker of colorectal cancer risk. Science. 2003; 299, 17531755.CrossRefGoogle ScholarPubMed
40. Cruz-Correa, M, Cui, H, Giardiello, FM, et al. Loss of imprinting of insulin growth factor II gene: a potential heritable biomarker for colon neoplasia predisposition. Gastroenterology. 2004; 126, 964970.Google Scholar
41. Nehrenberg, DL, Wang, S, Hannon, RM, Garland, T Jr, Pomp, D. QTL underlying voluntary exercise in mice: interactions with the ‘mini muscle’ locus and sex. J Hered. 2009; 101, 4253.Google Scholar
42. Sayer, AA, Syddall, H, O’dell, SD, et al. Polymorphism of the IGF2 gene, birth weight and grip strength in adult men. Age Ageing. 2002; 31, 468470.CrossRefGoogle ScholarPubMed
43. Joubert, BR, Håberg, SE, Bell, DA. et al. Maternal smoking and DNA methylation in newborns: in utero effect or epigenetic inheritance? Cancer Epidemiology, Biomarkers & Prevention: a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2014; 23, 10071017.CrossRefGoogle ScholarPubMed
44. Liu, X, Chen, Q, Tsai, HJ, et al. Maternal preconception body mass index and offspring cord blood DNA methylation: exploration of early life origins of disease. Environ Mol Mutagen. 2014; 55, 223230.CrossRefGoogle ScholarPubMed
45. Hyatt, HW, Toedebusch, RG, Ruegsegger, G, et al. Comparative adaptations in oxidative and glycolytic muscle fibers in a low voluntary wheel running rat model performing three levels of physical activity. Physiol Rep. 2015; 3, e12619.Google Scholar
46. Aagaard-Tillery, KM, Grove, K, Bishop, J, et al. Developmental origins of disease and determinants of chromatin structure: maternal diet modifies the primate fetal epigenome. J Mol Endocrinol. 2008; 41, 91102.Google Scholar
47. Bauer, PW, Pivarnik, JM, Feltz, DL, Paneth, N, Womack, CJ. Validation of an historical physical activity recall tool in postpartum women. J Phys Act Health. 2010; 7, 658661.Google Scholar