Skip to main content Accessibility help

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

  • M. R. Marshall (a1), N. Paneth (a2), J. A. Gerlach (a3), L. M. Mudd (a4), L. Biery (a2), D. P. Ferguson (a5) and J. M. Pivarnik (a2) (a5)...


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.


Corresponding author

Author for correspondence: M. R. Marshall, Department of Kinesiology, Samford University, 800 Lakeshore Dr., Birmingham, AL 35229, USA. E-mail


Hide All
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.
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.
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.
4. Barker, DJ, Winter, PD, Osmond, C, Margetts, B, Simmonds, SJ. Weight in infancy and death from ischaemic heart disease. Lancet. 1989; 2, 577580.
5. Barker, DJ. Adult consequences of fetal growth restriction. Clin Obstet Gynecol. 2006; 49, 270283.
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.
7. Donovan, EL, Miller, BF. Exercise during pregnancy: developmental origins of disease prevention? Exerc Sport Sci Rev. 2011; 39, 111.
8. Chalk, TE, Brown, WM. Exercise epigenetics and the fetal origins of disease. Epigenomics. 2014; 6, 469.
9. Alegría-Torres, JA, Baccarelli, A, Bollati, V. Epigenetics and lifestyle. Epigenomics. 2011; 3, 267277.
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.
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.
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.
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.
14. Liang, H, Ward, WF. PGC-1α: a key regulator of energy metabolism. Adv Physiol Educ. 2006; 30, 145151.
15. Semple, RK, Chatterjee, VKK, O’Rahilly, S. PPARγ and human metabolic disease. J Clin Invest. 2006; 116, 581589.
16. Barres, R, Yan, J, Egan, B, et al. Acute exercise remodels promoter methylation in human skeletal muscle. Cell Metab. 2012; 15, 405411.
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.
18. Leamy, LJ, Pomp, D, Lightfoot, JT. An epistatic genetic basis for physical activity traits in mice. J Hered. 2008; 99, 639646.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
30. Haggarty, P, Hoad, G, Horgan, GW, Campbell, DM. DNA methyltransferase candidate polymorphisms, imprinting methylation, and birth outcome. PLoS One. 2013; 8, e68896.
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.
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.
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.
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.
35. Clapp, JF, Capeless, EL. Neonatal morphometrics after endurance exercise during pregnancy. Am J Obstet Gynecol. 1990; 163, 18051811.
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.
37. Perkins, CC, Pivarnik, JM, Paneth, N, Stein, AD. Physical activity and fetal growth during pregnancy. Obstet Gynecol. 2007; 109, 8187.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.



Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed