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Associations between maternal prenatal stress, methylation changes in IGF1 and IGF2, and birth weight

Published online by Cambridge University Press:  11 October 2017

D. Montoya-Williams Open the ORCID record for D. Montoya-Williams [Opens in a new window] ,
J. Quinlan ,
C. Clukay ,
N. C. Rodney ,
D. A. Kertes  and
C. J. Mulligan
D. Montoya-Williams*
Affiliation:
Department of Pediatrics, University of Florida, Gainesville, FL, USA
J. Quinlan
Affiliation:
Department of Anthropology, University of Florida, Gainesville, FL, USA Genetics Institute, University of Florida, Gainesville, FL, USA
C. Clukay
Affiliation:
Department of Anthropology, University of Florida, Gainesville, FL, USA Genetics Institute, University of Florida, Gainesville, FL, USA
N. C. Rodney
Affiliation:
Department of Anthropology, University of Florida, Gainesville, FL, USA
D. A. Kertes
Affiliation:
Genetics Institute, University of Florida, Gainesville, FL, USA Department of Psychology, University of Florida, Gainesville, FL, USA
C. J. Mulligan
Affiliation:
Department of Anthropology, University of Florida, Gainesville, FL, USA Genetics Institute, University of Florida, Gainesville, FL, USA
*
*Address for correspondence: D. Montoya-Williams, Division of Neonatology, UF Health Shands Hospital, PO Box 100296, Gainesville, FL 32610, USA. (Email [email protected])
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Abstract

Maternal stress has been linked to low birth weight in newborns. One potential pathway involves epigenetic changes at candidate genes that may mediate the effects of prenatal maternal stress on birth weight. This relationship has been documented in stress-related genes, such as NR3C1. There is less literature exploring the effect of stress on growth-related genes. IGF1 and IGF2 have been implicated in fetal growth and development, though via different mechanisms as IGF2 is under imprinting control. In this study, we tested for associations between prenatal stress, methylation of IGF1 and IGF2, and birth weight. A total of 24 mother–newborn dyads in the Democratic Republic of Congo were enrolled. Ethnographic interviews were conducted with mothers at delivery to gather culturally relevant war-related and chronic stressors. DNA methylation data were generated from maternal venous, cord blood and placental tissue samples. Multivariate regressions were used to test for associations between stress measures, DNA methylation and birth weight in each of the three tissue types. We found an association between IGF2 methylation in maternal blood and birth weight. Previous literature on the relationship between IGF2 methylation and birth weight has focused on methylation at known differentially methylated regions in cord blood or placental samples. Our findings indicate there may be links between the maternal epigenome and low birth weight that rely on mechanisms outside known imprinting pathways. It thus may be important to consider the effect of maternal exposures and epigenetic profiles on birth weight even in the setting of maternally imprinted genes such as IGF2.

Keywords

birth weightIGF2methylationprenatal stress
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 9 , Issue 2 , April 2018 , pp. 215 - 222
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Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2017 

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References

1. Risnes, KR, Vatten, LJ, Baker, JL, et al. Birthweight and mortality in adulthood: a systematic review and meta-analysis. Int J Epidemiol. 2011; 40, 647–661.Google Scholar
2. Raju, TNK, Buist, AS, Blaisdell, CJ, Moxey-Mims, M, Saigal, S. Adults born preterm: a review of general health and system-specific outcomes. Acta Paediatr. 2017; 106, 1409–1437.Google Scholar
3. Lee, AC, Kozuki, N, Cousens, S, et al. Estimates of burden and consequences of infants born small for gestational age in low and middle income countries with INTERGROWTH-21(st) standard: analysis of CHERG datasets. BMJ. 2017; 358, j3677.CrossRefGoogle ScholarPubMed
4. Kramer, MS. Determinants of low birth weight: methodological assessment and meta-analysis. Bull World Health Organ. 1987; 65, 663–737.Google ScholarPubMed
5. Burris, HH, Hacker, MR. Birth outcome racial disparities: a result of intersecting social and environmental factors. Semin Perinatol. 2017; 1–7 (in press). https://doi.org/10.1053/j.semperi.2017.07.002 Google Scholar
6. Lu, MC, Halfon, N. Racial and ethnic disparities in birth outcomes: a life-course perspective. Matern Child Health J. 2003; 7, 13–30.CrossRefGoogle ScholarPubMed
7. Kertes, DA, Kamin, HS, Hughes, DA, et al. Prenatal maternal stress predicts methylation of genes regulating the hypothalamic-pituitary-adrenocortical system in mothers and newborns in the Democratic Republic of Congo. Child Dev. 2016; 87, 61–72.Google Scholar
8. Vidal, AC, Benjamin Neelon, SE, Liu, Y, et al. Maternal stress, preterm birth, and DNA methylation at imprint regulatory sequences in humans. Genet Epigenet. 2014; 6, 37–44.Google Scholar
9. Class, QA, Lichtenstein, P, Långström, N, D’Onofrio, BM. Timing of prenatal maternal exposure to severe life events and adverse pregnancy outcomes: a population study of 2.6 million pregnancies. Psychosom Med. 2011; 73, 234–241.Google Scholar
10. Duthie, L, Reynolds, RM. Changes in the maternal hypothalamic-pituitary-adrenal axis in pregnancy and postpartum: influences on maternal and fetal outcomes. Neuroendocrinology. 2013; 98, 106–115.CrossRefGoogle ScholarPubMed
11. Hobel, CJ, Goldstein, A, Barrett, ES. Psychosocial stress and pregnancy outcome. Clin Obstet Gynecol. 2008; 51, 333–348.CrossRefGoogle ScholarPubMed
12. Hanson, MA, Gluckman, PD. Developmental origins of health and disease: new insights. Basic Clin Pharmacol Toxicol. 2008; 102, 90–93.Google Scholar
13. Barker, DJP, Thornburg, KL. The obstetric origins of health for a lifetime. Clin Obstet Gynecol. 2013; 56, 511–519.CrossRefGoogle ScholarPubMed
14. Thayer, ZM, Kuzawa, CW. Biological memories of past environments: epigenetic pathways to health disparities. Epigenetics. 2011; 6, 798–803.Google Scholar
15. Barouki, R, Gluckman, PD, Grandjean, P, Hanson, M, Heindel, JJ. Developmental origins of non-communicable disease: implications for research and public health. Environ Health. 2012; 11, 42.Google Scholar
16. Cao-Lei, L, Dancause, KN, Elgbeili, G, et al. DNA methylation mediates the impact of exposure to prenatal maternal stress on BMI and central adiposity in children at age 13 1/2 years: Project Ice Storm. Epigenetics. 2015; 10, 749–761.Google Scholar
17. King, K, Murphy, S, Hoyo, C. Epigenetic regulation of newborns’ imprinted genes related to gestational growth: patterning by parental race/ethnicity and maternal socioeconomic status. J Epidemiol Community Health. 2015; 69, 639–647.CrossRefGoogle Scholar
18. Cunliffe, VT. The epigenetic impacts of social stress: how does social adversity become biologically embedded? Epigenomics. 2016; 8, 1653–1669.Google Scholar
19. Mulligan, CJ, D’Errico, NC, Stees, J, Hughes, DA. Methylation changes at NR3C1 in newborns associate with maternal prenatal stress exposure and newborn birth weight. Epigenetics. 2012; 7, 853–857.Google Scholar
20. Agis-Balboa, RC, Fischer, A. Generating new neurons to circumvent your fears: the role of IGF signaling. Cell Mol Life Sci. 2014; 71, 21–42.Google Scholar
21. Hiden, U, Glitzner, E, Hartmann, M, Desoye, G. Insulin and the IGF system in the human placenta of normal and diabetic pregnancies. J Anat. 2009; 215, 60–68.Google Scholar
22. Mansell, T, Novakovic, B, Meyer, B, et al. The effects of maternal anxiety during pregnancy on IGF2/H19 methylation in cord blood. Transl Psychiatry. 2016; 6, e765.CrossRefGoogle ScholarPubMed
23. Johnston, LB, Dahlgren, J, Leger, J, et al. Association between insulin-like growth factor I (IGF-I) polymorphisms, circulating IGF-I, and pre- and postnatal growth in two European small for gestational age populations. J Clin Endocrinol Metab. 2003; 88, 4805–4810.Google Scholar
24. Adkins, RM, Somes, G, Morrison, JC, et al. Association of birth weight with polymorphisms in the IGF2, H19, and IGF2R genes. Pediatr Res. 2010; 68, 429–434.Google Scholar
25. Kadakia, R, Ma, M, Josefson, JL. Neonatal adiposity increases with rising cord blood IGF-1 levels. Clin Endocrinol (Oxf). 2016; 85, 70–75.CrossRefGoogle ScholarPubMed
26. Zhang, S, Zhai, G, Wang, J, et al. IGF-II expression and methylation in small for gestational age infants. J Pediatr Endocrinol Metab. 2015; 28, 613–618.Google Scholar
27. Boucher, J, Charalambous, M, Zarse, K, et al. Insulin and insulin-like growth factor 1 receptors are required for normal expression of imprinted genes. Proc Natl Acad Sci USA. 2014; 111, 14512–14517.Google Scholar
28. Le, F, Wang, LY, Wang, N, et al. In vitro fertilization alters growth and expression of Igf2/H19 and their epigenetic mechanisms in the liver and skeletal muscle of newborn and elder mice. Biol Reprod. 2013; 88, 75.Google Scholar
29. Begemann, M, Zirn, B, Santen, G, et al. Paternally inherited IGF2 mutation and growth restriction. N Engl J Med. 2015; 373, 349–356.CrossRefGoogle ScholarPubMed
30. Chao, W, D’Amore, PA. IGF2: epigenetic regulation and role in development and disease. Cytokine Growth Factor Rev. 2008; 19, 111–120.Google Scholar
31. Ouni, M, Gunes, Y, Belot, M-P, et al. The IGF1 P2 promoter is an epigenetic QTL for circulating IGF1 and human growth. Clin Epigenetics. 2015; 7, 22.Google Scholar
32. Straughen, JK, Sipahi, L, Uddin, M, Misra, DP, Misra, VK. Racial differences in IGF1 methylation and birth weight. Clin Epigenetics. 2015; 7, 47.Google Scholar
33. Bouwland-Both, MI, van Mil, NH, Stolk, L, et al. DNA methylation of IGF2DMR and H19 is associated with fetal and infant growth: the generation R study. PLoS One. 2013; 8, e81731.CrossRefGoogle ScholarPubMed
34. St-Pierre, J, Hivert, M, Perron, P, et al. IGF2 DNA methylation is a modulator of newborn’s fetal growth and development. Epigenetics. 2012; 7, 1125–1132.Google Scholar
35. Toure, DM, Baccaglini, L, Opoku, ST, et al. Epigenetic dysregulation of Insulin-like growth factor (IGF)-related genes and adverse pregnancy outcomes: a systematic review. J Matern Fetal Neonatal Med. 2016; 29, 1–11.Google Scholar
36. Mina, TH, Räikkönen, K, Riley, SC, Norman, JE, Reynolds, RM. Maternal distress associates with placental genes regulating fetal glucocorticoid exposure and IGF2: Role of obesity and sex. Psychoneuroendocrinology. 2015; 59, 112–122.Google Scholar
37. Vangeel, EB, Izzi, B, Hompes, T, et al. DNA methylation in imprinted genes IGF2 and GNASXL is associated with prenatal maternal stress. Genes Brain Behav. 2015; 61, 16.Google Scholar
38. Liu, Y, Murphy, SK, Murtha, AP, et al. Depression in pregnancy, infant birth weight and DNA methylation of imprint regulatory elements. Epigenetics. 2012; 7, 735–746.CrossRefGoogle ScholarPubMed
39. Heijmans, BT, Tobi, EW, Stein, AD, et al. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci USA. 2008; 105, 17046–17049.Google Scholar
40. Rodney, NC, Mulligan, CJ. A biocultural study of the effects of maternal stress on mother and newborn health in the Democratic Republic of Congo. Am J Phys Anthropol. 2014; 209, 200–209.Google Scholar
41. Barfield, RT, Almli, LM, Kilaru, V, et al. Accounting for population stratification in DNA methylation studies. Genet Epidemiol. 2014; 38, 231–241.Google Scholar
42. Rahmani, E, Zaitlen, N, Baran, Y, et al. Sparse PCA corrects for cell type heterogeneity in epigenome-wide association studies. Nat Methods. 2016; 13, 443–445.Google Scholar
43. Houseman, EA, Accomando, WP, Koestler, DC, et al. DNA methylation arrays as surrogate measures of cell mixture distribution. BMC Bioinformatics. 2012; 13, 86.CrossRefGoogle ScholarPubMed
44. Aryee, MJ, Jaffe, AE, Corrada-Bravo, H, et al. Minfi: a flexible and comprehensive bioconductor package for the analysis of infinium DNA methylation microarrays. Bioinformatics. 2014; 30, 1363–1369.Google Scholar
45. Bakulski, KM, Feinberg, JI, Andrews, S V, et al. DNA methylation of cord blood cell types: applications for mixed cell birth studies. Epigenetics. 2016; 11, 354–362.Google Scholar
46. Restrepo-Méndez, MC, Lawlor, DA, Horta, BL, et al. The association of maternal age with birthweight and gestational age: a cross-cohort comparison. Paediatr Perinat Epidemiol. 2015; 29, 31–40.Google Scholar
47. Muula, AS, Siziya, S, Rudatsikira, E. Parity and maternal education are associated with low birth weight in Malawi. Afr Health Sci. 2011; 11, 65–71.Google Scholar
48. SAS Institute Inc. Jmp® genomics, 7.0 ed, 2013. SAS Institute Inc.: Cary, NC, USA.Google Scholar
49. R Core Team. R: A language and environment for statistical computing. 2015. R Foundation for Statistical Computing: Vienna, Austria.Google Scholar
50. Higashimoto, K, Jozaki, K, Kosho, T, et al. A novel de novo point mutation of the OCT-binding site in the IGF2/H19-imprinting control region in a Beckwith-Wiedemann syndrome patient. Clin Genet. 2014; 86, 539–544.Google Scholar
51. Abi Habib, W, Azzi, S, Brioude, F, et al. Extensive investigation of the IGF2/H19 imprinting control region reveals novel OCT4/SOX2 binding site defects associated with specific methylation patterns in Beckwith-Wiedemann syndrome. Hum Mol Genet. 2014; 23, 5763–5773.Google Scholar
52. Loke, YJ, Galati, JC, Morley, R, et al. Association of maternal and nutrient supply line factors with DNA methylation at the imprinted IGF2/H19 locus in multiple tissues of newborn twins. Epigenetics. 2013; 8, 1069–1079.Google Scholar
53. He, J, Zhang, A, Fang, M, et al. Methylation levels at IGF2 and GNAS DMRs in infants born to preeclamptic pregnancies. BMC Genomics. 2013; 14, 472.Google Scholar
54. Hoyo, C, Fortner, K, Murtha, AP, et al. 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.Google Scholar
55. Murphy, SK, Adigun, A, Huang, Z, et al. Gender-specific methylation differences in relation to prenatal exposure to cigarette smoke. Gene. 2012; 494, 36–43.CrossRefGoogle ScholarPubMed
56. Nawathe, AR, Christian, M, Kim, SH, et al. Insulin-like growth factor axis in pregnancies affected by fetal growth disorders. Clin Epigenetics. 2016; 8, 11.Google Scholar
57. Johansson, A, Enroth, S, Gyllensten, U. Continuous aging of the human DNA methylome throughout the human lifespan. PLoS One. 2013; 8, e67378.Google Scholar
58. Reynolds, LM, Taylor, JR, Ding, J, et al. Age-related variations in the methylome associated with gene expression in human monocytes and T cells. Nat Commun. 2014; 5, 5366.Google Scholar
59. Chriett, S, Le Huërou-Luron, I, Vidal, H, Pirola, L. Dysregulation of sirtuins and key metabolic genes in skeletal muscle of pigs with spontaneous intrauterine growth restriction is associated with alterations of circulating IGF-1. Gen Comp Endocrinol. 2016; 232, 76–85.Google Scholar
60. Bogic, M, Njoku, A, Priebe, S. Long-term mental health of war-refugees: a systematic literature review. BMC Int Health Hum Rights. 2015; 15, 29.Google Scholar
61. Organization WH. WHO Multi-Country Study on Women’s Health and Domestic Violence against Women. 2005.Google Scholar
62. Moore, KA, Simpson, JA, Thomas, KH, et al. Estimating gestational age in late presenters to antenatal care in a resource-limited setting on the Thai-Myanmar border. PLoS One. 2015; 10, e0131025.Google Scholar
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