Adverse Maternal Metabolic Intrauterine Environment and Placental Epigenetics: Implications for Fetal Metabolic Programming
Purpose of Review
Herein, we summarize existent epidemiological studies relating adverse maternal metabolic environments of maternal obesity and gestational diabetes and placental DNA methylation.
Multiple studies have evaluated associations between intrauterine exposure to gestational diabetes and/or maternal glucose levels and DNA methylation at candidate metabolic genes as well as in epigenome-wide studies. Some of the genomic regions more consistently associated include lipid-related genes (LPL and PPARGC1A), the major histocompatibility complex (MHC), and imprinted genes. Studies solely focused on maternal obesity influences on the placental epigenome are scarce.
Understanding the placental mechanisms involved in fetal metabolic programming could lead to discovery of placental biomarkers at birth that predict later-life metabolic risk. Moving forward is important to standardize methods utilized in epigenetics research; consistent methodology can help interpret disparate findings. Larger studies with longitudinal follow-up are needed to address future challenges in fetal programming research.
KeywordsEpigenetics Placenta Maternal obesity Gestational diabetes Metabolic programming
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflicts of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the author.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 1.Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet (London, England). 2014;384(9945):766–81.CrossRefGoogle Scholar
- 3.• Poston L, Caleyachetty R, Cnattingius S, Corvalan C, Uauy R, Herring S, et al. Preconceptional and maternal obesity: epidemiology and health consequences. Lancet Diabetes Endocrinol. 2016;4(12):1025–36 Recent summary of the margnigtude of the maternal obesity problem and its possible consequences.CrossRefGoogle Scholar
- 14.Poston L, Harthoorn LF, Van Der Beek EM. Obesity in pregnancy: implications for the mother and lifelong health of the child. A consensus statement. Pediatric Res. 2011;69(2):175–180.Google Scholar
- 19.Ravelli AC, van der Meulen JH, Michels RP, Osmond C, Barker DJ, Hales CN, et al. Glucose tolerance in adults after prenatal exposure to famine. Lancet (London, England). 1998;351(9097):173–7.Google Scholar
- 20.Ravelli AC, van der Meulen JH, Osmond C, Barker DJ, Bleker OP. Obesity at the age of 50 y in men and women exposed to famine prenatally. Am J Clin Nutr. 1999;70(5):811–816.Google Scholar
- 37.Lesseur C, Armstrong DA, Paquette AG, Li Z, Padbury JF, Marsit CJ. Maternal obesity and gestational diabetes are associated with placental leptin DNA methylation. Am J Obstet Gynecol. 2014;211(6):654.e1–9.Google Scholar
- 38.Bouchard L, Hivert MF, Guay SP, St-Pierre J, Perron P, Brisson D. Placental adiponectin gene DNA methylation levels are associated with mothers’ blood glucose concentration. Diabetes. 2012;61(5):1272–1280.Google Scholar
- 41.• Gagne-Ouellet V, Houde AA, Guay SP, Perron P, Gaudet D, Guerin R, et al. Placental lipoprotein lipase DNA methylation alterations are associated with gestational diabetes and body composition at 5 years of age. Epigenetics. 2017;12(8):616–25 Firt study that relate placental epigenetic marks to 5-year olf weight outomes. Google Scholar
- 42.Xie X, Gao H, Zeng W, Chen S, Feng L, Deng D, et al. Placental DNA methylation of peroxisome-proliferator-activated receptor-gamma co-activator-1alpha promoter is associated with maternal gestational glucose level. Clin Sci (London, England: 1979). 2015;129(4):385–94.Google Scholar
- 46.Jolly MC, Sebire NJ, Harris JP, Regan L, Robinson S. Risk factors for macrosomia and its clinical consequences: a study of 350,311 pregnancies. Eur J Obstet Gynecol Reprod Biol. 2003;111(1):9–14.Google Scholar
- 48.Lavery JA, Friedman AM, Keyes KM, Wright JD, Ananth CV. Gestational diabetes in the United States: temporal changes in prevalence rates between 1979 and 2010. BJOG: an international journal of obstetrics and gynecology. 2017;124(5):804–813.Google Scholar
- 49.Weaver IC, Cervoni N, Champagne FA, D’Alessio AC, Sharma S, Seckl JR, et al. Epigenetic programming by maternal behavior. Nat Neurosc. 2004;7(8):847–854.Google Scholar
- 55.Nomura Y, Lambertini L, Rialdi A, Lee M, Mystal EY, Grabie M, et al. Global methylation in the placenta and umbilical cord blood from pregnancies with maternal gestational diabetes, preeclampsia, and obesity. Reprod Sci (Thousand Oaks, Calif). 2014;21(1):131–7.Google Scholar
- 60.Cardenas A, Gagne-Ouellet V, Allard C, Brisson D, Perron P, Bouchard L, et al. Placenta DNA Methylation Adaptation to Maternal Glycemic Response in Pregnancy. Diabetes. 2018.Google Scholar
- 66.Dendrou CA, Petersen J, Rossjohn J, Fugger L. HLA variation and disease. Nat Rev Immunol. 2018.Google Scholar
- 67.•• Felix JF, Joubert BR, Baccarelli AA, Sharp GC, Almqvist C, Annesi-Maesano I, et al. Cohort Profile: Pregnancy And Childhood Epigenetics (PACE) Consortium. Int J Epidemiol. 2018;47(1):22–3u Recent outline of current epigenetics research on children’s health including best practices for epigenome-wide studies. Google Scholar
- 68.• Breton CV, Marsit CJ, Faustman E, Nadeau K, Goodrich JM, Dolinoy DC, et al. Small-Magnitude Effect Sizes in Epigenetic End Points are Important in Children’s Environmental Health Studies: The Children’s Environmental Health and Disease Prevention Research Center’s Epigenetics Working Group. Environ Health Perspect. 2017;125(4):511–26 Largest GDM-related EWAS to date using placental tissue. Google Scholar