Article

Birthweight is associated with DNA promoter methylation of the glucocorticoid receptor in human placenta

Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA.
Epigenetics: official journal of the DNA Methylation Society (Impact Factor: 5.11). 05/2011; 6(5):566-72. DOI: 10.4161/epi.6.5.15236
Source: PubMed

ABSTRACT Birthweight has been associated with a number of health outcomes throughout life. Crucial to proper infant growth and development is the placenta, and alterations to placental gene function may reflect differences in the intrauterine environment which functionally contribute to infant growth and may ultimately affect the child's health. To examine if epigenetic alteration to the glucocorticoid receptor (GR) gene was linked to infant growth, we analyzed 480 human placentas for differential methylation of the GR gene exon 1F and examined how this variation in methylation extent was associated with fetal growth. Multivariable linear regression revealed a significant association (p < 0.0001) between differential methylation of the GR gene and large for gestational age (LGA) status. Our work is one of the first to link infant growth as a measure of the intrauterine environment and epigenetic alterations to the GR and suggests that DNA methylation may be a critical determinant of placental function.

Download full-text

Full-text

Available from: Carolyn E Banister, Jul 03, 2015
0 Followers
 · 
134 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Early life environments interact with genotype to determine stable phenotypic outcomes. Here we examined the influence of a variant in the brain-derived neurotropic factor (BDNF) gene (Val66Met), which underlies synaptic plasticity throughout the central nervous system, on the degree to which antenatal maternal anxiety associated with neonatal DNA methylation. We also examined the association between neonatal DNA methylation and brain substructure volume, as a function of BDNF genotype. Infant, but not maternal, BDNF genotype dramatically influences the association of antenatal anxiety on the epigenome at birth as well as that between the epigenome and neonatal brain structure. There was a greater impact of antenatal maternal anxiety on the DNA methylation of infants with the methionine (Met)/Met compared to both Met/valine (Val) and Val/Val genotypes. There were significantly more cytosine-phosphate-guanine sites where methylation levels covaried with right amygdala volume among Met/Met compared with both Met/Val and Val/Val carriers. In contrast, more cytosine-phosphate-guanine sites covaried with left hippocampus volume in Val/Val infants compared with infants of the Met/Val or Met/Met genotype. Thus, antenatal Maternal Anxiety × BDNF Val66Met Polymorphism interactions at the level of the epigenome are reflected differently in the structure of the amygdala and the hippocampus. These findings suggest that BDNF genotype regulates the sensitivity of the methylome to early environment and that differential susceptibility to specific environmental conditions may be both tissue and function specific.
    Development and Psychopathology 02/2015; 27(1):137-50. DOI:10.1017/S0954579414001357 · 4.89 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objectives. Transmission of parental post-traumatic stress disorder (PTSD) to offspring might be explained by transmission of epigenetic processes such as methylation status of the glucocorticoid receptor (GR) gene (NR3C1). Methods. We investigated PTSD and depression severity, plasma cortisol, GR and mineralocorticoid receptor (MR) levels, and methylation status of NR3C1 and NR3C2 promoter regions in 25 women exposed to the Tutsi genocide during pregnancy and their children, and 25 women from the same ethnicity, pregnant during the same period but not exposed to the genocide, and their children. Results. Transmission of PTSD to the offspring was associated with transmission of biological alterations of the HPA axis. Mothers exposed to the genocide as well as their children had lower cortisol and GR levels and higher MR levels than non-exposed mothers and their children. Moreover, exposed mothers and their children had higher methylation of the NR3C1 exon 1F than non-exposed groups. Finally, exposed mothers showed higher methylation of CpGs located within the NR3C2 coding sequence than non-exposed mothers. Conclusions. PTSD was associated with NR3C1 epigenetic modifications that were similarly found in the mothers and their offspring, modifications that may underlie the possible transmission of biological alterations of the HPA axis.
    The World Journal of Biological Psychiatry 04/2014; 15(4). DOI:10.3109/15622975.2013.866693 · 4.23 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Although the association between maternal smoking and low birthweight infants has been well established, the mechanisms behind reduced fetal growth are still being elucidated. While many infants are exposed to tobacco smoke in utero, not all are born growth restricted or small for gestational age (SGA). Many hypotheses have emerged to explain the differential response to in utero maternal tobacco smoke exposure (MTSE). Studies have shown that both maternal and fetal genotypes may contribute to the discrepant outcomes. However, the contribution of epigenetic changes cannot be ignored. In this review we address two important questions regarding the effect of MTSE on the fetal epigenome. First, does exposure to maternal tobacco smoke in utero alter the fetal epigenome? Second, could these alterations be associated with the reduced fetal growth observed with MTSE?
    Molecular Human Reproduction 11/2012; DOI:10.1093/molehr/gas050 · 3.48 Impact Factor