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. 2011 Jul 19;1(7):e21.
doi: 10.1038/tp.2011.21.

Transgenerational Impact of Intimate Partner Violence on Methylation in the Promoter of the Glucocorticoid Receptor

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Free PMC article

Transgenerational Impact of Intimate Partner Violence on Methylation in the Promoter of the Glucocorticoid Receptor

K M Radtke et al. Transl Psychiatry. .
Free PMC article

Abstract

Prenatal exposure to maternal stress can have lifelong implications for psychological function, such as behavioral problems and even the development of mental illness. Previous research suggests that this is due to transgenerational epigenetic programming of genes operating in the hypothalamic-pituitary-adrenal axis, such as the glucocorticoid receptor (GR). However, it is not known whether intrauterine exposure to maternal stress affects the epigenetic state of these genes beyond infancy. Here, we analyze the methylation status of the GR gene in mothers and their children, at 10-19 years after birth. We combine these data with a retrospective evaluation of maternal exposure to intimate partner violence (IPV). Methylation of the mother's GR gene was not affected by IPV. For the first time, we show that methylation status of the GR gene of adolescent children is influenced by their mother's experience of IPV during pregnancy. As these sustained epigenetic modifications are established in utero, we consider this to be a plausible mechanism by which prenatal stress may program adult psychosocial function.

Figures

Figure 1
Figure 1
Degree of methylation per individual and CpG site. Each line represents the analyzed fraction of the glucocorticoid receptor gene of a woman (Mu) and her child (Ki). The rows correspond to individual CpG sites. The degree of methylation for each individual CpG site, that is, the number of clones containing methylation in the particular site divided by the total number of sequenced clones, is colour-coded. In the case of one child we could not obtain a blood sample as indicated by ‘no data'. (i) Putative NGFI-A-binding site; (ii) Known NGFI-A-binding site.
Figure 2
Figure 2
Gestational effects of IPV on methylation of the GR promoter in the children. Mean±s.e.m. of percentage of methylated clones for the children of women exposed to IPV. IPV only associates with increased methylation, if maternal exposure occurred during pregnancy. The percentage of methylated clones was calculated as the number of clones containing at least one methylated CpG site divided by the total number of clones. *P<0.05; IPV, intimate partner violence.

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