Transgenerational impact of intimate partner violence on methylation in the promoter of the glucocorticoid receptor

TLDR

Prenatal maternal stress can cause lifelong psychological problems, possibly via transgenerational epigenetic programming of HPA‑axis genes such as the glucocorticoid receptor, yet it is unclear whether such epigenetic changes persist beyond infancy. The study aimed to examine whether maternal intimate partner violence during pregnancy alters methylation of the glucocorticoid receptor gene in mothers and their adolescent offspring. Researchers measured GR promoter methylation in mothers and their children aged 10–19 and linked these data to a retrospective assessment of maternal IPV exposure. Maternal IPV did not change mothers’ GR methylation, but it was associated with increased methylation of the GR gene in adolescent children, suggesting prenatal stress establishes lasting epigenetic modifications that may program adult psychosocial function.

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.