Clinical Psychology and Neuropsychology, Department of Psychology, University of Konstanz, Konstanz, Germany.
Evolutionary Biology and Zoology, Department of Biology, University of Konstanz, Konstanz, Germany.
Transl Psychiatry. 2017 Aug 15;7(8):e1202. doi: 10.1038/tp.2017.153.
Stress during pregnancy may impact subsequent generations, which is demonstrated by an increased susceptibility to childhood and adulthood health problems in the children and grandchildren. Although the importance of the prenatal environment is well reported with regards to future physical and emotional outcomes, little is known about the molecular mechanisms that mediate the long-term consequences of early stress across generations. Recent studies have identified DNA methylation as a possible mediator of the impact of prenatal stress in the offspring. Whether psychosocial stress during pregnancy also affects DNA methylation of the grandchildren is still not known. In the present study we examined the multigenerational hypothesis, that is, grandmaternal exposure to psychosocial stress during pregnancy affecting DNA methylation of the grandchildren. We determined the genome-wide DNA methylation profile in 121 children (65 females and 56 males) and tested for associations with exposure to grandmaternal interpersonal violence during pregnancy. We observed methylation variations of five CpG sites significantly (FDR<0.05) associated with the grandmother's report of exposure to violence while pregnant with the mothers of the children. The results revealed differential methylation of genes previously shown to be involved in circulatory system processes (FDR<0.05). This study provides support for DNA methylation as a biological mechanism involved in the transmission of stress across generations and motivates further investigations to examine prenatal-dependent DNA methylation as a potential biomarker for health problems.
孕期压力可能会影响后代，这表现在孩子和孙辈更容易出现儿童期和成年期健康问题。尽管产前环境对未来的身体和情绪结果的重要性已有充分报道，但对于早期压力在代际间产生长期影响的分子机制知之甚少。最近的研究已经确定 DNA 甲基化为产前压力对后代影响的可能介导者。孕期的心理社会压力是否也会影响孙辈的 DNA 甲基化尚不清楚。在本研究中，我们检验了多代假设，即祖母在孕期受到心理社会压力的影响会影响孙辈的 DNA 甲基化。我们确定了 121 名儿童（65 名女性和 56 名男性）的全基因组 DNA 甲基化图谱，并测试了与祖母在孕期遭受人际暴力的暴露情况之间的关联。我们观察到与儿童母亲的祖母在孕期遭受暴力的报告相关的五个 CpG 位点的甲基化变化具有显著意义（FDR<0.05）。结果显示，先前显示与循环系统过程相关的基因的甲基化存在差异（FDR<0.05）。本研究为 DNA 甲基化为跨代传递压力的生物学机制提供了支持，并促使进一步研究将产前依赖的 DNA 甲基化作为健康问题的潜在生物标志物进行检验。
