Synthetic glucocorticoids (sGC) are administered to women at risk of preterm delivery, approximately 10% of all pregnancies. In animal models, offspring exposed to elevated glucocorticoids, either by administration of sGC or endogenous glucocorticoids as a result of maternal stress, show increased risk of developing behavioral, endocrine, and metabolic dysregulation. DNA methylation may play a critical role in long-lasting programming of gene regulation underlying these phenotypes. However, peripheral tissues such as blood are often the only accessible source of DNA for epigenetic analyses in humans. Here, we examined the hypothesis that prenatal sGC administration alters DNA methylation signatures in guinea pig offspring hippocampus and whole blood. We compared these signatures across the two tissue types to assess epigenetic biomarkers of common molecular pathways affected by sGC exposure. Guinea pigs were treated with sGC or saline in late gestation. Genome-wide modifications of DNA methylation were analyzed at single nucleotide resolution using reduced representation bisulfite sequencing in juvenile female offspring. Results indicate that there are tissue-specific as well as common methylation signatures of prenatal sGC exposure. Over 90% of the common methylation signatures associated with sGC exposure showed the same directionality of change in methylation. Among differentially methylated genes, 134 were modified in both hippocampus and blood, of which 61 showed methylation changes at identical CpG sites. Gene pathway analyses indicated that prenatal sGC exposure alters the methylation status of gene clusters involved in brain development. These data indicate concordance across tissues of epigenetic programming in response to alterations in glucocorticoid signaling.

合成糖皮质激素（sGC）用于有早产风险的妇女，约占所有怀孕妇女的10％。在动物模型中，由于母体压力而通过施用sGC或内源性糖皮质激素而暴露于糖皮质激素升高的后代，其发生行为，内分泌和代谢失调的风险增加。DNA甲基化可能在这些表型基础的基因调控的长期编程中发挥关键作用。然而，诸如血液的外围组织通常是人类表观遗传学分析中唯一可访问的DNA来源。在这里，我们检查了产前sGC施用改变豚鼠后代海马和全血中DNA甲基化标记的假说。我们比较了两种组织类型的这些特征，以评估受sGC暴露影响的常见分子途径的表观遗传标记。豚鼠在妊娠后期用sGC或生理盐水处理。使用减少的代表性亚硫酸氢盐测序，在未成年雌性后代中以单核苷酸分辨率分析了全基因组DNA甲基化修饰。结果表明，产前sGC暴露存在组织特异性以及常见的甲基化特征。超过90％的与sGC暴露相关的常见甲基化标记显示出相同的甲基化变化方向。在差异甲基化的基因中，海马和血液中有134个被修饰，其中61个在相同的CpG位点显示甲基化变化。基因途径分析表明，产前sGC暴露会改变参与大脑发育的基因簇的甲基化状态。这些数据表明响应糖皮质激素信号变化的表观遗传编程的组织之间的一致性。