Prenatal Maternal Stress Predicts Methylation of Genes Regulating the Hypothalamic-Pituitary-Adrenocortical System in Mothers and Newborns in the Democratic Republic of Congo.
Prenatal Maternal Stress Predicts Methylation of Genes Regulating the Hypothalamic-Pituitary-Adrenocortical System in Mothers and Newborns in the Democratic Republic of Congo.
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DOI：
10.1111/cdev.12487
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发表时间：
2016-01
影响因子：
4.6
通讯作者：
Mulligan CJ
中科院分区：
文献类型：
--
作者：
Kertes DA;Kamin HS;Hughes DA;Rodney NC;Bhatt S;Mulligan CJ
生命早期暴露于压力会永久影响下丘脑-垂体-肾上腺皮质 (HPA) 轴和大脑的活动。产前，糖皮质激素通过胎盘传递给胎儿，对产后大脑发育、出生体重和 HPA 轴功能产生影响。对于产前应激影响产后功能的生物学机制知之甚少。本研究通过研究慢性应激和创伤性战争相关应激对调节新生儿脐带血、胎盘和母血中 HPA 轴的四个关键基因（CRH、CRHBP、NR3C1 和 FKBP5）表观遗传变化的影响来解决这一差距。参与者是刚果民主共和国东部冲突地区的 24 名母亲和新生儿。在分娩时收集出生体重数据，并进行产妇访谈，以评估文化相关的慢性和战争相关压力源。慢性应激和战争创伤对 HPA 轴基因甲基化具有广泛影响，在所有测试的靶基因的转录因子结合位点均观察到显着影响。甲基化的一些变化是慢性压力或战争压力所特有的，而另一些变化则在两种压力源类型中都观察到。此外，压力暴露对母体和胎儿组织的影响不同，支持压力影响根据生命阶段而变化的理论模型。几个 NR3C1 和 CRH CpG 位点的甲基化（全部位于转录因子结合位点）与出生体重相关。这些发现表明，产前压力暴露通过 HPA 轴基因的表观遗传变化影响发育。
Exposure to stress early in life permanently shapes activity of the hypothalamic-pituitary-adrenocortical (HPA) axis and the brain. Prenatally, glucocorticoids pass through the placenta to the fetus with postnatal impacts on brain development, birth weight, and HPA axis functioning. Little is known about the biological mechanisms by which prenatal stress affects postnatal functioning. This study addresses this gap by examining the effect of chronic stress and traumatic war-related stress on epigenetic changes in four key genes regulating the HPA axis in neonatal cord blood, placenta, and maternal blood: CRH, CRHBP, NR3C1, and FKBP5. Participants were 24 mother-newborn dyads in the conflict-ridden region of the eastern Democratic Republic of Congo. Birth weight data were collected at delivery and maternal interviews were conducted to assess culturally relevant chronic and war-related stressors. Chronic stress and war trauma had widespread effects on HPA axis gene methylation, with significant effects observed at transcription factor binding sites in all target genes tested. Some changes in methylation were unique to chronic or war stress, whereas others were observed across both stressor types. Moreover, stress exposures impacted maternal and fetal tissues differently, supporting theoretical models that stress impacts vary according to life phase. Methylation in several NR3C1 and CRH CpG sites, all located at transcription factor binding sites, was associated with birth weight. These findings suggest that prenatal stress exposure impacts development via epigenetic changes in HPA axis genes.