The roles of DNA methylation of NR3C1 and 11β-HSD2 and exposure to maternal mood disorder in utero on newborn neurobehavior
The roles of DNA methylation of NR3C1 and 11β-HSD2 and exposure to maternal mood disorder in utero on newborn neurobehavior
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DOI：
10.4161/epi.26634
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发表时间：
2013-12-01
期刊：
影响因子：
3.7
通讯作者：
Marsit, Carmen J.
中科院分区：
文献类型：
--
作者：
Conradt, Elisabeth;Lester, Barry M.;Marsit, Carmen J.
在子宫内暴露于母亲的情绪障碍可能会通过糖皮质激素受体（NR3C1）和11-羟基类固醇脱氢酶2型（11-HSD-2）的DNA甲基化来编程婴儿的神经行为，这两个胎盘基因与下丘脑-垂体-肾上腺皮质（HPA）轴的扰动有关。我们测试了产前暴露于母亲抑郁或焦虑、NR3C1和11-HSD-2外显子1F甲基化和新生儿神经行为之间的关系。在控制相关协变量的情况下，母亲在怀孕期间报告抑郁、胎盘NR3C1 CpG2甲基化程度较高的婴儿，其自我调节能力较差、张力低下和嗜睡程度高于母亲未报告抑郁的婴儿。另一方面，母亲在怀孕期间报告焦虑的婴儿与母亲在怀孕期间没有报告焦虑的婴儿相比，胎盘11-HSD-2 CpG4甲基化程度更高。我们的研究结果支持胎儿编程假说，并表明胎儿对宫内环境的调节，在这种情况下，可能以母体皮质醇暴露增加为特征的环境，可能导致不良的神经发育结果。
Exposure to maternal mood disorder in utero may program infant neurobehavior via DNA methylation of the glucocorticoid receptor (NR3C1) and 11-hydroxysteroid dehydrogenase type 2 (11-HSD-2), two placental genes that have been implicated in perturbations of the hypothalamic pituitary adrenocortical (HPA) axis. We tested the relations among prenatal exposure to maternal depression or anxiety, methylation of exon 1F of NR3C1 and 11-HSD-2, and newborn neurobehavior. Controlling for relevant covariates, infants whose mothers reported depression during pregnancy and showed greater methylation of placental NR3C1 CpG2 had poorer self-regulation, more hypotonia, and more lethargy than infants whose mothers did not report depression. On the other hand, infants whose mothers reported anxiety during pregnancy and showed greater methylation of placental 11-HSD-2 CpG4 were more hypotonic compared with infants of mothers who did not report anxiety during pregnancy. Our results support the fetal programming hypothesis and suggest that fetal adjustments to cues from the intrauterine environment, in this case an environment that could be characterized by increased exposure to maternal cortisol, may lead to poor neurodevelopmental outcomes.