Chen Jia, Li Qian, Rialdi Alexender, Mystal Elana, Ly Jenny, Finik Jackie, Davey Taira, Lambertini Luca, Nomura Yoko
Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
J Depress Anxiety. 2014;3(2). doi: 10.4172/2167-1044.1000152. Epub 2014 Feb 25.
Maternal stress during pregnancy is one of the major adverse environmental factors in utero that is capable of influencing health outcomes of the offspring throughout life. Both genetic and epigenetic processes are susceptible to environmental insults in utero and are potential biomarkers of the experienced environment including maternal stress.
We profiled expression level of six genes in hypothalamic pituitary adrenal (HPA) axis functioning (HSD11B2, SLC6A4, NR3C1, NR3C2, CRHR1 and CRHR2), two imprinted genes (IGF2 and H19) and one neurodevelopmental gene (EGR1), from 49 pairs of placenta and umbilical cord blood (UCB) samples from a birth cohort. We also assessed global methylation levels by LUminometric Methylation Assay (LUMA) and methylation at the imprinting control region (ICR) of IGF2/H19.
Little correlations between paired placenta and UCB were observed except H19 expression (r = 0.31, P = 0.04) and IGF2/H19 ICR methylation (r = 0.43, P = 0.01); gene expression levels were significantly higher (P < 0.001) in placenta than UCB except CRHR1 and CRHR2, which were unexpressed in placenta. Maternal stress correlated higher levels of HPA genes and lower levels of EGR1 and LUMA, but only in placenta. Positive association between maternal stress and IGF2/H19 ICR methylation was present in both placenta and UCB.
Our findings support the notion that adverse in utero environment, as measured by antenatal maternal stress, depression and anxiety, can be observed in the epi/genome of the relevant tissues, i.e. placenta and UCBs, leading to development of molecular markers for assessing in utero adversities.
孕期母亲压力是子宫内主要的不良环境因素之一，能够影响子代一生的健康结局。遗传和表观遗传过程均易受子宫内环境损伤影响，并且是包括母亲压力在内的所经历环境的潜在生物标志物。
我们分析了来自一个出生队列的49对胎盘和脐带血（UCB）样本中，下丘脑-垂体-肾上腺（HPA）轴功能相关的6个基因（HSD11B2、SLC6A4、NR3C1、NR3C2、CRHR1和CRHR2）、2个印记基因（IGF2和H19）以及1个神经发育基因（EGR1）的表达水平。我们还通过荧光定量甲基化分析（LUMA）评估了整体甲基化水平以及IGF2/H19印记控制区（ICR）的甲基化情况。
除了H19表达（r = 0.31，P = 0.04）和IGF2/H19 ICR甲基化（r = 0.43，P = 0.01）外，胎盘和脐带血之间几乎没有相关性；除CRHR1和CRHR2在胎盘中未表达外，基因表达水平在胎盘中显著高于脐带血（P < 0.001）。母亲压力与较高水平的HPA基因以及较低水平的EGR1和LUMA相关，但仅在胎盘中如此。母亲压力与IGF2/H19 ICR甲基化在胎盘和脐带血中均呈正相关。
我们的研究结果支持以下观点，即通过产前母亲压力、抑郁和焦虑所衡量的子宫内不良环境，可以在相关组织即胎盘和脐带血的表观/基因组中观察到，从而导致用于评估子宫内不良情况的分子标志物的出现。
