Patterning in Placental 11-B Hydroxysteroid Dehydrogenase Methylation According to Prenatal Socioeconomic Adversity
Patterning in Placental 11-B Hydroxysteroid Dehydrogenase Methylation According to Prenatal Socioeconomic Adversity
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DOI：
10.1371/journal.pone.0074691
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发表时间：
2013-09-05
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：
Appleton, Allison A.;Armstrong, David A.;Marsit, Carmen J.
背景资料：产前社会经济逆境作为宫内暴露与一系列围产期结局相关，尽管解释机制尚不清楚。胎儿的发育可以通过胎盘功能的改变由宫内环境塑造。在胎盘中，HSD 11B 2基因编码11-β羟基类固醇脱氢酶，该酶负责母体皮质醇的失活，从而保护发育中的胎儿免受这种暴露。该基因受DNA甲基化调控，这种甲基化及其控制的表达已被证明易受来自母体环境的各种压力因素的影响。产前社会经济逆境和胎盘HSD 11B 2甲基化的关联尚未研究。根据疾病的发展起源框架，产前社会经济逆境可能会改变胎儿对出生后环境的反应，通过胎盘的功能表观遗传改变。因此，我们假设，产前社会经济逆境将与较少的HSD 11B 2 methylation.Methods和调查结果：我们研究了444名健康足月新生儿胎盘中的HSD 11B 2启动子区域的DNA甲基化和产前社会经济逆境的几个标志物之间的关联：母亲的教育，贫困，居住拥挤，烟草使用和累积风险。我们还研究了这种关联是否具有性别特异性。我们发现，母亲在怀孕期间经历了最大程度的社会经济逆境的婴儿胎盘HSD 11B 2甲基化程度最低，特别是男性。在调整混杂因素后，母亲受教育程度仍保持相关性（p
Background: Prenatal socioeconomic adversity as an intrauterine exposure is associated with a range of perinatal outcomes although the explanatory mechanisms are not well understood. The development of the fetus can be shaped by the intrauterine environment through alterations in the function of the placenta. In the placenta, the HSD11B2 gene encodes the 11-beta hydroxysteroid dehydrogenase enzyme, which is responsible for the inactivation of maternal cortisol thereby protecting the developing fetus from this exposure. This gene is regulated by DNA methylation, and this methylation and the expression it controls has been shown to be susceptible to a variety of stressors from the maternal environment. The association of prenatal socioeconomic adversity and placental HSD11B2 methylation has not been examined. Following a developmental origins of disease framework, prenatal socioeconomic adversity may alter fetal response to the postnatal environment through functional epigenetic alterations in the placenta. Therefore, we hypothesized that prenatal socioeconomic adversity would be associated with less HSD11B2 methylation.Methods and Findings: We examined the association between DNA methylation of the HSD11B2 promoter region in the placenta of 444 healthy term newborn infants and several markers of prenatal socioeconomic adversity: maternal education, poverty, dwelling crowding, tobacco use and cumulative risk. We also examined whether such associations were sex-specific. We found that infants whose mothers experienced the greatest levels of socioeconomic adversity during pregnancy had the lowest extent of placental HSD11B2 methylation, particularly for males. Associations were maintained for maternal education when adjusting for confounders (p