Sanne D. van Otterdijk , Alexandra M. Binder , Karin B. Michels
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引用次数: 0
摘要
导言:新生儿的炎症反应可能部分是在发育过程中由胎盘表观基因组形成的,但这方面的证据还很少。我们研究了胎盘 DNA 甲基化与脐带血中促炎蛋白之间的关联:本研究共纳入了哈佛表观遗传出生队列中的 249 对母子。使用Illumina人类甲基化450珠芯片阵列评估胎盘DNA的全基因组甲基化,并通过热测序进行验证。评估的脐带血炎症标记物包括白细胞介素-6、白细胞介素-8和肿瘤坏死因子α、细胞间粘附分子1、血清淀粉样蛋白A和C反应蛋白:结果:我们发现HIVEP3基因岸区的三个位点的胎盘DNA甲基化差异与脐带血中的TNFα蛋白水平有关。TNFα水平与分娩方式、胎龄和胎次有关。位于BCL11B基因开放海区的另外三个位点与脐带血中的SAA蛋白水平有关。SAA水平与出生体重、胎龄和婴儿性别有关:我们的研究结果表明,HIVEP3 和 BCL11B 胎盘 DNA 甲基化在新生儿急性免疫反应中的潜在作用。这些免疫标记物与母婴的一些特征相关。
Placental methylation and pro-inflammatory protein levels in cord blood
Introduction
The neonates’ inflammatory response may in part be shaped during development by the placental epigenome, but evidence is scarce. We investigated the association between placental DNA methylation and pro-inflammatory proteins in cord blood.
Methods
A total of 249 mother-child dyads from the Harvard Epigenetic Birth Cohort were included in this study. Genome-wide methylation in placental DNA was assessed using the Illumina Human Methylation 450 Bead Chip array and verified by pyrosequencing. Cord blood inflammation markers assessed were interleukin-6, interleukin-8 and tumor necrosis factor α, intercellular adhesion molecule 1, serum amyloid A, and C-reactive protein.
Results
We identified differential placental DNA methylation of three loci in the HIVEP3 gene shore region that were associated with TNFα protein levels in cord blood. TNFα levels were associated with mode of delivery, gestational age and birth order. Three other loci located in the open sea region of the BCL11B gene were associated with SAA protein levels in cord blood. SAA levels were associated with birthweight, gestational age, and infant sex.
Conclusions
Our results suggest a potential role for HIVEP3 and BCL11B placental DNA methylation in the acute immune response of the neonate. These immune markers were correlated with several mother and child characteristics.
期刊介绍:
Placenta publishes high-quality original articles and invited topical reviews on all aspects of human and animal placentation, and the interactions between the mother, the placenta and fetal development. Topics covered include evolution, development, genetics and epigenetics, stem cells, metabolism, transport, immunology, pathology, pharmacology, cell and molecular biology, and developmental programming. The Editors welcome studies on implantation and the endometrium, comparative placentation, the uterine and umbilical circulations, the relationship between fetal and placental development, clinical aspects of altered placental development or function, the placental membranes, the influence of paternal factors on placental development or function, and the assessment of biomarkers of placental disorders.