Choice of surrogate tissue influences neonatal EWAS findings

Background

Epigenomes are tissue specific and thus the choice of surrogate tissue can play a critical role in interpreting neonatal epigenome-wide association studies (EWAS) and in their extrapolation to target tissue. To develop a better understanding of the link between tissue specificity and neonatal EWAS, and the contributions of genotype and prenatal factors, we compared genome-wide DNA methylation of cord tissue and cord blood, two of the most accessible surrogate tissues at birth.

Methods

In 295 neonates, DNA methylation was profiled using Infinium HumanMethylation450 beadchip arrays. Sites of inter-individual variability in DNA methylation were mapped and compared across the two surrogate tissues at birth, i.e., cord tissue and cord blood. To ascertain the similarity to target tissues, DNA methylation profiles of surrogate tissues were compared to 25 primary tissues/cell types mapped under the Epigenome Roadmap project. Tissue-specific influences of genotype on the variable CpGs were also analyzed. Finally, to interrogate the impact of the in utero environment, EWAS on 45 prenatal factors were performed and compared across the surrogate tissues.

Results

Neonatal EWAS results were tissue specific. In comparison to cord blood, cord tissue showed higher inter-individual variability in the epigenome, with a lower proportion of CpGs influenced by genotype. Both neonatal tissues were good surrogates for target tissues of mesodermal origin. They also showed distinct phenotypic associations, with effect sizes of the overlapping CpGs being in the same order of magnitude.

Conclusions

The inter-relationship between genetics, prenatal factors and epigenetics is tissue specific, and requires careful consideration in designing and interpreting future neonatal EWAS.

Trial registration

This birth cohort is a prospective observational study, designed to study the developmental origins of health and disease, and was retrospectively registered on 1 July 2010 under the identifier NCT01174875.

     

速度向量成像技术对正常胎儿心肌运动的评价及其意义

目的探讨速度向量成像技术(VVI)在评价胎儿室壁心肌功能中的作用及其影响因素。方法通过Syngo US Workplace VVI工作站处理标准胎儿四腔心动态图(147例),分别获得左、右心室四腔心观心内膜VVI图,以及左、右心室纵向6个节段的速度、应变、应变率的测值并进行分析。结果 (1)左、右心室的速度分布由基底段向心尖逐渐减小(P0.05),其6个节段和整体的应变、应变率的差异无统计学意义(P0.05)。(2)左、右心室的速度和孕周呈正相关(左心室r=0.662,P0.05;右心室r=0.732,P0.05),整体应变、应变率和孕周无显著相关性(P0.05)。(3)左、右心室整体应变率和胎心率呈正相关(左心室r=0.454,P0.05;右心室r=0.465,P0.05),其应变和速度均和胎心率无显著相关性(P0.05)。结论 VVI技术可应用于胎儿整体和局部心肌运动和功能的分析评估。     

口服大剂量米非司酮对子宫内膜癌细胞凋亡和端粒酶活性的影响

目的：研究口服大剂量米非司酮对子宫内膜癌细胞凋亡和端粒酶活性的影响，并探讨其作用机制。方法：12例未治疗的子宫内膜癌患者口服大剂量米非司酮（100mg/d,共5天）。第六天手术，用免疫组织化学法（LSAB法）检测用药前后内膜癌组织Fas、FasL表达的变化。用半定量端粒重复序列扩增法（semiquantitative telomere repeat amplification protocol,TRAP)测定用药前后内膜癌组织端粒酶活性的改变。结果：口服大剂量米非司酮后子宫内膜Fas表达明显升高（P＜0.01),FasL表达及端粒酶活性无明显改变（P＞0.05)。结论：口服大剂量米非司酮可促进子宫内膜癌细胞凋亡，但对端粒酶活性无明显影响。