Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC.
Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC.
Ann Glob Health. 2016 Jan-Feb;82(1):189-96. doi: 10.1016/j.aogh.2016.01.015.
Prenatal exposure to inorganic arsenic (iAs) is associated with dysregulated fetal gene and protein expression. Potential biological mechanisms that underlie these changes include, but are not limited to, changes to the epigenome.
The aim of the present study was to identify whether the expression of key genes, proteins, or both and their associated biological pathways are perturbed by compiling datasets from studies on prenatal arsenic exposure.
We compiled datasets from 12 studies that analyzed the relationship between prenatal iAs exposure and changes to the fetal epigenome (5-methyl cytosine), transcriptome (mRNA expression), and/or proteome (protein expression).
Across the 12 studies, a set of 845 unique genes was identified and found to enrich for their role in biological pathways, including the peroxisome proliferator-activated receptor, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, and the glucocorticoid receptor. Tumor necrosis factor was identified as a putative cellular regulator underlying most (n = 277) of the identified iAs-associated gene or protein expression changes.
The identification of the common set of genes across numerous human cohorts suggests a conserved biological response to prenatal arsenic exposure. The genes/proteins and their associated pathways may be useful in future mechanistic investigations of iAs associated diseases.
产前无机砷（iAs）暴露与胎儿基因和蛋白质表达失调有关。潜在的生物学机制包括但不限于表观基因组的改变。
本研究旨在通过整合产前砷暴露研究的数据集，确定关键基因、蛋白质或两者的表达及其相关生物学途径是否受到干扰。
我们整合了 12 项研究的数据集，这些研究分析了产前 iAs 暴露与胎儿表观基因组（5-甲基胞嘧啶）、转录组（mRNA 表达）和/或蛋白质组（蛋白质表达）变化之间的关系。
在这 12 项研究中，确定了一组 845 个独特的基因，并发现它们在生物学途径中富集，包括过氧化物酶体增殖物激活受体、κB 轻链增强子核因子抑制剂和糖皮质激素受体。肿瘤坏死因子被确定为大多数（n=277）鉴定的 iAs 相关基因或蛋白质表达变化的潜在细胞调节剂。
在许多人类队列中鉴定出的共同基因集表明，对产前砷暴露存在保守的生物学反应。这些基因/蛋白质及其相关途径可能有助于未来对 iAs 相关疾病的机制研究。
