In utero bisphenol A concentration, metabolism, and global DNA methylation across matched placenta, kidney, and liver in the human fetus.
In utero bisphenol A concentration, metabolism, and global DNA methylation across matched placenta, kidney, and liver in the human fetus.
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DOI：
10.1016/j.chemosphere.2014.10.071
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发表时间：
2015-04
期刊：
影响因子：
8.8
通讯作者：
Dolinoy DC
中科院分区：
文献类型：
--
作者：
Nahar MS;Liao C;Kannan K;Harris C;Dolinoy DC
虽然尿液一直是人体生物监测的一个容易获得和可行的基质，但内部组织和器官的分析测量可以提供更准确的暴露评估，以了解疾病病因。这对于内分泌活性化合物双酚A（BPA）尤其重要，目前缺乏对人类发育敏感时期内剂量的研究。在此，BPA浓度，BPA特异性代谢酶基因表达，和全球DNA甲基化的特征，在三个匹配的组织，从选择性终止妊娠的第二个三个月的人类胎儿：胎盘，肝脏和肾脏（N=12各; N=36总）。与肝脏（游离：0.54-50.5 ng/g）相比，匹配胎盘（<0.05-25.4 ng/g）和肾脏（0.08-11.1 ng/g）样本中的BPA浓度较低。GUSB、UGT 2B 15、STS和SULT 1A 1的BPA特异性代谢基因表达在每种组织类型中不同;然而，结合和解结合表达模式在胎儿中相似。平均LINE 1和CCGG整体甲基化在胎盘中为58.3%和59.2%，在胎肝中为79.5%和66.4%，在胎肾中为77.9%和77.0%，在LINE 1（p值<0.001）和CCGG含量（p值<0.001）中具有显著的组织特异性DNA甲基化差异。仅使用LINE 1检测，总BPA浓度与胎盘的整体甲基化呈正相关（p值：0.002），表明胎儿暴露后的器官特异性生物学效应。利用敏感的人类临床标本，结果是有益的BPA毒理学和毒理学评估在发育中的人类胎儿。
While urine has been an easily accessible and feasible matrix for human biomonitoring, analytical measurements in internal tissues and organs can provide more accurate exposure assessments to understand disease etiology. This is especially important for the endocrine active compound, bisphenol A (BPA), where studies investigating internal doses at sensitive periods of human development are currently lacking. Herein, BPA concentrations, BPA-specific metabolizing enzyme gene expression, and global DNA methylation were characterized across three matched tissues from elective pregnancy terminations of 2nd trimester human fetuses: the placenta, liver, and kidney (N=12 each; N=36 total). Compared to liver (free: 0.54-50.5 ng/g), BPA concentrations were lower in matched placenta (<0.05-25.4 ng/g) and kidney (0.08-11.1 ng/g) specimens. BPA-specific metabolism gene expression of GUSB, UGT2B15, STS, and SULT1A1 differed across each tissue type; however, conjugation and deconjugation expression patterns were similar across the fetus. Average LINE1 and CCGG global methylation were 58.3 and 59.2% in placenta, 79.5 and 66.4% in fetal liver, and 77.9 and 77.0% in fetal kidney, with significant tissue-specific DNA methylation differences in both LINE1 (p-value <0.001) and CCGG content (p-value <0.001). Total BPA concentrations were positively associated with global methylation for the placenta only using the LINE1 assay (p-value: 0.002), suggesting organ-specific biological effects after fetal exposure. Utilizing sensitive human clinical specimens, results are informative for BPA toxicokinetics and toxicodynamics assessment in the developing human fetus.
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