大豆配方奶粉与表观遗传修饰：国际食品和膳食暴露数据库（IFED）研究中女童阴道上皮细胞分析
Soy Formula and Epigenetic Modifications: Analysis of Vaginal Epithelial Cells from Infant Girls in the IFED Study.
作者信息
Harlid Sophia, Adgent Margaret, Jefferson Wendy N, Panduri Vijayalakshmi, Umbach David M, Xu Zongli, Stallings Virginia A, Williams Carmen J, Rogan Walter J, Taylor Jack A
机构信息
Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA.
出版信息
Environ Health Perspect. 2017 Mar;125(3):447-452. doi: 10.1289/EHP428. Epub 2016 Aug 19.
BACKGROUND
Early-life exposure to estrogenic compounds affects the development of the reproductive system in rodent models and humans. Soy products, which contain phytoestrogens such as genistein, are one source of exposure in infants fed soy formula, and they result in high serum concentrations.
OBJECTIVES
Our goal was to determine whether soy exposure is associated with differential DNA methylation in vaginal cells from soy-fed infant girls.
METHODS
Using the Illumina HumanMethylation450 BeadChip, we evaluated epigenome-wide DNA methylation in vaginal cells from four soy formula-fed and six cow formula-fed girls from the Infant Feeding and Early Development (IFED) study. Using pyrosequencing we followed up the two most differentially methylated sites in 214 vaginal cell samples serially collected between birth and 9 months of age from 50 girls (28 soy formula-fed and 22 cow formula-fed). With a mouse model, we examined the effect of neonatal exposure to genistein on gene specific mRNA levels in vaginal tissue.
RESULTS
The epigenome-wide scan suggested differences in methylation between soy formula-fed and cow formula-fed infants at three CpGs in the gene proline rich 5 like () ( < 10). Pyrosequencing of the two feeding groups found that methylation levels progressively diverged with age, with pointwise differences becoming statistically significant after 126 days. Genistein-exposed mice showed a 50% decrease in vaginal mRNA levels compared to controls.
CONCLUSIONS
Girls fed soy formula have altered DNA methylation in vaginal cell DNA which may be associated with decreased expression of an estrogen-responsive gene. Citation: Harlid S, Adgent M, Jefferson WN, Panduri V, Umbach DM, Xu Z, Stallings VA, Williams CJ, Rogan WJ, Taylor JA. 2017. Soy formula and epigenetic modifications: analysis of vaginal epithelial cells from infant girls in the IFED study. Environ Health Perspect 125:447-452; http://dx.doi.org/10.1289/EHP428.
背景
生命早期接触雌激素化合物会影响啮齿动物模型和人类生殖系统的发育。大豆制品含有染料木黄酮等植物雌激素，是食用大豆配方奶粉婴儿的一个接触源，会导致血清浓度升高。
目的
我们的目标是确定大豆接触是否与食用大豆配方奶粉的女婴阴道细胞中DNA甲基化差异有关。
方法
使用Illumina HumanMethylation450 BeadChip，我们评估了来自婴儿喂养与早期发育（IFED）研究的4名食用大豆配方奶粉和6名食用牛奶配方奶粉女孩阴道细胞中的全基因组DNA甲基化情况。使用焦磷酸测序技术，我们对50名女孩（28名食用大豆配方奶粉和22名食用牛奶配方奶粉）出生至9个月期间连续收集的214份阴道细胞样本中两个甲基化差异最大的位点进行了后续研究。利用小鼠模型，我们研究了新生期接触染料木黄酮对阴道组织中基因特异性mRNA水平的影响。
结果
全基因组扫描显示，食用大豆配方奶粉和食用牛奶配方奶粉的婴儿在富含脯氨酸5样蛋白（）基因的三个CpG位点上甲基化存在差异（<10）。对两个喂养组进行焦磷酸测序发现，甲基化水平随年龄增长逐渐分化，126天后逐点差异具有统计学意义。与对照组相比，接触染料木黄酮的小鼠阴道mRNA水平降低了50%。
结论
食用大豆配方奶粉的女孩阴道细胞DNA甲基化发生改变，这可能与雌激素反应基因表达降低有关。引文：Harlid S, Adgent M, Jefferson WN, Panduri V, Umbach DM, Xu Z, Stallings VA, Williams CJ, Rogan WJ, Taylor JA. 2017. 大豆配方奶粉与表观遗传修饰：IFED研究中女婴阴道上皮细胞分析。环境健康展望125:447 - 452；http://dx.doi.org/10.1289/EHP428。
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