Epigenomic Brain & Behavior Lasting Effects Study (PEBBLES) Admin Supplement

胎盘组织通常在出生时就会被丢弃，它是一个分子时间胶囊，可以捕获 基因通过环境相互作用和失调的分子和细胞途径可能 在表观基因组水平上被揭示。确定在出生时反映在 子宫暴露或预测不良神经发育结果是一个重要的目标，它具有 受到现有技术或缺乏相关组织供应的限制。我们目前的团队 儿童环境健康计划中心内跨学科科学家的协作 使用来自前瞻性高危队列研究(弹珠)的现有胎盘样本来确定 出生时宫内暴露多氯联苯的表观遗传生物标志物 三岁时的神经发育结果。在大理石队列中，我们已经证明了 特别是在怀孕的第一个月服用叶酸作为产前维生素的形式 与自闭症风险降低50%有关。我们的人文研究和其他人的工作 也有证据表明，补充叶酸可以对抗表观遗传和 环境污染物对神经发育的影响。此外，使用无偏的整体 基因组亚硫酸氢盐测序(WGBS)，我们先前已经证明胎盘组织 保留着植入前胚胎独特的DNA甲基化模式，因此可以捕获 在非常早期发育的分子状态，这一特征在哺乳动物中是保守的 物种，包括老鼠。建议的多氯联苯表观组脑&行为持久效应研究 (鹅卵石)结合WGBS对高危大理石中的人类胎盘样本进行分析 对胎盘、脑组织和分类细胞进行更广泛的表观基因组分析的队列 从围产期暴露于相同混合物的多氯联苯的小鼠模型衍生的类型 在母亲的弹珠中检测到。要在父母的鹅卵石基金中检验的假设是 围产期接触多氯联苯对神经发育造成不利影响，并留下持久的分子 可在胎盘中检测到的与神经发育相关的基因的签名。这个 在鹅卵石营养补充剂中要检验的假设是饮食中的叶酸 补充剂将防止多氯联苯暴露在 实验动物模型中的表观基因组和人类胎盘。生物信息学和统计学 分析将把基因组数据集与行为和分子结果衡量标准结合起来 并确定在胎盘中是否观察到类似的表观遗传标记 预测人类大脑和行为的长期结果。 好了！

Placental tissue, which is normally discarded at birth, is a molecular time capsule that captures gene by environmental interactions and dysregulated molecular and cellular pathways that can be revealed at the level of the epigenome. Identifying epigenetic biomarkers at birth that reflect in utero exposures or predict adverse neurodevelopmental outcomes is an important goal that has been limited by prior technologies or lack of relevant tissue availability. Our team of currently collaborating interdisciplinary scientists within the Children’s Center for Environmental Health plans to use existing placental samples from a prospective high-risk cohort study (MARBLES) to identify epigenetic biomarkers at birth for in utero exposure to polychlorinated biphenyls (PCBs) and neurodevelopmental outcomes at age three years. In the MARBLES cohort, we have shown that taking folic acid in the form of prenatal vitamins specifically in the first month of pregnancy was associated with a 50% reduction in the risk for autism. Our human studies and the work of others also show evidence that folic acid supplementation can counter epigenetic and neurodevelopmental effects of environmental contaminants. Furthermore, using unbiased whole genome bisulfite sequencing (WGBS), we have previously demonstrated that placental tissues retain the distinctive DNA methylation patterns of the preimplantation embryo and so can capture the molecular state in very early development, a feature that is conserved across mammalian species, including mouse. The proposed PCB Epigenomic Brain & Behavior Lasting Effects Study (PEBBLES) combines WGBS analysis of human placental samples from the high-risk MARBLES cohort with a more extensive epigenomic analysis of placenta and brain tissues and sorted cell types derived from a mouse model of perinatal exposure to the same mixture of PCB congeners detected in MARBLES mothers. The hypothesis to be tested in the parent PEBBLES grant is that perinatal PCB exposures adversely impact neurodevelopment and leave a lasting molecular signature over genes relevant to neurodevelopment that can be detected in placenta. The hypothesis to be tested in the nutritional supplement to PEBBLES is that dietary folic acid supplementation will be protective against the adverse effects of PCB exposures at the level of the epigenome in an experimental animal model and human placenta. Bioinformatic and statistical analyses will integrate the genomic data sets with behavioral and molecular outcome measures and determine whether similar epigenetic marks are observed in placenta that could be used to predict long-lasting brain and behavioral outcomes in humans. !