产前氯吡硫磷暴露与 PPARγ H3K4me3 和 DNA 甲基化水平及儿童发育的关系。
Prenatal chlorpyrifos exposure in association with PPARγ H3K4me3 and DNA methylation levels and child development.
机构信息
Institute of Environmental and Occupational Health Sciences, College of Public Health, National Taiwan University, Taipei, 100, Taiwan.
Department of Pediatrics, National Taiwan University College of Medicine and Hospital, Taipei, 100, Taiwan; Department of Pediatrics, Cathay General Hospital, Taipei, 100, Taiwan.
出版信息
Environ Pollut. 2021 Apr 1;274:116511. doi: 10.1016/j.envpol.2021.116511. Epub 2021 Jan 16.
BACKGROUND
Chlorpyrifos, one of the most widely used pesticides, can penetrate the placenta and affect fetal growth and neurodevelopment. Epigenetic regulation of peroxisome proliferator-activated receptor gamma (PPARγ), such as DNA methylation and trimethylation of lysine 4 of H3 (H3K4me3), may provide a potential mechanism for how fetal growth and development are impacted by chlorpyrifos exposure. The aims of the study were to investigate whether prenatal chlorpyrifos exposure was associated with H3K4me3 and DNA methylation levels of the PPARγ gene in the placenta and the related effects on birth outcomes and neurodevelopment.
METHODS
Among 425 mother-infant pairs from the Taiwan Birth Panel Study, chlorpyrifos levels were measured in cord blood by using online SPE-LC/HESI/MS/MS; placental PPARγ H3K4me3 and DNA methylation levels were measured by ChIP-qPCR and pyrosequencing, respectively; the neonates' health outcomes were extracted from the medical records; and childhood neurodevelopment was evaluated by using the Comprehensive Developmental Inventory for Infants and Toddlers in 2-year-old children. Multivariable regression models were used to adjust for potential confounders.
RESULTS
After controlling for potential confounders, each unit increase in the natural log-transformed prenatal chlorpyrifos exposure level was associated with an increase in the PPARγ DNA methylation level (adjusted β (aβ) = 0.77, p = 0.032) and poorer performance in the cognitive and language domains at 2 years old, especially in boys (aβ = -1.66, p = 0.016, and aβ = -1.79, p = 0.023, respectively). PPARγ H3K4me3 levels were positively associated with gestational age (aβ = 0.16, p = 0.011), birth weight (aβ = 30.52, p = 0.013), birth length (aβ = 0.18, p = 0.003 and aβ = 0.15, p = 0.042), and gross-motor performance (aβ = 1.67, p = 0.036).
CONCLUSIONS
Our findings suggested that prenatal chlorpyrifos exposure affected PPARγ DNA methylation levels and performance in the cognitive and language domains.
背景
毒死蜱是使用最广泛的杀虫剂之一，它可以穿透胎盘并影响胎儿的生长和神经发育。过氧化物酶体增殖物激活受体 γ（PPARγ）的表观遗传调控，如 DNA 甲基化和组蛋白 H3 赖氨酸 4 的三甲基化（H3K4me3），可能为胎儿生长和发育受毒死蜱暴露影响提供了潜在机制。本研究的目的是探讨产前接触毒死蜱是否与胎盘 PPARγ 基因的 H3K4me3 和 DNA 甲基化水平有关，以及这些变化对出生结局和神经发育的相关影响。
方法
在来自台湾出生队列研究的 425 对母婴中，通过在线 SPE-LC/HESI/MS/MS 在脐血中测量毒死蜱水平；通过 ChIP-qPCR 和焦磷酸测序分别测量胎盘 PPARγ H3K4me3 和 DNA 甲基化水平；从病历中提取新生儿健康结局数据；并在 2 岁儿童中使用婴幼儿综合发育量表评估儿童期神经发育情况。多变量回归模型用于调整潜在的混杂因素。
结果
在控制潜在混杂因素后，产前毒死蜱暴露水平的自然对数每增加一个单位，与 PPARγ DNA 甲基化水平的升高相关（调整后的β（aβ）= 0.77，p = 0.032），并且 2 岁时认知和语言领域的表现更差，尤其是男孩（aβ = -1.66，p = 0.016 和 aβ = -1.79，p = 0.023）。PPARγ H3K4me3 水平与胎龄（aβ = 0.16，p = 0.011）、出生体重（aβ = 30.52，p = 0.013）、出生长度（aβ = 0.18，p = 0.003 和 aβ = 0.15，p = 0.042）和粗大运动表现（aβ = 1.67，p = 0.036）呈正相关。
结论
我们的研究结果表明，产前接触毒死蜱会影响 PPARγ DNA 甲基化水平以及认知和语言领域的表现。
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