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孕期邻苯二甲酸酯暴露、出生结局与 Alu 和 LINE-1 重复元件的 DNA 甲基化:中国的一项初步研究。

Prenatal phthalate exposure, birth outcomes and DNA methylation of Alu and LINE-1 repetitive elements: A pilot study in China.

机构信息

Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.

Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, WuHan, PR China; Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.

出版信息

Chemosphere. 2018 Sep;206:759-765. doi: 10.1016/j.chemosphere.2018.05.030. Epub 2018 May 7.

Abstract

BACKGROUND

Epigenetic mechanisms, such as altered DNA methylation, may participate in the relationship between prenatal phthalate exposure and adverse birth outcomes.

OBJECTIVE

To explore the mediation effect of DNA methylation in the associations of phthalate exposure before delivery with birth outcomes in a Chinese cohort.

METHODS

Eight phthalate metabolites in maternal urine before delivery and DNA methylation of Alu and long interspersed nucleotide elements (LINE-1) in cord blood were determined among 106 mother-infant pairs. General additive models were used to assess the associations of maternal urinary phthalate metabolites with birth outcomes and DNA methylation; the mediating role of DNA methylation in cord blood was evaluated by mediation analysis.

RESULTS

We found sex-specific associations between prenatal phthalate exposure and birth outcomes and DNA methylation of cord blood. For example, the molar sum of di-2-(ethylhexyl) phthalate (∑DEHPm) metabolites in maternal urine was positively associated with gestational age among male newborns only (P < 0.05); maternal urinary monobenzyl phthalate (MBzP) was negatively associated with Alu methylation among female newborns only (P < 0.05). Mediation analysis did not find that methylation of Alu and LINE-1 to be a direct mediator in the relationships between maternal urinary phthalate metabolites before delivery and birth outcomes.

CONCLUSION

Prenatal exposure to certain phthalates was associated with altered birth outcomes and decreased repetitive element methylation of newborns. However, the altered birth outcomes exerted by prenatal phthalate exposure does not seem to be directly mediated through repetitive element methylation in cord blood.

摘要

背景

表观遗传机制,如 DNA 甲基化改变,可能参与了产前邻苯二甲酸酯暴露与不良出生结局之间的关系。

目的

探索 DNA 甲基化在产前邻苯二甲酸酯暴露与中国队列新生儿出生结局之间的关联中的中介作用。

方法

在 106 对母婴中,测定了分娩前母体尿液中 8 种邻苯二甲酸酯代谢物和脐带血中 Alu 和长散布核元件(LINE-1)的 DNA 甲基化。使用广义加性模型评估母体尿液邻苯二甲酸酯代谢物与出生结局和脐带血 DNA 甲基化的关联;通过中介分析评估脐带血中 DNA 甲基化的中介作用。

结果

我们发现产前邻苯二甲酸酯暴露与出生结局和脐带血 DNA 甲基化之间存在性别特异性关联。例如,母体尿液中二-(2-乙基己基)邻苯二甲酸酯(∑DEHPm)代谢物的摩尔总和仅与男婴的胎龄呈正相关(P<0.05);母体尿液中单苄基邻苯二甲酸酯(MBzP)仅与女婴的 Alu 甲基化呈负相关(P<0.05)。中介分析并未发现,产前尿液邻苯二甲酸酯代谢物与出生结局之间的关系中,Alu 和 LINE-1 的甲基化是直接的中介因素。

结论

产前接触某些邻苯二甲酸酯与新生儿出生结局改变和重复元件甲基化减少有关。然而,产前邻苯二甲酸酯暴露对出生结局的改变似乎并不是通过脐带血中重复元件甲基化直接介导的。

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