Maternal paraben exposure during early pregnancy is associated with altered cord blood DNA methylation: The PREDO cohort

IF 10.2 1区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Environment International Pub Date : 2026-04-01 Epub Date: 2026-03-19 DOI:10.1016/j.envint.2026.110195

Marjaana Mäkinen , Johanna Tuhkanen , Marius Lahti-Pulkkinen , Jani Koponen , Hannu Kiviranta , Päivi Ruokojärvi , Darina Czamara , Katri Räikkönen , Jari Lahti

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Abstract

Background

Prenatal exposure to parabens, which are environmental endocrine disrupting chemicals and widely used preservatives in cosmetics, may alter DNA methylation (DNAm) in cord blood.

Study design

In 328 mother–child dyads of the Finnish PREDO Study cohort, we studied with robust linear regression if paraben levels in early pregnancy associated with DNAm levels in cord blood. We measured genome-wide DNAm using Illumina Infinium Human Methylation 450 k or EPIC v1 arrays and concentrations of metabolites of six parabens, namely methyl-, ethyl-, propyl-, isopropyl-, butyl, and isobutylparaben, in early pregnancy urine samples with liquid chromatography – mass spectrometry. All parabens were analyzed as continuous and binary variables (high levels > 66th percentile). As isopropylparaben was present in only 8 % of samples it was analyzed separately as a dichotomic (detected/undetected) variable. Furthermore, we explored the putative functions of associated DNAm markers.

Results

Every mother in the cohort had been exposed to parabens during early pregnancy. After correction for multiple testing there were significant associations (p-value ≤ 2.4 × 10 ^-7) between parabens and hypomethylation of four GpG sites: butylparaben associated with cg19246197 near USP2 (B = -0.009; p = 2.10 × 10^-7), high level of isobutylparaben associated with cg27194164 near GLTD25D1 (B = -0.004; p = 1.89 × 10^-7), detected isopropylparaben associated with cg00973732 in FAM38A (B = 0.007; p = 1.26 × 10^-7), and high levels in the sum of the five most common parabens associated with cg21701043 in chromosome 11 (B = -0.016; p = 1.01 × 10^-7). In total, 52 CpG sites associated with at least one of the parabens at a suggestive level (p-value < 1 × 10⁻⁵). Moreover, butyl- and isobutylparaben showed associations with differentially methylated regions located within PF4 and ABAT.

Conclusions

Paraben exposure during early pregnancy associates with altered DNAm in cord blood.

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妊娠早期母体对羟基苯甲酸酯暴露与脐带血DNA甲基化改变有关：PREDO队列

对羟基苯甲酸酯是一种环境内分泌干扰化学物质，也是化妆品中广泛使用的防腐剂，产前接触对羟基苯甲酸酯可能会改变脐带血中的DNA甲基化（DNAm）。研究设计在芬兰PREDO研究队列的328对母子中，我们用稳健线性回归研究了妊娠早期对羟基苯甲酸酯水平与脐带血中脱氧核糖核酸水平的关系。我们使用Illumina Infinium Human Methylation 450 k或EPIC v1阵列测量了全基因组dna，并使用液相色谱-质谱法测量了妊娠早期尿液样本中六种对羟基苯甲酸酯的代谢物浓度，即甲基-，乙基-，丙基-，异丙基-，丁基和异丁基对羟基苯甲酸酯。所有对羟基苯甲酸酯作为连续变量和二元变量进行分析（高水平 >； 第66百分位）。由于对羟基苯甲酸异丙酯仅存在于8. %的样品中，因此将其作为二分类（检测到/未检测到）变量单独分析。此外，我们还探讨了相关dna标记的推测功能。结果所有母亲在妊娠早期都接触过对羟基苯甲酸酯。修正后的多个测试有显著关联(假设机率 ≤2.4  × 10 7)苯甲酸酯和hypomethylation之间的四个GpG网站:butylparaben与cg19246197 USP2附近(B = -0.009;p = 2.10  × 10 - 7)结果,高水平的相关isobutylparaben cg27194164 GLTD25D1附近(B = -0.004;p = 1.89  × 10 - 7)结果,发现isopropylparaben与cg00973732 FAM38A (B = 0.007;1.26 p =  × 10 - 7),结果和高水平的和相关的五个最常见的防腐剂cg21701043染色体11 (B = -0.016;p = 1.01  × 10 - 7)结果。总共有52个CpG位点与至少一种对羟基苯甲酸酯在提示水平上相关（p值 <； 1 × 10−5）。此外，对羟基苯甲酸丁酯和异丁酯显示与PF4和ABAT内的差异甲基化区域相关。结论妊娠早期接触斯帕拉滨与脐带血dna改变有关。

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来源期刊

Environment International 环境科学-环境科学

CiteScore

21.90

自引率

3.40%

发文量

734

审稿时长

2.8 months

期刊介绍： Environmental Health publishes manuscripts focusing on critical aspects of environmental and occupational medicine, including studies in toxicology and epidemiology, to illuminate the human health implications of exposure to environmental hazards. The journal adopts an open-access model and practices open peer review. It caters to scientists and practitioners across all environmental science domains, directly or indirectly impacting human health and well-being. With a commitment to enhancing the prevention of environmentally-related health risks, Environmental Health serves as a public health journal for the community and scientists engaged in matters of public health significance concerning the environment.