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孕期邻苯二甲酸酯暴露与儿童表观遗传年龄加速的关联。

Associations between prenatal phthalate exposure and childhood epigenetic age acceleration.

机构信息

Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA, USA; Center for Computational Biology, University of California, Berkeley, CA, USA.

Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA, USA; Center for Environmental Research and Children's Health (CERCH), School of Public Health, University of California, Berkeley, Berkeley, CA, USA.

出版信息

Environ Res. 2023 Aug 15;231(Pt 1):116067. doi: 10.1016/j.envres.2023.116067. Epub 2023 May 5.

Abstract

BACKGROUND

Phthalates, a group of pervasive endocrine-disrupting chemicals found in plastics and personal care products, have been associated with a wide range of developmental and health outcomes. However, their impact on biomarkers of aging has not been characterized. We tested associations between prenatal exposure to 11 phthalate metabolites on epigenetic aging in children at birth, 7, 9, and 14 years of age. We hypothesized that prenatal phthalate exposure will be associated with epigenetic age acceleration measures at birth and in early childhood, with patterns dependent on sex and timing of DNAm measurement.

METHODS

Among 385 mother-child pairs from the CHAMACOS cohort, we measured DNAm at birth, 7, 9, and 14 years of age, and utilized adjusted linear regression to assess the association between prenatal phthalate exposure and Bohlin's Gestational Age Acceleration (GAA) at birth and Intrinsic Epigenetic Age Acceleration (IEAA) throughout childhood. Additionally, quantile g-computation was utilized to assess the effect of the phthalate mixture on GAA at birth and IEAA throughout childhood.

RESULTS

We found a negative association between prenatal di (2-ethylhexyl) phthalate (DEHP) exposure and IEAA among males at age 7 (-0.62 years; 95% CI:-1.06 to -0.18), and a marginal negative association between the whole phthalate mixture and GAA among males at birth (-1.54 days, 95% CI: -2.79 to -0.28), while most other associations were nonsignificant.

CONCLUSIONS

Our results suggest that prenatal exposure to certain phthalates is associated with epigenetic aging in children. Additionally, our findings suggest that the influence of prenatal exposures on epigenetic age may only manifest during specific periods of child development, and studies relying on DNAm measurements solely from cord blood or single time points may overlook potential relationships.

摘要

背景

邻苯二甲酸酯是一组普遍存在的内分泌干扰化学物质,存在于塑料和个人护理产品中,与广泛的发育和健康结果有关。然而,它们对衰老生物标志物的影响尚未得到描述。我们测试了产前暴露于 11 种邻苯二甲酸酯代谢物与儿童出生时、7 岁、9 岁和 14 岁时的表观遗传衰老之间的关联。我们假设产前邻苯二甲酸酯暴露将与出生时和幼儿期的表观遗传年龄加速测量值相关,其模式取决于性别和 DNAm 测量时间。

方法

在 CHAMACOS 队列的 385 对母婴中,我们在出生时、7 岁、9 岁和 14 岁时测量了 DNAm,并利用调整后的线性回归来评估产前邻苯二甲酸酯暴露与 Bohlin 的妊娠期加速(GAA)之间的关联出生时和整个儿童时期的内在表观遗传年龄加速(IEAA)。此外,还利用定量 g 计算来评估邻苯二甲酸酯混合物对出生时 GAA 和整个儿童时期 IEAA 的影响。

结果

我们发现,产前二(2-乙基己基)邻苯二甲酸酯(DEHP)暴露与男性 7 岁时的 IEAA 呈负相关(-0.62 岁;95%CI:-1.06 至-0.18),而整个邻苯二甲酸酯混合物与男性出生时的 GAA 呈边际负相关(-1.54 天,95%CI:-2.79 至-0.28),而大多数其他关联则无统计学意义。

结论

我们的结果表明,产前接触某些邻苯二甲酸酯与儿童的表观遗传衰老有关。此外,我们的研究结果表明,产前暴露对表观遗传年龄的影响可能仅在儿童发育的特定时期表现出来,并且仅依赖于脐带血或单个时间点的 DNAm 测量的研究可能会忽略潜在的关系。

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