Merrill Sarah M, Letourneau Nicole, Giesbrecht Gerald F, Edwards Karlie, MacIsaac Julia L, Martin Jonathan W, MacDonald Amy M, Kinniburgh David W, Kobor Michael S, Dewey Deborah, England-Mason Gillian
Department of Psychiatry and Human Behavior, The Warren Alpert Medical School at Brown University, Providence, RI 02903, USA.
Department of Medical Genetics, British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
Epigenomes. 2024 Jan 26;8(1):3. doi: 10.3390/epigenomes8010003.
Di(2-ethylhexyl) phthalate (DEHP) is a common plasticizer that can affect immune system development and susceptibility to infection. Aging processes (measured as epigenetic age acceleration (EAA)) may mediate the immune-related effects of prenatal exposure to DEHP. This study's objective was to examine associations between prenatal DEHP exposure, EAA at three months of age, and the number of upper respiratory infections (URIs) from 12 to 18 months of age using a sample of 69 maternal-child pairs from a Canadian pregnancy cohort. Blood DNA methylation data were generated using the Infinium HumanMethylation450 BeadChip; EAA was estimated using Horvath's pan-tissue clock. Robust regressions examined overall and sex-specific associations. Higher prenatal DEHP exposure ( = 6.52, = 1.22, 11.81) and increased EAA ( = 2.98, = 1.64, 4.32) independently predicted more URIs. In sex-specific analyses, some similar effects were noted for boys, and EAA mediated the association between prenatal DEHP exposure and URIs. In girls, higher prenatal DEHP exposure was associated with decreased EAA, and no mediation was noted. Higher prenatal DEHP exposure may be associated with increased susceptibility to early childhood URIs, particularly in boys, and aging biomarkers such as EAA may be a biological mechanism. Larger cohort studies examining the potential developmental immunotoxicity of phthalates are needed.
邻苯二甲酸二（2-乙基己基）酯（DEHP）是一种常见的增塑剂，会影响免疫系统发育以及感染易感性。衰老过程（以表观遗传年龄加速（EAA）衡量）可能介导产前暴露于DEHP的免疫相关影响。本研究的目的是利用来自加拿大一个妊娠队列的69对母婴样本，检验产前DEHP暴露、3个月大时的EAA以及12至18个月大时上呼吸道感染（URI）次数之间的关联。使用Infinium HumanMethylation450 BeadChip生成血液DNA甲基化数据；使用Horvath的全组织时钟估计EAA。稳健回归分析了总体关联和性别特异性关联。产前DEHP暴露水平较高（β = 6.52，SE = 1.22，95%CI：11.81）以及EAA增加（β = 2.98，SE = 1.64，95%CI：4.32）独立预测了更多的URI。在性别特异性分析中，男孩有一些类似的效应，并且EAA介导了产前DEHP暴露与URI之间的关联。在女孩中，产前DEHP暴露水平较高与EAA降低相关，且未观察到中介作用。产前DEHP暴露水平较高可能与幼儿期URI易感性增加有关，尤其是在男孩中，而诸如EAA等衰老生物标志物可能是一种生物学机制。需要开展更大规模的队列研究来检验邻苯二甲酸酯潜在的发育免疫毒性。
