产前颗粒物空气污染暴露与脐带血端粒长度的关联:胎儿性别对其的修饰作用。
Association between prenatal particulate air pollution exposure and telomere length in cord blood: Effect modification by fetal sex.
机构信息
Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY, USA.
出版信息
Environ Res. 2019 May;172:495-501. doi: 10.1016/j.envres.2019.03.003. Epub 2019 Mar 2.
INTRODUCTION
In utero particulate matter exposure produces oxidative stress that impacts cellular processes that include telomere biology. Newborn telomere length is likely critical to an individual's telomere biology; reduction in this initial telomere setting may signal increased susceptibility to adverse outcomes later in life. We examined associations between prenatal particulate matter with diameter ≤2.5 µm (PM) and relative leukocyte telomere length (LTL) measured in cord blood using a data-driven approach to characterize sensitive windows of prenatal PM effects and explore sex differences.
METHODS
Women who were residents of Mexico City and affiliated with the Mexican Social Security System were recruited during pregnancy (n = 423 for analyses). Mothers' prenatal exposure to PM was estimated based on residence during pregnancy using a validated satellite-based spatio-temporally resolved prediction model. Leukocyte DNA was extracted from cord blood obtained at delivery. Duplex quantitative polymerase chain reaction was used to compare the relative amplification of the telomere repeat copy number to single gene (albumin) copy number. A distributed lag model incorporating weekly averages for PM over gestation was used in order to explore sensitive windows. Sex-specific associations were examined using Bayesian distributed lag interaction models.
RESULTS
In models that included child's sex, mother's age at delivery, prenatal environmental tobacco smoke exposure, pre-pregnancy BMI, gestational age, birth season and assay batch, we found significant associations between higher PM exposure during early pregnancy (4-9 weeks) and shorter LTL in cord blood. We also identified two more windows at 14-19 and 34-36 weeks in which increased PM exposure was associated with longer LTL. In stratified analyses, the mean and cumulative associations between PM and shortened LTL were stronger in girls when compared to boys.
CONCLUSIONS
Increased PM during specific prenatal windows was associated with shorter LTL and longer LTL. PM was more strongly associated with shortened LTL in girls when compared to boys. Understanding sex and temporal differences in response to air pollution may provide unique insight into mechanisms.
引言
宫内颗粒物暴露会产生氧化应激,影响包括端粒生物学在内的细胞过程。新生儿端粒长度可能对个体的端粒生物学至关重要;这种初始端粒设定的减少可能表明个体在以后的生活中更容易受到不良后果的影响。我们使用数据驱动的方法来研究产前直径≤2.5 µm 的颗粒物 (PM) 与脐带血中相对白细胞端粒长度 (LTL) 之间的关联,以描述产前 PM 影响的敏感窗口,并探讨性别差异。
方法
在怀孕期间,我们招募了居住在墨西哥城并隶属于墨西哥社会保险系统的女性(n=423 用于分析)。根据怀孕期间的居住地,使用经过验证的基于卫星的时空分辨率预测模型来估计母亲的产前 PM 暴露情况。在分娩时从脐带血中提取白细胞 DNA。使用双定量聚合酶链反应比较端粒重复序列拷贝数与单个基因(白蛋白)拷贝数的相对扩增。为了探索敏感窗口,我们使用了一个包含整个妊娠期每周平均 PM 的分布式滞后模型。使用贝叶斯分布式滞后相互作用模型检查性别特异性关联。
结果
在包括孩子性别、母亲分娩时的年龄、产前环境烟草烟雾暴露、孕前 BMI、胎龄、出生季节和检测批次在内的模型中,我们发现早期妊娠(4-9 周)期间 PM 暴露水平较高与脐带血中 LTL 较短之间存在显著关联。我们还发现了另外两个窗口,即 14-19 周和 34-36 周,在此期间,PM 暴露增加与 LTL 延长相关。在分层分析中,与男孩相比,女孩 PM 与缩短 LTL 的平均和累积关联更强。
结论
特定产前窗口期内 PM 增加与 LTL 缩短和 LTL 延长有关。与男孩相比,PM 与女孩缩短 LTL 的关联更强。了解对空气污染的性别和时间差异反应可能会提供对机制的独特见解。