Sean N. Parker Center for Allergy and Asthma Research, Stanford University, 240 Pasteur, Stanford, CA, 94305, USA.
Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA, USA.
Clin Epigenetics. 2022 Mar 14;14(1):40. doi: 10.1186/s13148-022-01254-2.
Ambient air pollutant (AAP) exposure is associated with adverse pregnancy outcomes, such as preeclampsia, preterm labor, and low birth weight. Previous studies have shown methylation of immune genes associate with exposure to air pollutants in pregnant women, but the cell-mediated response in the context of typical pregnancy cell alterations has not been investigated. Pregnancy causes attenuation in cell-mediated immunity with alterations in the Th1/Th2/Th17/Treg environment, contributing to maternal susceptibility. We recruited women (n = 186) who were 20 weeks pregnant from Fresno, CA, an area with chronically elevated AAP levels. Associations of average pollution concentration estimates for 1 week, 1 month, 3 months, and 6 months prior to blood draw were associated with Th cell subset (Th1, Th2, Th17, and Treg) percentages and methylation of CpG sites (IL4, IL10, IFNγ, and FoxP3). Linear regression models were adjusted for weight, age, season, race, and asthma, using a Q value as the false-discovery-rate-adjusted p-value across all genes.
Short-term and mid-term AAP exposures to fine particulate matter (PM), nitrogen dioxide (NO) carbon monoxide (CO), and polycyclic aromatic hydrocarbons (PAH) were associated with percentages of immune cells. A decrease in Th1 cell percentage was negatively associated with PM (1 mo/3 mo: Q < 0.05), NO (1 mo/3 mo/6 mo: Q < 0.05), and PAH (1 week/1 mo/3 mo: Q < 0.05). Th2 cell percentages were negatively associated with PM (1 week/1 mo/3 mo/6 mo: Q < 0.06), and NO (1 week/1 mo/3 mo/6 mo: Q < 0.06). Th17 cell percentage was negatively associated with NO (3 mo/6 mo: Q < 0.01), CO (1 week/1 mo: Q < 0.1), PM (3 mo/6 mo: Q < 0.05), and PAH (1 mo/3 mo/6 mo: Q < 0.08). Methylation of the IL10 gene was positively associated with CO (1 week/1 mo/3 mo: Q < 0.01), NO (1 mo/3 mo/6 mo: Q < 0.08), PAH (1 week/1 mo/3 mo: Q < 0.01), and PM (3 mo: Q = 0.06) while IL4 gene methylation was positively associated with concentrations of CO (1 week/1 mo/3 mo/6 mo: Q < 0.09). Also, IFNγ gene methylation was positively associated with CO (1 week/1 mo/3 mo: Q < 0.05) and PAH (1 week/1 mo/3 mo: Q < 0.06).
Exposure to several AAPs was negatively associated with T-helper subsets involved in pro-inflammatory and anti-inflammatory responses during pregnancy. Methylation of IL4, IL10, and IFNγ genes with pollution exposure confirms previous research. These results offer insights into the detrimental effects of air pollution during pregnancy, the demand for more epigenetic studies, and mitigation strategies to decrease pollution exposure during pregnancy.
环境空气污染物（AAP）暴露与妊娠不良结局相关，如子痫前期、早产和低出生体重。先前的研究表明，孕妇暴露于空气污染物与免疫基因的甲基化有关，但在典型妊娠细胞改变的背景下，细胞介导的反应尚未得到研究。妊娠导致细胞介导免疫的衰减，Th1/Th2/Th17/Treg 环境发生改变，导致母体易感性增加。我们招募了 186 名来自加利福尼亚州弗雷斯诺的 20 周孕妇，该地区长期存在 AAP 水平升高的情况。血液采集前 1 周、1 个月、3 个月和 6 个月的平均污染浓度估计值与 Th 细胞亚群（Th1、Th2、Th17 和 Treg）百分比和 CpG 位点（IL4、IL10、IFNγ 和 FoxP3）的甲基化相关。线性回归模型调整了体重、年龄、季节、种族和哮喘因素，使用 Q 值作为所有基因的错误发现率调整 p 值。
短期和中期细颗粒物（PM）、二氧化氮（NO）、一氧化碳（CO）和多环芳烃（PAH）的 AAP 暴露与免疫细胞百分比有关。Th1 细胞百分比的降低与 PM（1 个月/3 个月：Q<0.05）、NO（1 个月/3 个月/6 个月：Q<0.05）和 PAH（1 周/1 个月/3 个月：Q<0.05）呈负相关。Th2 细胞百分比与 PM（1 周/1 个月/3 个月/6 个月：Q<0.06）和 NO（1 周/1 个月/3 个月/6 个月：Q<0.06）呈负相关。Th17 细胞百分比与 NO（3 个月/6 个月：Q<0.01）、CO（1 周/1 个月：Q<0.1）、PM（3 个月/6 个月：Q<0.05）和 PAH（1 个月/3 个月/6 个月：Q<0.08）呈负相关。IL10 基因的甲基化与 CO（1 周/1 个月/3 个月：Q<0.01）、NO（1 个月/3 个月/6 个月：Q<0.08）、PAH（1 周/1 个月/3 个月：Q<0.01）和 PM（3 个月：Q=0.06）呈正相关，而 IL4 基因甲基化与 CO（1 周/1 个月/3 个月/6 个月：Q<0.09）呈正相关。此外，IFNγ 基因甲基化与 CO（1 周/1 个月/3 个月：Q<0.05）和 PAH（1 周/1 个月/3 个月：Q<0.06）呈正相关。
几种 AAP 的暴露与妊娠期间参与促炎和抗炎反应的 Th 辅助细胞亚群呈负相关。与污染暴露相关的 IL4、IL10 和 IFNγ 基因的甲基化证实了先前的研究。这些结果提供了对妊娠期间空气污染物有害影响的深入了解，对更多表观遗传学研究的需求，以及减少妊娠期间污染暴露的缓解策略。
