Increases in Ambient Air Pollutants During Pregnancy Are Linked to Increases in Methylation of IL4, IL10, and IFNγ

Background: 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.

Results: 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).

Conclusion: 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.