Increases in ambient air pollutants during pregnancy are linked to increases in methylation of IL4, IL10, and IFNγ

Abstract

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 (PM2.5), nitrogen dioxide (NO2) carbon monoxide (CO), and polycyclic aromatic hydrocarbons (PAH456) were associated with percentages of immune cells. A decrease in Th1 cell percentage was negatively associated with PM2.5 (1 mo/3 mo: Q < 0.05), NO2 (1 mo/3 mo/6 mo: Q < 0.05), and PAH456 (1 week/1 mo/3 mo: Q < 0.05). Th2 cell percentages were negatively associated with PM2.5 (1 week/1 mo/3 mo/6 mo: Q < 0.06), and NO2 (1 week/1 mo/3 mo/6 mo: Q < 0.06). Th17 cell percentage was negatively associated with NO2 (3 mo/6 mo: Q < 0.01), CO (1 week/1 mo: Q < 0.1), PM2.5 (3 mo/6 mo: Q < 0.05), and PAH456 (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), NO2 (1 mo/3 mo/6 mo: Q < 0.08), PAH456 (1 week/1 mo/3 mo: Q < 0.01), and PM2.5 (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 PAH456 (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.

Epigenome-wide association of neonatal methylation and trimester-specific prenatal PM2.5 exposure

“…50 Although it is unclear whether this hypermethylation is mechanistically responsible for PM 2.5 -induced inflammation, the observed association between increased PM 2.5 exposure and cg18705808 DNAm is consistent with previously established links between PM 2.5 and inflammation. 2,51,52 The observation that IPA produced different results when given top CpG sites from different periods could suggest that PM 2.5 exposure during pregnancy has unique downstream physiological effects depending on the timing of exposure. A different set of pathways and networks were associated with trimester 1 PM 2.5 exposure compared with trimester 2.…”

“…50 Although it is unclear whether this hypermethylation is mechanistically responsible for PM 2.5 -induced inflammation, the observed association between increased PM 2.5 exposure and cg18705808 DNAm is consistent with previously established links between PM 2.5 and inflammation. 2,51,52…”

Granzymes, IL-16, and poly(ADP-ribose) polymerase 1 increase during wildfire smoke exposure

“…11 Also, our group previously published data showing increases in immune biomarkers and DNA methylation of immunoregulatory genes during wildfire smoke exposure. [12][13][14] In this study, we assessed the impact of wildfire smoke exposure on the immune system (determined by highthroughput proteomics and immune cell phenotyping) before and during exposure to wildfire smoke. Furthermore, we explored possible associations with epithelial barrier disruption by quantifying zonulin, which plays an important pathogenic role in a variety of diseases by regulating tight junctions, 15 which have been correlated with inflammatory pathways.…”

Prenatal exposure to particulate matter and term low birth weight: systematic review and meta-analysis

“…More recent studies indicate that air pollutants (carbon nanoparticles) inhaled by pregnant women can cross the placenta and enter multiple organs such as the lungs, liver, and brain of the fetus (Bongaerts et al 2022 ). Epigenetic marks of gestational PM exposure discovered in the placenta and cord blood, such as DNA methylation, histone H3 modifications, and telomere length, may also play an important role (Aguilera et al 2022 ; Zhao et al 2021 ; Zheng et al 2017 ; Martens et al 2017 ).…”