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. 2022 Mar 14;14(1):40.
doi: 10.1186/s13148-022-01254-2.

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

Juan Aguilera  1 , Xiaorui Han  1 , Shu Cao  1 , John Balmes  2   3 , Fred Lurmann  4 , Tim Tyner  5   6 , Liza Lutzker  2 , Elizabeth Noth  2 , S Katharine Hammond  2 , Vanitha Sampath  1 , Trevor Burt  7 , P J Utz  8 , Purvesh Khatri  9 , Nima Aghaeepour  10 , Holden Maecker  11 , Mary Prunicki  1 , Kari Nadeau  12
Affiliations

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

Juan Aguilera et al. Clin Epigenetics. .

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.

Keywords: Air pollution; DNA methylation; IFNγ; IL10; IL4; Immunology; PM2.5; Pregnancy; Th1; Th2.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Associations between IL4 and ambient air pollutant levels. Q value is the false-discovery-rate-adjusted p-value across all genes, based on linear regression model adjusting for weight, age, season, race, and asthma diagnosis. Q < 0.1 is considered statistically significant. IL4 refers to average DNA methylation across 6 CpG sites in the gene. CO: Carbon monoxide, EC: Elemental carbon, NO2: Nitric dioxide, NOx: Nitric oxides, O3: Ozone, PAH: Polycyclic aromatic hydrocarbons, PM: particulate matter
Fig. 2
Fig. 2
Associations between IL10 and ambient air pollutant levels. Q value is the false-discovery-rate-adjusted p-value across all genes, based on linear regression model adjusting for weight, age, season, race, and asthma diagnosis. Q < 0.1 is considered statistically significant. IL10 refers to average DNA methylation across 4 CpG sites in the gene. CO: Carbon monoxide, EC: Elemental carbon, NO2: Nitric dioxide, NOx: Nitric oxides, O3: Ozone, PAH: Polycyclic aromatic hydrocarbons, PM: particulate matter
Fig. 3
Fig. 3
Associations between IFNγ and ambient air pollutant levels. Q value is the false-discovery-rate-adjusted p-value across all genes, based on linear regression model adjusting for weight, age, season, race, and asthma diagnosis. Q < 0.1 is considered statistically significant. IFNγ refers to average DNA methylation across 3 CpG sites in the gene. CO: Carbon monoxide, EC: Elemental carbon, NO2: Nitric dioxide, NOx: Nitric oxides, O3: Ozone, PAH: Polycyclic aromatic hydrocarbons, PM: particulate matter
Fig. 4
Fig. 4
Associations between Th1 percentage and Ambient Air Pollutant levels. Q value is the false-discovery-rate-adjusted p-value across all genes, based on linear regression model adjusting for weight, age, season, race, and asthma diagnosis. Q < 0.1 is considered statistically significant. CO: Carbon monoxide, EC: Elemental carbon, NO2: Nitric dioxide, NOx: Nitric oxides, O3: Ozone, PAH: Polycyclic aromatic hydrocarbons, PM: particulate matter
Fig. 5
Fig. 5
Associations between Th2 percentage and ambient air pollutant levels. Q value is the false-discovery-rate-adjusted p-value across all genes, based on linear regression model adjusting for weight, age, season, race, and asthma diagnosis. Q < 0.1 is considered statistically significant. CO: Carbon monoxide, EC: Elemental carbon, NO2: Nitric dioxide, NOx: Nitric oxides, O3: Ozone, PAH: Polycyclic aromatic hydrocarbons, PM: particulate matter
Fig. 6
Fig. 6
Associations between Th17 percentage and ambient air pollutant levels. Q value is the false-discovery-rate-adjusted p-value across all genes, based on linear regression model adjusting for weight, age, season, race, and asthma diagnosis. Q < 0.1 is considered statistically significant. CO: Carbon monoxide, EC: Elemental carbon, NO2: Nitric dioxide, NOx: Nitric oxides, O3: Ozone, PAH: Polycyclic aromatic hydrocarbons, PM: particulate matter
Fig. 7
Fig. 7
Associations between each pair of mother’s methylation and baby’s cord blood, at 12 months and 24 months. Bivariate analysis using Pearson’s correlation. False discovery rate adjustment at 0.1 significance level was applied
See this image and copyright information in PMC

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