Cited by 223Epigenetics and DNA MethylationAir Quality and Health ImpactsBirth, Development, and Health

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Placental DNA hypomethylation in association with particulate air pollution in early life

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Janssen, Bram G, Godderis, Lode, Pieters, Nicky, Poels, Katrien, Kiciński, Michał, Cuypers, Ann, Fierens, Frans, Penders, Joris, Plusquin, Michelle, Gyselaers, Wilfried, Nawrot, Tim S·2013·Particle and Fibre Toxicology

DOI 10.1186/1743-8977-10-22PMC PMC3686623

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Abstract

BACKGROUND: There is evidence that altered DNA methylation is an important epigenetic mechanism in prenatal programming and that developmental periods are sensitive to environmental stressors. We hypothesized that exposure to fine particles (PM2.5) during pregnancy could influence DNA methylation patterns of the placenta. METHODS: In the ENVIRONAGE birth cohort, levels of 5'-methyl-deoxycytidine (5-mdC) and deoxycytidine (dC) were quantified in placental DNA from 240 newborns. Multiple regression models were used to study placental global DNA methylation and in utero exposure to PM2.5 over various time windows during pregnancy. RESULTS: PM2.5 exposure during pregnancy averaged (25th-75th percentile) 17.4 (15.4-19.3) μg/m3. Placental global DNA methylation was inversely associated with PM2.5 exposures during whole pregnancy and relatively decreased by 2.19% (95% confidence interval [CI]: -3.65, -0.73%, p = 0.004) for each 5 μg/m3 increase in exposure to PM2.5. In a multi-lag model in which all three trimester exposures were fitted as independent variables in the same regression model, only exposure to PM2.5 during trimester 1 was significantly associated with lower global DNA methylation (-2.13% per 5 μg/m3 increase, 95% CI: -3.71, -0.54%, p = 0.009). When we analyzed shorter time windows of exposure within trimester 1, we observed a lower placental DNA methylation at birth during all implantation stages but exposure during the implantation range (6-21d) was strongest associated (-1.08% per 5 μg/m3 increase, 95% CI: -1.80, -0.36%, p = 0.004). CONCLUSIONS: We observed a lower degree of placental global DNA methylation in association with exposure to particulate air pollution in early pregnancy, including the critical stages of implantation. Future studies should elucidate genome-wide and gene-specific methylation patterns in placental tissue that could link particulate exposure during in utero life and early epigenetic modulations.

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Figure 1 Bivariate analysis of placental global DNA methylation in association with prenatal exposure to fine particulate air pollution (PM2.5). PM2.5 exposures (μg/m3) are presented with spearman correlation coefficients for the whole pregnancy (A) and first trimester (B). In panel C, the association between average PM2.5 concentrations and placental global DNA methylation is given. The effect of the average concentrations over 91 days periods was estimated using restricted cubic splines with 5 knots located at the 5th, 25th, 50th, 75th and 95th percentiles.CC BY · PubMed Central

Figure 2 Relative difference in global DNA methylation of placental tissue in association with in utero exposure to particulate air pollution (PM2.5) during various time windows (n = 240). The effect size is a relative difference (95% CI) in mean placental global DNA methylation for each 5 μg/m3 increase of PM2.5 exposure (μg/m3). Model 1 (●) is adjusted for newborn’s gender, maternal age, gestational age, parity, maternal education, smoking status, prenatal acetaminophen use, season at conception and trimester-specific apparent temperature. Model 2 (■) is additionally adjusted for the corresponding NO2 and maximum 8-hour average O3 exposure.CC BY · PubMed Central

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Authors: Janssen, B. G., Godderis, L., Pieters, N., Poels, K., Kiciński, M., Cuypers, A., Fierens, F., Penders, J., Plusquin, M., Gyselaers, W., & Nawrot, T. S.
Affiliations: Hasselt University (BE)
KU Leuven (BE)
Ziekenhuis Oost-Limburg (BE)
Corresponding author: Nawrot, Tim S
ORCID: Janssen, Bram G
Godderis, Lode
Pieters, Nicky
Poels, Katrien
Cuypers, Ann
Penders, Joris
Plusquin, Michelle
Gyselaers, Wilfried
Nawrot, Tim S
Venue: Particle and Fibre Toxicology
Publisher: Springer Science and Business Media LLC
Published: 2013-06-07
Volume: 10
Issue: 1
Pages: 22-22
ISSN: 1743-8977 (ISSN-L)
DOI: 10.1186/1743-8977-10-22
PMC: PMC3686623
OpenAlex: W2143882086
Cited by: 222
References: 70
Citations by year: 2026: 19 · 2025: 7 · 2024: 14 · 2023: 11 · 2022: 25 · 2021: 31 · 2020: 10 · 2019: 22 · 2018: 18 · 2017: 16 · 2016: 19 · 2015: 14 · 2014: 12 · 2013: 3
FWCI: 7.17
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: Particle and Fibre Toxicology (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Document Server@UHasselt (UHasselt) (submittedVersion, cc-by)
Lirias (submittedVersion)
Funders: Fonds Wetenschappelijk Onderzoek
KU Leuven
Universiteit Hasselt
Vlaamse regering
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Air Quality and Health Impacts
Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
Keywords: placental DNA methylation, particulate matter, PM2.5, prenatal air pollution exposure, prenatal programming, epigenetics, implantation, first trimester, placenta, ENVIRONAGE birth cohort, 5-methylcytosine
MeSH terms: Adolescent, Adult, Deoxycytidine, Female, Gestational Age, Humans, Infant, Newborn, Placenta, Pregnancy, Pregnancy Trimesters, Biomarkers, Maternal Exposure, DNA Methylation, Inhalation Exposure, Epigenesis, Genetic, Particulate Matter, Young Adult

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Placental DNA hypomethylation in association with particulate air pollution in early life

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