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Title: Placental circadian pathway methylation and in utero exposure to fine particle air pollution
Authors: Nawrot, Tim S. 
Saenen, Nelly D. 
Schenk, Julie 
Janssen, Bram G. 
Motta, Valeria
Tarantini, Letizia
Cox, Bianca 
Lefebvre, Wouter
Vanpoucke, Charlotte
Maggioni, Cristina
Bollati, Valentina
Issue Date: 2018
Source: ENVIRONMENT INTERNATIONAL, 114, p. 231-241
Abstract: In mammals, a central clock maintains the daily rhythm in accordance with the external environment. At the molecular level, the circadian rhythm is maintained by epigenetic regulation of the Circadian pathway. Here, we tested the role of particulate matter with an aerodynamic diameter <= 2.5 mu m (PM2.5) exposure during gestational life on human placental Circadian pathway methylation, as an important molecular target for healthy development. In 407 newborns, we quantified placental methylation of CpG sites within the promoter regions of the following genes: CLOCK, BMAL1, NPAS2, CRY1-2 and PER1-3 using bisulfite-PCR-pyrosequencing. Daily PM2.5 exposure levels were estimated for each mother's residence, using a spatiotemporal interpolation model. We applied mixed-effects models to study the methylation status of the Circadian pathway genes and in utero PM2.5 exposure, while adjusting for a priori chosen covariates. In a multi-gene model, placental Circadian pathway methylation was positively and significantly (p < 0.0001) associated with 3rd trimester PM2.5 exposure. Consequently, the single-gene models showed relative methylation differences [Log(fold change)] in placental NPAS2 (+0.16; p = 0.001), CRY1 (+0.59; p = 0.0023), PER2 (+0.36; p = 0.0005), and PER3 (+0.42; p = 0.0008) for an IQR increase (8.9 mu g/m(3)) in 3rd trimester PM2.5 exposure. PM2.5 air pollution, an environmental risk factor leading to a pro-inflammatory state of the mother and foetus, is associated with the methylation pattern of genes in the Circadian pathway. The observed alterations in the placental CLOCK epigenetic signature might form a relevant molecular mechanism through which fine particle air pollution exposure might affect placental processes and foetal development.
Notes: Nawrot, TS (reprint author), Ctr Environm Sci, Agoralaan Bldg D, B-3590 Diepenbeek, Belgium,
Keywords: circadian rhythm; placenta; DNA methylation; air pollution; prenatal; CLOCK
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ISSN: 0160-4120
e-ISSN: 1873-6750
DOI: 10.1016/j.envint.2018.02.034
ISI #: 000429877200026
Rights: © 2018 Published by Elsevier Ltd.
Category: A1
Type: Journal Contribution
Validations: ecoom 2019
Appears in Collections:Research publications

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