Document Server@UHasselt >
Research >
Research publications >

Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/26581

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
Citation: 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, tim.nawrot@uhasselt.be
URI: http://hdl.handle.net/1942/26581
DOI: 10.1016/j.envint.2018.02.034
ISI #: 000429877200026
ISSN: 0160-4120
Category: A1
Type: Journal Contribution
Appears in Collections: Research publications

Files in This Item:

Description SizeFormat
Published version1.2 MBAdobe PDF

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.