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Archives of Public Health

Volume 73 Supplement 1

Methods in Epidemiology Symposium

Open Access

Placental DNA methylation as a proxy for fetal neurodevelopment and sex-specific associations with in utero particulate air pollution

  • Nelly Saenen1,
  • Bram Janssen1,
  • Karen Vrijens1,
  • Harry Roels1,
  • Wim Vanden Berghe2,
  • Wilfried Gyselaers3,
  • Charlotte Vanpoucke4,
  • Patrick De Boever5 and
  • Tim Nawrot1
Archives of Public HealthThe official journal of the Belgian Public Health Association201573(Suppl 1):P35

Published: 17 September 2015

Background and aims

Exposure to particulate matter (PM) air pollution during pregnancy may affect human fetal development. Epigenetic mechanisms are believed to play an essential role in the developmental changes during early life. Within the ENVIRONAGE birth cohort, we investigated whether in utero exposure to PM is associated with differences in placental DNA methylation of genes involved in early neurodevelopment, i.e., Brain-Derived Neurotrophic Factor (BDNF), Leptin (LEP) and 5-Hydroxytryptamine (serotonin) receptor 2A (HTR2A).


Using highly quantitative bisulfite-PCR pyrosequencing, DNA promoter methylation was assessed in placental tissue of 385 newborns from the ENVIRONAGE birth cohort. Daily PM2.5 exposure levels were estimated for each participant's home address using a spatiotemporal interpolation model in combination with a dispersion model. We fitted mixed-effect models, stratified for newborn's sex, to evaluate the associations between DNA promoter methylation of the selected genes and PM2.5 exposure during pregnancy.


Methylation of placental BDNF in male infants rose by 0.46% (p = 0.02) for an interquartile range (IQR) increment in PM2.5 during the second trimester of pregnancy. For placental HTR2A, methylation in male infants rose by 4.8% (p = 0.02) for an IQR increment in first trimester PM2.5 exposure. These associations were independent of maternal age, maternal education, maternal smoking status, gestational age, CpG site, first trimester temperature, and season at birth. No associations were observed between PM2.5 exposure and placental LEP methylation. In girls no significant associations were noted.


Placental promoter methylation of BDNF and HTR2A, two genes implicated in early neurodevelopmental trajectories, are influenced by in utero exposure to PM2.5 in a sex-specific way. Future studies should elucidate the significance of the sex-specific PM2.5 impact on placental promoter methylation with respect to neurodevelopment later in life.

Authors’ Affiliations

Hasselt University, Diepenbeek, Belgium
Department of Biomedical Sciences, PPES Epigenetic Signaling Lab, University of Antwerp, Antwerp, Belgium
Department of Obstetrics, East-Limburg Hospital, Genk, Belgium
Belgian Interregional Environment Agency, Brussels, Belgium
Flemish Institute for Technological Research (VITO), Mol, Belgium


© Saenen et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.


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