Newborn sex-specific transcriptome signatures and gestational exposure to fine particles: findings from the ENVIRONAGE birth cohortReport as inadecuate

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Environmental Health

, 16:52

Environmental Epidemiology


BackgroundAir pollution exposure during pregnancy has been associated with adverse birth outcomes and health problems later in life. We investigated sex-specific transcriptomic responses to gestational long- and short-term exposure to particulate matter with a diameter < 2.5 μm PM2.5 in order to elucidate potential underlying mechanisms of action.

MethodsWhole genome gene expression was investigated in cord blood of 142 mother-newborn pairs that were enrolled in the ENVIRONAGE birth cohort. Daily PM2.5 exposure levels were calculated for each mother’s home address using a spatial-temporal interpolation model in combination with a dispersion model to estimate both long- annual average before delivery and short- last month of pregnancy term exposure. We explored the association between gene expression levels and PM2.5 exposure, and identified modulated pathways by overrepresentation analysis and gene set enrichment analysis.

ResultsSome processes were altered in both sexes for long- e.g. DNA damage or short-term exposure e.g. olfactory signaling. For long-term exposure in boys neurodevelopment and RhoA pathways were modulated, while in girls defensin expression was down-regulated. For short-term exposure we identified pathways related to synaptic transmission and mitochondrial function boys and immune response girls.

ConclusionsThis is the first whole genome gene expression study in cord blood to identify sex-specific pathways altered by PM2.5. The identified transcriptome pathways could provide new molecular insights as to the interaction pattern of early life PM2.5 exposure with the biological development of the fetus.

KeywordsAmbient air pollution Particulate matter Microarray analysis Fetal Sex AbbreviationsBMIbody mass index

EnvironageENVIRonmental influence ON early AGEing

FDRfalse discovery rate

GOgene ontology

GSEAGene Set Enrichment Analysis

IFDMImmission Frequency Distribution Model

ORAoverrepresentation analysis

PAHpolycyclic aromatic hydrocarbons

PMparticulate matter

PM2.5particulate matter with a diameter < 2.5 μm

Rpartial correlation coefficients

ROSreactive oxygen species

SAsensitivity analysis

SDstandard deviation

TCAtricarboxylic acid

WBCwhite blood cell

Electronic supplementary materialThe online version of this article doi:10.1186-s12940-017-0264-y contains supplementary material, which is available to authorized users.

Author: Ellen Winckelmans - Karen Vrijens - Maria Tsamou - Bram G. Janssen - Nelly D. Saenen - Harry A. Roels - Jos Kleinjans -


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