title: Placental DNA hypomethylation in association with particulate air pollution in early life.
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.
authors.forename: Bram G
authors.initials: BG
authors.lastname: Janssen
authors.forename: Lode
authors.initials: L
authors.lastname: Godderis
authors.forename: Nicky
authors.initials: N
authors.lastname: Pieters
authors.forename: Katrien
authors.initials: K
authors.lastname: Poels
authors.forename: Michał
authors.initials: M
authors.lastname: Kiciński
authors.forename: Ann
authors.initials: A
authors.lastname: Cuypers
authors.forename: Frans
authors.initials: F
authors.lastname: Fierens
authors.forename: Joris
authors.initials: J
authors.lastname: Penders
authors.forename: Michelle
authors.initials: M
authors.lastname: Plusquin
authors.forename: Wilfried
authors.initials: W
authors.lastname: Gyselaers
authors.forename: Tim S
authors.initials: TS
authors.lastname: Nawrot
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000187:drug effects; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D019570:Inhalation Exposure / Q000009:adverse effects*; D018811:Maternal Exposure / Q000009:adverse effects*; D052638:Particulate Matter / Q000009:adverse effects*; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D011264:Pregnancy Trimesters / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D052638:Particulate Matter; D003841:Deoxycytidine; C016569:5-methyldeoxycytidine