title: Mitochondrial oxidative DNA damage and exposure to particulate air pollution in mother-newborn pairs.
abstract: BACKGROUND
  Studies emphasize the importance of particulate matter (PM) in the formation of reactive oxygen species and inflammation. We hypothesized that PM exposure during different time windows in pregnancy influences mitochondrial 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, which is an established biomarker for oxidative stress, in both maternal and foetal blood.
  
  
  METHODS
  We investigated maternal (n = 224) and cord blood (n = 293) from mother-newborn pairs that were enrolled in the ENVIRONAGE birth cohort. We determined mitochondrial 8-OHdG by quantitative polymerase chain reaction (qPCR). Multivariable regression models were used to assess the association between mitochondrial 8-OHdG with PM10 and PM2.5 exposure over various time windows during pregnancy.
  
  
  RESULTS
  In multivariable analysis, PM10 exposure during the entire pregnancy was positively associated with levels of mitochondrial 8-OHdG in maternal blood. For an IQR increment in PM10 exposure an increase of 18.3 % (95 % confidence interval (CI): 5.6 to 33.4 %, p = 0.004) in 8-OHdG was observed. PM10 exposure during the last trimester of pregnancy was positively associated with levels of 8-OHdG (28.1, 95 % CI: 8.6 to 51.2 %, p = 0.004, for an IQR increment in PM10). In a similar way, PM2.5 exposure was significantly associated with an increase of mitochondrial 8-OHdG levels in maternal blood during the entire pregnancy (13.9, 95 % CI: 0.4 to 29.4 %, p = 0.04 for an IQR increment in PM2.5 exposure) and third trimester of pregnancy (28.1, 95 % CI: 3.6 to 58.4 %, p = 0.02 for an IQR increment in PM2.5 exposure). In umbilical cord blood, 8-OHdG levels were significantly associated with PM10 exposure during first and second trimester of pregnancy with respectively an increase of 23.0 % (95 % CI: 5.9 to 42.8 %, p = 0.007) and 16.6 % (95 % CI: 1.8 to 33.5 %, p = 0.03) for an IQR increment in PM10 exposure.
  
  
  CONCLUSIONS
  We found PM-associated increased mitochondrial oxidative DNA damage during pregnancy in both mothers and their newborns. Accordingly, our study showed that particulate air pollution exposure in early life plays a role in increasing systemic oxidative stress, at the level of the mitochondria, both in mother and foetus.
authors.affiliation: EPIGET-Epidemiology, Epigenetics and Toxicology Lab-Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy. lotte.grevendonk@unimi.it.
authors.forename: Lotte
authors.initials: L
authors.lastname: Grevendonk
authors.affiliation: Centre for Environmental Sciences, Hasselt University, Hasselt, Belgium. bram.janssen@uhasselt.be.
authors.forename: Bram G
authors.initials: BG
authors.lastname: Janssen
authors.affiliation: Belgian Interregional Environment Agency, Brussels, Belgium. vanpoucke@irceline.be.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Vanpoucke
authors.affiliation: Flemish Institute for Technological Research (VITO), Mol, Belgium. wouter.lefebvre@vito.be.
authors.forename: Wouter
authors.initials: W
authors.lastname: Lefebvre
authors.affiliation: EPIGET-Epidemiology, Epigenetics and Toxicology Lab-Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy. mirjam.hoxha@unimi.it.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Hoxha
authors.affiliation: EPIGET-Epidemiology, Epigenetics and Toxicology Lab-Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy. valentina.bollati@unimi.it.
authors.forename: Valentina
authors.initials: V
authors.lastname: Bollati
authors.affiliation: Centre for Environmental Sciences, Hasselt University, Hasselt, Belgium. tim.nawrot@uhasselt.be.|Department of Public Health & Primary Care, Occupational and Environmental Medicine, Leuven University, Leuven, Belgium. tim.nawrot@uhasselt.be.
authors.forename: Tim S
authors.initials: TS
authors.lastname: Nawrot
mesh_terms: D000328:Adult; D000393:Air Pollutants / Q000633:toxicity*; D015331:Cohort Studies; D004272:DNA, Mitochondrial / Q000097:blood*; D004781:Environmental Exposure / Q000706:statistics & numerical data; D005260:Female; D005312:Fetal Blood / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D018811:Maternal Exposure / Q000706:statistics & numerical data; D052638:Particulate Matter / Q000633:toxicity*; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D055815:Young Adult
chemical_list: D000393:Air Pollutants; D004272:DNA, Mitochondrial; D052638:Particulate Matter