Background: Mitochondria are sensitive to environmental toxicants due to their lack of repair capacity. Changes in mitochondrial DNA (mtDNA) content may represent a biologically relevant intermediate outcome in mechanisms linking air pollution and fetal growth restriction.
Objective: We investigated whether placental mtDNA content is a possible mediator of the association between prenatal nitrogen dioxide (NO2) exposure and birth weight.
Methods: We used data from two independent European cohorts: INMA (n = 376; Spain) and ENVIRONAGE (n = 550; Belgium). Relative placental mtDNA content was determined as the ratio of two mitochondrial genes (MT-ND1 and MTF3212/R3319) to two control genes (RPLP0 and ACTB). Effect estimates for individual cohorts and the pooled data set were calculated using multiple linear regression and mixed models. We also performed a mediation analysis.
Results: Pooled estimates indicated that a 10-μg/m3 increment in average NO2 exposure during pregnancy was associated with a 4.9% decrease in placental mtDNA content (95% CI: –9.3, –0.3%) and a 48-g decrease (95% CI: –87, –9 g) in birth weight. However, the association with birth weight was significant for INMA (–66 g; 95% CI: –111, –23 g) but not for ENVIRONAGE (–20 g; 95% CI: –101, 62 g). Placental mtDNA content was associated with significantly higher mean birth weight (pooled analysis, interquartile range increase: 140 g; 95% CI: 43, 237 g). Mediation analysis estimates, which were derived for the INMA cohort only, suggested that 10% (95% CI: 6.6, 13.0 g) of the association between prenatal NO2 and birth weight was mediated by changes in placental mtDNA content.
Conclusion: Our results suggest that mtDNA content can be one of the potential mediators of the association between prenatal air pollution exposure and birth weight.
1Center for Environmental Sciences, Hasselt University, Diepenbeek, Belgium; 2Center for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; 3CIBER de Epidemiología y Salud Pública (CIBERESP), Institute of Health Carlos III, Madrid, Spain; 4Institute for environmental medicine (IMM), Karolinska Institutet, Sweden; 5Health Research Institute (BIODONOSTIA), Gipuzkoa, Spain; 6Universitat Pompeu Fabra, Barcelona, Spain; 7Center for Genomic Regulation (CRG), Barcelona, Spain; 8Department of Radiology, University of Granada, Granada, Spain; 9Instituto de Investigación Biosanitaria de Granada, ibs.GRANADA, Hospital Universitario San Cecilio, Granada, Spain; 10Belgian Interregional Environment Agency, Brussels, Belgium; 11Department of Obstetrics, East-Limburg Hospital, Genk, Belgium; 12Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain; 13University of Valencia, Valencia, Spain; 14Flemish Institute for Technological Research (VITO), Mol, Belgium; 15INSERM (National Institute of Health and Medical Research), U823, Team of Environmental Epidemiology Applied to Reproduction and Respiratory Health, Institute Albert Bonniot, Grenoble, France; 16Molecular Epidemiology of Cancer Unit, University Institute of Oncology, University of Oviedo, Oviedo, Spain; 17IMIM (Hospital del Mar Research Institute), Barcelona, Spain; 18Department of Public Health & Primary Care, Unit Environment & Health, Leuven University, Leuven, Belgium
Recommended Citation:
Diana B.P. Clemente,1,2 Maribel Casas,et al. Prenatal Ambient Air Pollution, Placental Mitochondrial DNA Content, and Birth Weight in the INMA (Spain) and ENVIRONAGE (Belgium) Birth Cohorts[J]. Environmental Health Perspectives,2016-01-01,Volume 124(Issue 5):659