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Prenatal Ambient Air Pollution, Placental Mitochondrial DNA Content, and Birth Weight in the INMA (Spain) and ENVIRONAGE (Belgium) Birth Cohorts.

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2016-05

Authors

Clemente, Diana B P
Casas, Maribel
Vilahur, Nadia
Begiristain, Haizea
Bustamante, Mariona
Carsin, Anne-Elie
Fernández, Mariana F
Fierens, Frans
Gyselaers, Wilfried
Iñiguez, Carmen

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National Institute of Environmental Health Sciences (NIEHS)
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Abstract

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. CITATION Clemente DB, Casas M, Vilahur N, Begiristain H, Bustamante M, Carsin AE, Fernández MF, Fierens F, Gyselaers W, Iñiguez C, Janssen BG, Lefebvre W, Llop S, Olea N, Pedersen M, Pieters N, Santa Marina L, Souto A, Tardón A, Vanpoucke C, Vrijheid M, Sunyer J, Nawrot TS. 2016. Prenatal ambient air pollution, placental mitochondrial DNA content, and birth weight in the INMA (Spain) and ENVIRONAGE (Belgium) birth cohorts. Environ Health Perspect 124:659-665; http://dx.doi.org/10.1289/ehp.1408981.

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Medical Subject Headings::Health Care::Environment and Public Health::Public Health::Environmental Pollution::Air Pollution
Medical Subject Headings::Geographicals::Geographic Locations::Europe::Belgium
Medical Subject Headings::Phenomena and Processes::Physiological Phenomena::Body Constitution::Body Weights and Measures::Body Size::Body Weight::Birth Weight
Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::DNA::DNA, Circular::DNA, Mitochondrial
Medical Subject Headings::Check Tags::Female
Medical Subject Headings::Phenomena and Processes::Physiological Phenomena::Physiological Processes::Growth and Development::Morphogenesis::Embryonic and Fetal Development::Fetal Development
Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Growth Disorders::Fetal Growth Retardation
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Genes, Mitochondrial
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, Statistical::Linear Models
Medical Subject Headings::Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Organelles::Mitochondria
Medical Subject Headings::Chemicals and Drugs::Inorganic Chemicals::Gases::Nitrogen Oxides::Nitrogen Dioxide
Medical Subject Headings::Anatomy::Embryonic Structures::Placenta
Medical Subject Headings::Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Reproductive Physiological Processes::Reproduction::Pregnancy
Medical Subject Headings::Geographicals::Geographic Locations::Europe::Spain

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Keywords

Contaminación del aire, Bélgica, Peso al nacer, ADN mitocondrial, Femenino, Desarrollo fetal, Retardo del crecimiento fetal, Genes mitocondriales, Modelos Lineales, Mitocondrias, Dióxido de nitrógeno, Placenta, Embarazo, España

Citation

Clemente DB, Casas M, Vilahur N, Begiristain H, Bustamante M, Carsin AE, et al. Prenatal Ambient Air Pollution, Placental Mitochondrial DNA Content, and Birth Weight in the INMA (Spain) and ENVIRONAGE (Belgium) Birth Cohorts. Environ. Health Perspect. 2016; 124(5):659-65