Identifying sensitive windows for prenatal particulate air pollution exposure and mitochondrial DNA content in cord blood

Abstract

Introduction: Changes in mitochondrial DNA (mtDNA) can serve as a marker of cumulative oxidative stress (OS) due to the mitochondria's unique genome and relative lack of repair systems. In utero particulate matter ≤2.5μm (PM2.5) exposure can enhance oxidative stress. Our objective was to identify sensitive windows to predict mtDNA damage experienced in the prenatal period due to PM2.5 exposure using mtDNA content measured in cord blood.

Material and methods: Women affiliated with the Mexican social security system were recruited during pregnancy in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) study. Mothers with cord blood collected at delivery and complete covariate data were included (n=456). Mothers' prenatal daily exposure to PM2.5 was estimated using a satellite-based spatio-temporally resolved prediction model and place of residence during pregnancy. DNA was extracted from umbilical cord leukocytes. Quantitative real-time polymerase chain reaction (qPCR) was used to determine mtDNA content. A distributive lag regression model (DLM) incorporating weekly averages of daily PM2.5 predictions was constructed to plot the association between exposure and OS over the length of pregnancy.

Results: In models that included child's sex, mother's age at delivery, prenatal environmental tobacco smoke exposure, birth year, maternal education, and assay batch, we found significant associations between higher PM2.5 exposure during late pregnancy (35-40weeks) and lower mtDNA content in cord blood.

Conclusions: Increased PM2.5 during a specific prenatal window in the third trimester was associated with decreased mtDNA content suggesting heightened sensitivity to PM-induced OS during this life stage.

Keywords: Distributive lag models; Mitochondrial DNA; Particulate matter; Prenatal exposure.

Copyright © 2016 Elsevier Ltd. All rights reserved.

Figures

Figure 1

Associations between weekly prenatal PM2.5 and mtDNA content in cord blood in the entire sample (n=456). Adjusted for sex, maternal age at delivery, year of birth, maternal education, prenatal exposure to environmental tobacco smoke and batch. The y-axis represents the change in mtDNA content associated with a 10 µg/m3 increase in PM2.5; the x-axis is gestational age in weeks. Solid lines show the predicted change in mtDNA content. Gray areas indicate 95% CIs. A sensitive window is identified for the weeks where the estimated pointwise 95% CI (shaded area) does not include zero.

Figure 2

Sex-stratified associations between weekly prenatal PM2.5 and mtDNA content in cord blood. Adjusted for maternal age at delivery, year of birth, maternal education, prenatal exposure to environmental tobacco smoke and assay batch. The y-axis represents the change in mtDNA content associated with a 10 µg/m3 increase in PM2.5; the x-axis is gestational age in weeks. Solid lines show the predicted change in mtDNA content. Gray areas indicate 95% CIs. A sensitive window is identified for the weeks where the estimated pointwise 95% CI (shaded area) does not include zero

Figure 3

Comparison of linear model estimates for percent difference in mtDNA content per 10 µg/m3 higher PM2.5 concentration averaged over the DLM defined window, the clinically defined trimesters and the entire pregnancy. All models adjusted for child’s sex, maternal age at delivery, maternal education, prenatal exposure to environmental tobacco smoke, year of birth and assay batch.