Association of particulate air pollution during pregnancy and mitochondrial DNA damage exemplified by 8-OHdG

Abstract

BACKGROUND: 8OHdG is an established biomarker for oxidative stress. Several studies emphasize the effect of particulate matter (PM) on 8OHdG. In addition, a growing body of evidence indicates influence of PM on mitochondrial DNA content (mtDNA), a marker for mitochondrial stress. We hypothesized that PM exposure during pregnancy results in an increase in mitochondrial 8OHdG levels and will lead to a change in mtDNA content in maternal. OBJECTIVES: We examined 8OHdG and mtDNA content in association with in utero PM10 exposure. With mediation analysis we investigated intermediate mechanisms of 8OHdG on association of PM10 and mtDNA content METHODS: We investigated maternal and cord blood from 224 mother-newborn pairs that were enrolled in the ENVIRONAGE birth cohort. We determined mitochondrial 8OHdG and mtDNA content by qPCR. RESULTS: PM10 exposure during entire pregnancy was positively associated with mitochondrial 8OHdG in maternal blood. For each IQR increment of PM10 an increase of 23% (95% confidence CI: 8.4, 39.6 p = 0.002) in 8OHdG was observed. PM10 during last trimester of pregnancy was positively associated with levels of 8OHdG (14%, 95% CI: 3.3, 28.5 p = 0.01, for each IQR increment of PM10), and with of mtDNA content; (29.6%, 95% CI: 10.9, 51.4, p = 0.001, for each IQR increment) A positive association between mtDNA content and 8OHdG (' = 0.54 ± 0.05, p < 0.001) was shown. 8OHdG was estimated to mediate 42% of the positive association between PM10 exposure and mtDNA content during last trimester of pregnancy