ABSTRACT
Previous studies suggest a negative association between prenatal polybrominated diphenyl ethers (PBDEs) exposure and child cognitive and psychomotor development. However, the timing of the relationship between PBDE exposure and neurodevelopment is still unclear. We examined the association between PBDE concentration at two different prenatal times (early and late pregnancy) and cognitive function in children 6-8 years of age. METHODS: Eight hundred pregnant women were recruited between 2007 and 2009 from Sherbrooke, Canada. Four PBDE congeners (BDE-47, -99, -100, and -153) were measured in maternal plasma samples collected during early pregnancy (12 weeks of gestation) and at delivery. At 6-8 years of age, 355 children completed a series of subtests spanning multiple neuropsychologic domains: verbal and memory skills were measured using the Wechsler Intelligence Scale for Children, Fourth Edition; visuospatial processing using both Wechsler Intelligence Scale for Children, Fourth Edition and Neuropsychological Assessment second edition; and attention was assessed through the Test of Everyday Attention for Children. Additionally, parents completed subtests from the Developmental Coordination Disorder Questionnaire to measure child motor control. We used linear regression and quantile g-computation models to estimate associations of PBDE congener concentrations and psychologic test scores. RESULTS: In our models, no significant associations were detected between PBDE mixture and any of the child psychologic scores. BDE-99 concentration at delivery was nominally associated with higher scores on short-term and working memory while a decrease in spatial perception and reasoning was nominally associated with higher BDE-100 concentration at delivery. CONCLUSION: Overall, our results did not show a significant association between PBDEs and child cognitive and motor development.
ABSTRACT
BACKGROUND: Post-transcriptional modifications of RNA constitute fundamental mechanisms of gene regulation. N6-methyladenosine (m6A) is critical for health and disease and is modulated by cellular stressors. However, associations between environmental exposures and m6A have not been studied in humans. We aimed to examine associations between tobacco smoking and particulate air pollution with m6A and mRNA expression levels of its reader, writer and eraser (RWE) genes in blood. METHODS: Using the Beijing Truck Driver Air Pollution Study, we investigated global m6A in RNA from peripheral blood collected from 106 human subjects in Beijing, China, in 2008. We measured m6A with nano-flow liquid chromatography-tandem mass spectrometry and investigated gene expression of six m6A RWEs with real-time-quantitative PCR. Using linear models, we examined associations with smoking status, pack-years, and smoking on day of visit in men, and with environmental tobacco smoke in nonsmokers. We also examined associations with ambient PM10 (particulate matter ≤ 10 µm in diameter), and personal black carbon (BC) and PM2.5 measured with a portable monitor. RESULTS: Smoking in men was significantly associated with a relative 10.7% decrease in global m6A levels in comparison to nonsmokers (p = 0.02). In men, smoking greater than 3.8 pack-years was associated with a 14.9% lower m6A than in nonsmokers. BC exposure trended towards positive associations with m6A (5.95% per 10 µg/m3 increase in BC; 95% CI: -0.96, 13.3). Global m6A levels were not correlated with RWE gene expression levels. No associations were detected between smoking or air pollutants and m6A RWE gene expression. DISCUSSION: m6A was negatively associated with long-term smoking, yet positively associated with short-term BC exposure. These results indicate variable m6A responses to environmental stressors, providing early evidence into the impacts of toxicants on RNA modifications and suggesting potential for m6A as a biomarker or mechanism in environmental health research.
