Associations Between Perinatal Dioxin Exposure and Circadian Clock Gene mRNA Expression in Children in Dioxin-Contaminated Areas of Vietnam

We investigated the impact of perinatal dioxin exposure (indicated by dioxin levels in maternal breast milk) on clock gene mRNA expression in buccal cells of 9-year-old children from the Da Nang birth cohort in Vietnam using reverse transcription polymerase chain reaction. Of the 56 boys and 34 girls (67% detection rate) in whom <i>PER1</i> was detected, <i>BMAL1</i> was detected in only 16 boys and 15 girls. Dioxin levels were significantly higher in girls with <i>BMAL1</i> detection than in girls without detection. In girls, higher relative <i>BMAL1</i> expression levels were associated with greater levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin and toxic equivalents of polychlorinated dibenzodioxins and polychlorinated dibenzofurans. Moreover, <i>BMAL1</i> expression levels were correlated with shorter night sleep duration on weekdays, greater sleep duration on holidays, and higher hyperactivity scores. After adjusting for maternal parity, relative <i>PER1</i> expression levels were higher in boys with higher toxic equivalents of polychlorinated dibenzofuran than those in girls. Although higher <i>PER1</i> expression levels were correlated with greater verbal aggression and hostility scores in girls, no such associations were found in boys. These findings suggest the possible existence of sex-specific effects of perinatal dioxin exposure on circadian rhythms regulated by clock genes, particularly <i>BMAL1</i>, leading to sleep and behavioral problems in later life.