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Published on: November 11, 2016
Associations Between Perinatal Dioxin Exposure and Circadian Clock Gene mRNA Expression in Children in
Thao Ngoc Pham1, Hoa Thi Vu2, Takafumi Tasaki3
1Department of Functional Diagnosis, Military Hospital 103, Vietnam Military Medical University, Hanoi 12108, Vietnam.
Insights
Perinatal dioxin exposure impacts clock genes like BMAL1 in children, potentially causing sleep and behavioral issues. These effects appear sex-specific, with girls showing stronger associations between dioxin levels and gene expression.
Area of Science:
- Environmental Health
- Molecular Biology
- Chronobiology
Background:
- Perinatal exposure to environmental toxins, such as dioxins, can have long-term health consequences.
- Circadian rhythms, regulated by clock genes, are crucial for maintaining physiological and behavioral homeostasis.
- Disruptions in circadian rhythms have been linked to various health problems, including sleep and behavioral disorders.
Purpose of the Study:
- To investigate the association between perinatal dioxin exposure and clock gene mRNA expression (PER1 and BMAL1) in children.
- To explore potential sex-specific effects of dioxin exposure on circadian gene expression and related outcomes.
- To examine the relationship between clock gene expression, sleep patterns, and behavioral scores in children exposed to dioxins.
Main Methods:
- Analysis of dioxin levels in maternal breast milk as an indicator of perinatal exposure.
- Measurement of PER1 and BMAL1 mRNA expression in buccal cells of 9-year-old children using reverse transcription polymerase chain reaction.
- Statistical analysis to assess correlations between dioxin levels, gene expression, sleep duration, and behavioral scores, with adjustments for potential confounders.
Main Results:
- Dioxin levels were significantly higher in girls with detectable BMAL1 expression compared to those without.
- Higher BMAL1 expression in girls correlated with increased levels of dioxins and toxic equivalents, shorter weekday sleep, longer holiday sleep, and higher hyperactivity.
- PER1 expression showed sex-specific associations, with higher levels linked to dioxins in boys and verbal aggression/hostility in girls.
Conclusions:
- Perinatal dioxin exposure may exert sex-specific effects on the expression of clock genes, particularly BMAL1.
- Altered clock gene expression due to dioxin exposure could contribute to sleep disturbances and behavioral problems in children.
- These findings highlight the importance of considering sex as a factor in environmental health research related to circadian rhythm disruption.
Abstract:
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 PER1 was detected, BMAL1 was detected in only 16 boys and 15 girls. Dioxin levels were significantly higher in girls with BMAL1 detection than in girls without detection. In girls, higher relative BMAL1 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, BMAL1 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 PER1 expression levels were higher in boys with higher toxic equivalents of polychlorinated dibenzofuran than those in girls. Although higher PER1 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 BMAL1, leading to sleep and behavioral problems in later life.
