Associations Between Perinatal Dioxin Exposure and Circadian Clock Gene mRNA Expression in Children in Dioxin-Contaminated Areas of Vietnam
Abstract
1. Introduction
2. Materials and Methods
2.1. Participants and Study Area
2.2. Dioxin Measurement
2.3. Quantification of Clock Genes Using Reverse Transcription Polymerase Chain Reaction
2.4. Sleep Duration and Behavioral Assessments
2.5. Statistical Analysis
3. Results
3.1. Characteristics of the Subjects and Sleep Duration
3.2. Relative BMAL1 Expression Levels and Perinatal Dioxin Exposure
3.3. Associations Between Relative BMAL1 Expression Levels and Neurodevelopmental Symptoms, as Indicated by Sleep Durations and ADHD-RS and C-CHARP Scores
3.4. Adjusted Associations Between Relative Expression Levels of Clock Genes Other than BMAL1 and Perinatal Dioxin Exposure Levels in Children with PER1 Detection
3.5. Adjusted Associations Between Relative Expression Levels of Clock Genes Other than BMAL1 and Neurodevelopmental Symptoms Indicated by Sleep Durations and ADHD and C-SHARP Scores in Children with PER1 Detection
4. Discussion
4.1. Impacts of Perinatal Dioxin Exposure on Clock Gene Expression Levels
4.2. Relationships Between Clock Gene Expression and Neurodevelopmental Symptoms, Sleep Durations, and ADHD-RS and C-SHARP Scores Examined at 8 Years of Age
4.3. Possible Mechanisms of Dioxin Exposure-Induced Alterations of Circadian Rhythms
4.4. Sex Different Effects of Perinatal Dioxin Exposure on Neurodevelopment
4.5. Strengths and Limitations
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Boys (N = 56) | Girls (N = 34) | |||||
---|---|---|---|---|---|---|
Units | Mean, [N] | SD, [%] | Mean, [N] | SD, [%] | ||
Birthweight | g | 3304.5 | 439.8 | 3113.2 | 386.0 | |
Gestational weeks | weeks | 39.6 | 0.8 | 39.5 | 0.8 | |
Maternal age at birth | years | 28.9 | 5.9 | 28.1 | 6.7 | |
Parity of mothers | % primiparae | [11] | [19.6] | [12] | [34.3] | |
Maternal education | years | 8.7 | 3.5 | 8.1 | 3.4 | |
Age at the survey | months | 105.0 | 1.7 | 105.7 | 1.7 | |
Weight at the survey | kg | 31.8 | 8.7 | 30.2 | 8.1 | |
Height at the survey | cm | 130.7 | 6.2 | 130.5 | 5.4 | |
BMI at the survey | kg/m2 | 18.4 | 3.7 | 17.5 | 3.8 | |
Weekdays | ||||||
Sleep duration at night | hours | 8.5 | 0.6 | 8.5 | 0.8 | |
Nap duration | minutes | 106.8 | 37.8 | 81.2 | 46.6 | * |
Total sleep duration | hours | 10.1 | 0.9 | 9.8 | 1.1 | |
Holydays | ||||||
Sleep duration at night | hours | 9.0 | 0.9 | 9.5 | 1.1 | * |
Nap duration | minutes | 84.8 | 64.3 | 78.5 | 59.1 | |
Total sleep duration | hours | 10.3 | 1.4 | 10.7 | 1.6 |
BMAL1 | Non-Detected | Detected | |||
---|---|---|---|---|---|
Mean | SD | Mean | SD | ||
Boys | N = 40 | N = 16 | |||
TCDD | 1.24 | 2.05 | 1.32 | 2.15 | |
TEQ−PCDDs | 7.20 | 1.60 | 7.13 | 1.56 | |
TEQ−PCDFs | 5.62 | 1.52 | 4.87 | 1.60 | |
TEQ−PCDD/Fs | 12.9 | 1.54 | 12.1 | 1.55 | |
Girls | N = 19 | N = 15 | |||
TCDD | 1.30 | 2.66 | 2.38 | 1.79 | * |
TEQ−PCDDs | 6.82 | 1.86 | 9.71 | 1.39 | |
TEQ−PCDFs | 5.04 | 1.78 | 8.05 | 1.38 | ** |
TEQ−PCDD/Fs | 12.0 | 1.78 | 17.9 | 1.36 | * |
BMAL1 | PER1 | CRY1 | CRY2 | |||
---|---|---|---|---|---|---|
Boys (N = 16) | ||||||
TCDD | −0.209 | 0.062 | −0.096 | −0.329 | ||
TEQ−PCDDs | −0.174 | 0.129 | −0.061 | −0.329 | ||
TEQ−PCDFs | −0.059 | 0.003 | −0.114 | −0.391 | ||
TEQ−PCDD/Fs | −0.185 | 0.059 | −0.121 | −0.403 | ||
Girls (N = 15) | ||||||
TCDD | 0.529 | * | −0.168 | 0.096 | -0.016 | |
TEQ−PCDDs | 0.418 | −0.221 | 0.168 | 0.082 | ||
TEQ−PCDFs | 0.393 | −0.564 | * | 0.168 | −0.115 | |
TEQ−PCDD/Fs | 0.525 | * | −0.339 | 0.236 | −0.016 |
Weekdays | Holydays | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Night Sleep | Nap | All Sleep | Night Sleep | Nap | All Sleep | |||||
Boys (N = 16) | ||||||||||
BMAL1 | 0.071 | −0.273 | −0.308 | −0.142 | 0.111 | −0.041 | ||||
PER1 | −0.086 | −0.271 | 0.083 | 0.267 | 0.230 | 0.311 | ||||
CRY1 | −0.322 | −0.080 | −0.020 | 0.071 | −0.260 | −0.222 | ||||
CRY2 | −0.204 | −0.356 | −0.219 | 0.241 | 0.053 | 0.119 | ||||
Girls (N = 15) | ||||||||||
BMAL1 | −0.532 | * | −0.483 | −0.640 | * | 0.585 | * | −0.006 | 0.368 | |
PER1 | −0.183 | 0.345 | 0.161 | −0.402 | −0.143 | −0.336 | ||||
CRY1 | −0.601 | * | 0.330 | −0.158 | 0.039 | 0.378 | 0.403 | |||
CRY2 | −0.218 | 0.696 | ** | 0.354 | −0.285 | 0.264 | 0.089 |
ADHD-RS | C-SHARP | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Inattention | Hyperactivity | ADHD | Verbal | Bulling | Covert | Hostility | Physical | ||||||
Boys (N = 16) | |||||||||||||
BMAL1 | 0.247 | 0.366 | 0.270 | 0.182 | 0.437 | 0.010 | 0.457 | 0.519 | * | ||||
PER1 | 0.534 | * | 0.373 | 0.392 | 0.364 | 0.127 | −0.004 | 0.474 | 0.385 | ||||
CRY1 | 0.413 | 0.146 | 0.199 | 0.470 | 0.353 | 0.394 | 0.491 | 0.561 | * | ||||
CRY2 | 0.563 | * | 0.465 | 0.503 | * | 0.355 | 0.314 | −0.016 | 0.756 | ** | 0.460 | ||
Girls (N = 15) | |||||||||||||
BMAL1 | 0.234 | 0.520 | * | 0.334 | 0.248 | 0.247 | 0.128 | 0.044 | 0.337 | ||||
PER1 | 0.343 | −0.624 | * | −0.489 | −0.175 | −0.383 | −0.265 | −0.039 | −0.452 | ||||
CRY1 | −0.322 | 0.054 | −0.138 | 0.118 | −0.136 | 0.141 | 0.000 | −0.115 | |||||
CRY2 | −0.577 | * | −0.247 | −0.411 | −0.312 | −0.384 | −0.222 | −0.228 | −0.390 |
PER1 | CRY1 | CRY2 | ||||||
---|---|---|---|---|---|---|---|---|
ρ | β | ρ | β | ρ | β | |||
Boys | (N = 56) | (N = 32) | (N = 41) | |||||
TCDD | 0.094 | 0.051 | −0.069 | 0.054 | −0.041 | 0.027 | ||
TEQ−PCDDs | 0.194 | 0.202 | −0.054 | −0.028 | 0.021 | 0.100 | ||
TEQ−PCDFs | 0.280 | * | 0.300 | * | 0.021 | 0.005 | 0.135 | 0.174 |
TEQ−PCDD/Fs | 0.241 | 0.255 | −0.033 | −0.017 | 0.069 | 0.137 | ||
Girls | (N = 34) | (N = 21) | (N = 31) | |||||
TCDD | −0.126 | −0.074 | −0.174 | −0.196 | −0.057 | −0.111 | ||
TEQ−PCDDs | −0.276 | −0.152 | −0.127 | −0.030 | −0.085 | −0.065 | ||
TEQ−PCDFs | −0.499 | ** | −0.394 | * | −0.153 | −0.038 | −0.266 | −0.206 |
TEQ−PCDD/Fs | −0.385 | * | −0.259 | −0.142 | −0.033 | −0.179 | −0.127 |
ADHD-RS | C-SHARP | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Inattention | Hyperactivity | ADHD | Verbal | Bulling | Covert | Hostility | Physical | ||||
Boys | ρ | 0.022 | −0.101 | −0.088 | 0.044 | −0.136 | −0.044 | 0.002 | 0.073 | ||
(N = 56) | β | 0.081 | −0.140 | −0.029 | −0.034 | −0.128 | −0.148 | 0.042 | 0.075 | ||
Girls | ρ | −0.051 | −0.301 | −0.165 | 0.507 | ** | 0.111 | 0.299 | 0.355 | * | 0.153 |
(N = 34) | β | −0.066 | −0.258 | −0.164 | 0.575 | ** | 0.303 | 0.336 | 0.423 | * | 0.160 |
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Pham, T.N.; Vu, H.T.; Tasaki, T.; Pham-The, T.; Tran, N.N.; Nishijo, M.; Tran, T.V.; Tran, H.A.; Takiguchi, T.; Nishino, Y. Associations Between Perinatal Dioxin Exposure and Circadian Clock Gene mRNA Expression in Children in Dioxin-Contaminated Areas of Vietnam. Toxics 2025, 13, 191. https://doi.org/10.3390/toxics13030191
Pham TN, Vu HT, Tasaki T, Pham-The T, Tran NN, Nishijo M, Tran TV, Tran HA, Takiguchi T, Nishino Y. Associations Between Perinatal Dioxin Exposure and Circadian Clock Gene mRNA Expression in Children in Dioxin-Contaminated Areas of Vietnam. Toxics. 2025; 13(3):191. https://doi.org/10.3390/toxics13030191
Chicago/Turabian StylePham, Thao Ngoc, Hoa Thi Vu, Takafumi Tasaki, Tai Pham-The, Nghi Ngoc Tran, Muneko Nishijo, Tien Viet Tran, Hai Anh Tran, Tomoya Takiguchi, and Yoshikazu Nishino. 2025. "Associations Between Perinatal Dioxin Exposure and Circadian Clock Gene mRNA Expression in Children in Dioxin-Contaminated Areas of Vietnam" Toxics 13, no. 3: 191. https://doi.org/10.3390/toxics13030191
APA StylePham, T. N., Vu, H. T., Tasaki, T., Pham-The, T., Tran, N. N., Nishijo, M., Tran, T. V., Tran, H. A., Takiguchi, T., & Nishino, Y. (2025). Associations Between Perinatal Dioxin Exposure and Circadian Clock Gene mRNA Expression in Children in Dioxin-Contaminated Areas of Vietnam. Toxics, 13(3), 191. https://doi.org/10.3390/toxics13030191