{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:00:47Z","timestamp":1760058047616,"version":"build-2065373602"},"reference-count":35,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T00:00:00Z","timestamp":1741305600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education, Sports, Science and Culture, Japan","award":["17H04665"],"award-info":[{"award-number":["17H04665"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/toxics13030191","type":"journal-article","created":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T04:29:59Z","timestamp":1741321799000},"page":"191","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Associations Between Perinatal Dioxin Exposure and Circadian Clock Gene mRNA Expression in Children in Dioxin-Contaminated Areas of Vietnam"],"prefix":"10.3390","volume":"13","author":[{"given":"Thao Ngoc","family":"Pham","sequence":"first","affiliation":[{"name":"Department of Functional Diagnosis, Military Hospital 103, Vietnam Military Medical University, Hanoi 12108, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hoa Thi","family":"Vu","sequence":"additional","affiliation":[{"name":"Department of Military Hygiene, Vietnam Military Medical University, Hanoi 12108, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9291-1415","authenticated-orcid":false,"given":"Takafumi","family":"Tasaki","sequence":"additional","affiliation":[{"name":"Department of Life Science, Medical Research Institute, Kanazawa Medical University, Ishikawa 920-0293, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5878-7307","authenticated-orcid":false,"given":"Tai","family":"Pham-The","sequence":"additional","affiliation":[{"name":"Biomedical and Pharmaceutical Research Centre, Vietnam Military Medical University, Hanoi 12108, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nghi Ngoc","family":"Tran","sequence":"additional","affiliation":[{"name":"Ministry of Health, Vietnamese Government, Hanoi 10060, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muneko","family":"Nishijo","sequence":"additional","affiliation":[{"name":"Epidemiology and Public Health, Kanazawa Medical University, Ishikawa 920-0293, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tien Viet","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Infectious and Tropical Diseases, Military Hospital 103, Vietnam Military Medical University, Hanoi 12108, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hai Anh","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Physiology, Vietnam Military Medical University, Hanoi 12108, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7979-3813","authenticated-orcid":false,"given":"Tomoya","family":"Takiguchi","sequence":"additional","affiliation":[{"name":"Epidemiology and Public Health, Kanazawa Medical University, Ishikawa 920-0293, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshikazu","family":"Nishino","sequence":"additional","affiliation":[{"name":"Epidemiology and Public Health, Kanazawa Medical University, Ishikawa 920-0293, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,7]]},"reference":[{"key":"ref_1","unstructured":"Reddy, S., Reddy, V., and Sharma, S. (2023). Physiology, Circadian Rhythm. StatPearls, StatPearls Publishing."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/s41580-019-0179-2","article-title":"Molecular mechanisms and physiological importance of circadian rhythms","volume":"21","author":"Patke","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_3","first-page":"23","article-title":"2,3,7,8-Tetrachlorodibenzo-p-dioxin phase advances the deer mouse (Peromyscus maniculatur) circadian rhythm by altering expression of clock proteins","volume":"42","author":"Miller","year":"1999","journal-title":"Organohal. Comp."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Fader, K.A., Nault, R., Doskey, C.M., Fling, R.R., and Zacharewski, T.R. (2019). 2,3,7,8-Tetrachlorodibenzo-p-dioxin abolishes circadian regulation of hepatic metabolic activity in mice. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-42760-3"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1177\/0748730408316022","article-title":"Behavioral rhythmicity of mice lacking AhR and attenuation of light-induced phase shift by 2,3,7,8-tetrachlorodibenzo-p-dioxin","volume":"23","author":"Mukai","year":"2008","journal-title":"J. Biol. Rhythms"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Pham-The, T., Nishijo, M., Pham, T.N., Vu, H.T., Tran, N.N., Tran, A.H., Hoang, L.V., Do, Q., Nishino, Y., and Nishijo, H. (2022). Perinatal Dioxin Exposure and Attention Deficit Hyperactivity Disorder (ADHD) Symptoms in Children Living in a Dioxin Contamination Hotspot in Vietnam. Toxics, 10.","DOI":"10.3390\/toxics10050212"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.pnpbp.2016.01.006","article-title":"Circadian rhythms and attention deficit hyperactivity disorder: The what, the when and the why","volume":"67","author":"Coogan","year":"2016","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3858","DOI":"10.1111\/ejn.16423","article-title":"The circadian system: A neglected player in neurodevelopmental disorders","volume":"60","author":"Bouteldja","year":"2024","journal-title":"Eur. J. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.neubiorev.2016.11.002","article-title":"Clock genes, ADHD and aggression","volume":"91","author":"Mogavero","year":"2018","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1016\/S0002-9440(10)64135-1","article-title":"Circadian expression of clock genes in human oral mucosa and skin: Association with specific cell-cycle phases","volume":"158","author":"Bjarnason","year":"2001","journal-title":"Am. J. Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6625","DOI":"10.1021\/es201666d","article-title":"Dioxin concentrations in breast milk of Vietnamese nursing mothers: A survey four decades after the herbicide spraying","volume":"45","author":"Tai","year":"2011","journal-title":"Environ. Sci. Technol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Tran, N.N., Pham-The, T., Pham, T.N., Vu, H.T., Luong, K.N., and Nishijo, M. (2023). Neurodevelopmental Effects of Perinatal TCDD Exposure Differ from Those of Other PCDD\/Fs in Vietnamese Children Living near the Former US Air Base in Da Nang, Vietnam. Toxics, 11.","DOI":"10.3390\/toxics11020103"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"141083","DOI":"10.1016\/j.scitotenv.2020.141083","article-title":"Dioxin exposure and sexual dimorphism of gaze behavior in prepubertal Vietnamese children living in Da Nang, a hot spot for dioxin contamination","volume":"749","author":"Pham","year":"2020","journal-title":"Sci. Total Environ."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1093\/toxsci\/kfl055","article-title":"The 2005 World Health Organization reevaluation of human and Mammalian toxic equivalency factors for dioxins and dioxin-like compounds","volume":"93","author":"Birnbaum","year":"2006","journal-title":"Toxicol. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"DuPaul, G.J., Power, T.J., Anastopoulos, A.D., and Reid, R. (1998). ADHD Rating Scale\u2014IV: Checklists, Norms, and Clinical Interpretation, Guilford Press.","DOI":"10.1037\/t00680-000"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1016\/j.ridd.2009.03.001","article-title":"Development of the Children\u2019s Scale of Hostility and Aggression: Reactive\/Proactive (C-SHARP)","volume":"30","author":"Farmer","year":"2009","journal-title":"Res. Dev. Disabil."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1124\/mol.105.021006","article-title":"The aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin alters the circadian rhythms, quiescence, and expression of clock genes in murine hematopoietic stem and progenitor cells","volume":"69","author":"Garrett","year":"2006","journal-title":"Mol. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1124\/mol.107.039305","article-title":"Disruption of clock gene expression alters responses of the aryl hydrocarbon receptor signaling pathway in the mouse mammary gland","volume":"72","author":"Qu","year":"2007","journal-title":"Mol. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1038\/s41386-019-0327-6","article-title":"Impact of adult attention deficit hyperactivity disorder and medication status on sleep\/wake behavior and molecular circadian rhythms","volume":"44","author":"Coogan","year":"2019","journal-title":"Neuropsychopharmacology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1038\/mp.2011.149","article-title":"Adult attention-deficit hyperactivity disorder is associated with alterations in circadian rhythms at the behavioural, endocrine and molecular levels","volume":"17","author":"Baird","year":"2012","journal-title":"Mol. Psychiatry"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Duck, A., Reis, O., Wagner, H., Wunsch, K., Hassler, F., Kolch, M., Astiz, M., Thome, J., Berger, C., and Oster, H. (2022). Clock Genes Profiles as Diagnostic Tool in (Childhood) ADHD-A Pilot Study. Brain Sci., 12.","DOI":"10.3390\/brainsci12091198"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1615\/CritRevEukarGeneExpr.v18.i3.20","article-title":"The aryl hydrocarbon receptor complex and the control of gene expression","volume":"18","author":"Beischlag","year":"2008","journal-title":"Crit. Rev. Eukaryot. Gene Expr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1146\/annurev-physiol-021909-135922","article-title":"Mammalian Per-Arnt-Sim proteins in environmental adaptation","volume":"72","author":"McIntosh","year":"2010","journal-title":"Annu. Rev. Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.toxlet.2010.03.020","article-title":"The clock genes period 1 and period 2 mediate diurnal rhythms in dioxin-induced Cyp1A1 expression in the mouse mammary gland and liver","volume":"196","author":"Qu","year":"2010","journal-title":"Toxicol. Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"11700","DOI":"10.3390\/ijms150711700","article-title":"Interplay between Dioxin-mediated signaling and circadian clock: A possible determinant in metabolic homeostasis","volume":"15","author":"Wang","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/S0165-0173(03)00171-1","article-title":"A molecular perspective of human circadian rhythm disorders","volume":"42","author":"Cermakian","year":"2003","journal-title":"Brain Res. Brain Res. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/0041-008X(87)90295-X","article-title":"Circadian alterations in prolactin, corticosterone, and thyroid hormone levels and down-regulation of prolactin receptor activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin","volume":"87","author":"Jones","year":"1987","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.aquatox.2012.12.009","article-title":"Toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the peripheral nervous system of developing red seabream (Pagrus major)","volume":"128\u2013129","author":"Iida","year":"2013","journal-title":"Aquat. Toxicol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.ntt.2015.10.005","article-title":"Developmental origin of abnormal dendritic growth in the mouse brain induced by in utero disruption of aryl hydrocarbon receptor signaling","volume":"52","author":"Kimura","year":"2015","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.brainresrev.2009.11.002","article-title":"Role of glial cells in the formation and maintenance of synapses","volume":"63","author":"Pfrieger","year":"2010","journal-title":"Brain Res. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/j.ceb.2010.07.005","article-title":"Assisted morphogenesis: Glial control of dendrite shapes","volume":"22","author":"Procko","year":"2010","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"131499","DOI":"10.1016\/j.jhazmat.2023.131499","article-title":"Exposure to polychlorinated biphenyls selectively dysregulates endothelial circadian clock and endothelial toxicity","volume":"454","author":"Teglas","year":"2023","journal-title":"J. Hazard. Mater."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"108001","DOI":"10.1016\/j.neuropsychologia.2021.108001","article-title":"Effects of perinatal dioxin exposure on mirror neuron activity in 9-year-old children living in a hot spot of dioxin contamination in Vietnam","volume":"161","author":"Vu","year":"2021","journal-title":"Neuropsychologia"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/s41390-018-0187-5","article-title":"Sex-specific alterations in preterm brain","volume":"85","author":"Benavides","year":"2019","journal-title":"Pediatr. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1080\/17588928.2020.1800617","article-title":"Development of sex differences in the human brain","volume":"12","author":"Kurth","year":"2021","journal-title":"Cogn. Neurosci."}],"container-title":["Toxics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2305-6304\/13\/3\/191\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:48:45Z","timestamp":1760028525000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2305-6304\/13\/3\/191"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,7]]},"references-count":35,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["toxics13030191"],"URL":"https:\/\/doi.org\/10.3390\/toxics13030191","relation":{},"ISSN":["2305-6304"],"issn-type":[{"type":"electronic","value":"2305-6304"}],"subject":[],"published":{"date-parts":[[2025,3,7]]}}}