Gestational and lactational exposure to 2,3,7,8-tetrachlorodibenzo--dioxin affects social behaviors between developing rhesus monkeys ()

Negishi, Takayuki; Shimomura, Hiromi; Koyama, Tomotsugu; Kawasaki, Katsuyoshi; Ishii, Yoshiyuki; Kyuwa, Shigeru; Yasuda, Mineo; Kuroda, Yoichiro; Yoshikawa, Yasuhiro

doi:10.1016/j.toxlet.2005.07.008

Cited by 22 publications

(25 citation statements)

References 23 publications

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“…However, in a recent study, Braun et al [28] found PCB-178 to be associated with less autistic behaviour. Additionally, Negishi and coworkers [31] investigated rhesus monkeys, prenatally exposed to TCDD, a prototype for PCDD/F, and found TCDD-exposed monkeys to show more visual exploration and more mutual proximity in a social interaction with a peer subject and less stereotypic behaviour than control monkeys. Deficits in social interaction and stereotypic behaviour alongside impaired communication form the triad upon which autism is diagnosed.…”

Section: Discussionmentioning

confidence: 99%

“…However, this was only true for TCDD levels but not for total PCDD/F concentrations. Increased PCB levels were also related to less social behaviour in infant cynomolgus monkeys [30] whereas increased levels of TCDD were related to more exploration and proximity in social interaction in rhesus monkeys [31]. For a review on environmental contributions to the aetiology of autism, see [32].…”

Section: Introductionmentioning

confidence: 99%

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Influence of Low-Level Prenatal Exposure to PCDD/Fs and PCBs on Empathizing, Systemizing and Autistic Traits: Results from the Duisburg Birth Cohort Study

et al. 2015

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BackgroundPolychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) are assumed to act as endocrine disruptor chemicals. Prenatal exposure to these pollutants might influence fetal steroid hormone levels, which are thought to be related to sex-typical development and autistic traits.ObjectivesWe examined associations of prenatal levels of PCDD/Fs and PCBs with autism traits and sex-typical behaviour in childhood.MethodsWe measured levels of PCDD/Fs and PCBs in maternal blood samples during pregnancy using gas chromatography/high-resolution mass spectrometry. Sex-typical behaviour was assessed at 9 years of age (n = 96) and autistic traits at 10 years of age using the Social Responsiveness Scale (SRS; n = 100). Multiple regression analyses were conducted to estimate the associations between prenatal exposure and outcome variables.ResultsBlood concentrations (WHO2005-TEq) of ƩPCDD/Fs ranged from 2.93–46.45 pg/g lipid base (median = 12.91 pg/g lipid base) and concentrations of ƩPCBs were in the range of 1.24–25.47 pg/g lipid base (median = 6.85 pg/g lipid base) which is within the range of German background exposure. We found significant negative associations between PCDD/F levels in maternal blood and SRS scores in the whole group (β = -6.66, p < .05), in girls (β = -10.98, p < .05) and, in one SRS subscale, in boys (β = -6.86, p < .05). For PCB levels, associations with one SRS subscale were significant for the whole study group as were associations with two subscales in girls. We did not find significant associations between PCDD/F or PCB levels and sex-typical behaviour for either sex.ConclusionsIn an earlier part of this study, prenatal exposure to PCDD/Fs and PCBs was found to be associated with lower testosterone levels, therefore, our findings are consistent with the idea that autism spectrum conditions are related to fetal androgen levels. Several possible mechanisms, through which PCDD/Fs and PCBs might influence autistic behaviour, are discussed.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Influence of Low-Level Prenatal Exposure to PCDD/Fs and PCBs on Empathizing, Systemizing and Autistic Traits: Results from the Duisburg Birth Cohort Study

et al. 2015

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“…Mice gestationally exposed to TCDD not only have developmental and embryotoxic effects, but also have a teratogenic response characterized by the induction of cleft palate, hydronephrosis and thymic atrophy (Couture et al, 1990a). Higher mammalian species, such as monkeys, are also sensitive to gestational TCDD exposure and exhibit developmental, embryotoxic and teratogenic responses (Giavini et al, 1983;McNulty, 1984;Negishi et al, 2006;Yasuda et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Comparative developmental toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the hamster, rat and guinea pig

2007

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“…While the precise anatomical regions and cell types targeted by TCDD are largely unidentified, the functional abnormalities may be consistent with findings of improper brain maturation in epidemiological and experimental animal studies. Experimental animal studies have indicated that perinatal exposure to TCDD has a marked effect on learning ability in rats and monkeys [7-9]. Epidemiological studies have suggested that children accidentally exposed to PCB and dioxins exhibit delayed motor development and show a tendency to hyperactivity [10].…”

Section: Introductionmentioning

confidence: 99%

Effect of dioxins on regulation of tyrosine hydroxylase gene expression by aryl hydrocarbon receptor: a neurotoxicology study

et al. 2009

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BackgroundDioxins and related compounds are suspected of causing neurological disruption. Epidemiological studies indicated that exposure to these compounds caused neurodevelopmental disturbances such as learning disability and attention deficit hyperactivity disorder, which are thought to be closely related to dopaminergic dysfunction. Although the molecular mechanism of their actions has not been fully investigated, a major participant in the process is aryl hydrocarbon receptor (AhR). This study focused on the effect of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) exposure on the regulation of TH, a rate-limiting enzyme of dopamine synthesis, gene expression by AhR.MethodsN2a-Rβ cells were established by transfecting murine neuroblastoma Neuro2a with the rat AhR cDNA. TH expression induced by TCDD was assessed by RT-PCR and Western blotting. Participation of AhR in TCDD-induced TH gene expression was confirmed by suppressing AhR expression using the siRNA method. Catecholamines including dopamine were measured by high-performance liquid chromatography. A reporter gene assay was used to identify regulatory motifs in the promoter region of TH gene. Binding of AhR with the regulatory motif was confirmed by an electrophoretic mobility shift assay (EMSA).ResultsInduction of TH by TCDD through AhR activation was detected at mRNA and protein levels. Induced TH protein was functional and its expression increased dopamine synthesis. The reporter gene assay and EMSA indicated that AhR directly regulated TH gene expression. Regulatory sequence called aryl hydrocarbon receptor responsive element III (AHRE-III) was identified upstream of the TH gene from -285 bp to -167 bp. Under TCDD exposure, an AhR complex was bound to AHRE-III as well as the xenobiotic response element (XRE), though AHRE-III was not identical to XRE, the conventional AhR-binding motif.ConclusionOur results suggest TCDD directly regulate the dopamine system by TH gene transactivation via an AhR-AHRE-III-mediated pathway. The AhR- mediated pathway could have a particular AhR-mediated genomic control pathway transmitting the effects of TCDD action to target cells in the development of dopaminergic disabilities.

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Gestational and lactational exposure to 2,3,7,8-tetrachlorodibenzo--dioxin affects social behaviors between developing rhesus monkeys ()

Cited by 22 publications

References 23 publications

Influence of Low-Level Prenatal Exposure to PCDD/Fs and PCBs on Empathizing, Systemizing and Autistic Traits: Results from the Duisburg Birth Cohort Study

Influence of Low-Level Prenatal Exposure to PCDD/Fs and PCBs on Empathizing, Systemizing and Autistic Traits: Results from the Duisburg Birth Cohort Study

Comparative developmental toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the hamster, rat and guinea pig

Effect of dioxins on regulation of tyrosine hydroxylase gene expression by aryl hydrocarbon receptor: a neurotoxicology study

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