Autism spectrum disorder-like behavior induced in rat offspring by perinatal exposure to di-(2-ethylhexyl) phthalate

Li, Yao; Zhao, Yun; Lu, Yu; Lu, Xianxian; Hu, Yingdan; Li, Qiulin; Shuai, Menglei; Li, Rui

doi:10.1007/s11356-022-19531-1

Cited by 9 publications

(5 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, one study found that di(2-ethylhexyl) phthalate (DEHP) exposure during pregnancy induced ASDrelated behavioral abnormalities in rat offspring. 17 Results from human studies of the association between urinary phthalate metabolite concentrations during pregnancy and ASD-related outcomes are inconclusive. 18,19 One casecontrol study showed that metabolites of DEHP, including mono-2-ethylhexyl phthalate (MEHP), were elevated in children with ASD compared with controls.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A Mixture of Urinary Phthalate Metabolite Concentrations During Pregnancy and Offspring Social Responsiveness Scale Scores

Yu,

Braun,

Lyall

et al. 2023

Epidemiology

View full text Add to dashboard Cite

Background: Phthalates are a group of chemicals with ubiquitous exposure worldwide. Exposures to phthalates during pregnancy may play a role in autism spectrum disorder (ASD) etiology by disrupting hormone levels or directly impacting fetal neurodevelopment. However, there is little research quantifying the aggregate effect of phthalates on child ASD-related behaviors. Methods: We used data from two prospective pregnancy and birth cohorts – the Health Outcomes and Measures of the Environment (HOME) and the Early Autism Risk Longitudinal Investigation (EARLI). HOME is a general population cohort while participants in EARLI were at higher familial risk for ASD. Using quantile g-computation and linear regression models, we assessed the joint and individual associations of a mixture of six phthalate metabolites during pregnancy with child ASD-related traits measured by Social Responsiveness Scale (SRS) scores at ages 3-8 years. Results: Our analyses included 271 participants from HOME and 166 from EARLI. There were imprecise associations between the phthalate mixture and SRS total raw scores in HOME (difference in SRS scores per decile increase in every phthalate = 1.3; 95% confidence interval [CI]: -0.2, 2.8) and EARLI (difference in SRS scores per decile increase in every phthalate = -0.9; 95% CI: -3.5, 1.7). Conclusions: The cohort-specific effect sizes of the pthalates–SRS associations were small and confidence intervals were imprecise. These results suggest that if there are associations between phthalate metabolites during pregnancy and child SRS scores, they may differ across populations with different familial liabilities. Further studies with larger sample sizes are warranted.

show abstract

Section: Discussionmentioning

confidence: 99%

“…For example, one study found that di(2-ethylhexyl) phthalate (DEHP) exposure during pregnancy induced ASD-related behavioral abnormalities in rat offspring. 17…”

mentioning

confidence: 99%

A Mixture of Urinary Phthalate Metabolite Concentrations During Pregnancy and Offspring Social Responsiveness Scale Scores

Yu,

Braun,

Lyall

et al. 2023

Epidemiology

View full text Add to dashboard Cite

show abstract

“…The valproic acid (VPA)-exposed rat offspring have been shown to spend significantly more time self-grooming than control rats, suggesting ASD-related stereotyped behavior [ 73 , 85 ]. Furthermore, di-(2-ethylhexyl) phthalate (DEHP) exposure has been shown to result in autism-like behavior, illustrated in part by the increased self-grooming time, which is comparable to the elevated duration observed in VPA rats [ 86 ]. Our results are in agreement with these studies as we observed that the Ko rats self-groomed significantly more frequently and for longer durations than the WT animals, thus exhibiting ASD-like phenotype.…”

Section: Discussionmentioning

confidence: 99%

Genetic ablation of metabotropic glutamate receptor 5 in rats results in an autism-like behavioral phenotype

et al. 2022

View full text Add to dashboard Cite

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in communication, and social skills, as well as repetitive and/or restrictive interests and behaviors. The severity of ASD varies from mild to severe, drastically interfering with the quality of life of affected individuals. The current occurrence of ASD in the United States is about 1 in 44 children. The precise pathophysiology of ASD is still unknown, but it is believed that ASD is heterogeneous and can arise due to genetic etiology. Although various genes have been implicated in predisposition to ASD, metabotropic glutamate receptor 5 (mGluR5) is one of the most common downstream targets, which may be involved in autism. mGluR5 signaling has been shown to play a crucial role in neurodevelopment and neural transmission making it a very attractive target for understanding the pathogenesis of ASD. In the present study, we determined the effect of genetic ablation of mGluR5 (Grm5) on an ASD-like phenotype using a rat model to better understand the role of mGluR5 signaling in behavior patterns and clinical manifestations of ASD. We observed that mGluR5 Ko rats exhibited exaggerated self-grooming and increased marble burying, as well as deficits in social novelty. Our results suggest that mGluR5 Ko rats demonstrate an ASD-like phenotype, specifically impaired social interaction as well as repetitive and anxiety-like behavior, which are correlates of behavior symptoms observed in individuals with ASD. The mGluR5 Ko rat model characterized in this study may be explored to understand the molecular mechanisms underlying ASD and for developing effective therapeutic modalities.

show abstract

“…To understand how phthalates can be responsible for the development of ASD, Li and colleagues, using an animal model, observed an increase in the expression of components related to the mTOR pathway and the inhibition of autophagy in the brains of offspring exposed to phthalates during the perinatal period [ 60 ]. These alterations may be responsible for the development of symptoms resembling the autistic spectrum in these animals [ 60 ].…”

Section: The Influence Of Environmental Hazardsmentioning

confidence: 99%

The Autism Spectrum Disorder and Its Possible Origins in Pregnancy

Botelho,

Silva,

Borbely

2024

IJERPH

View full text Add to dashboard Cite

Autism Spectrum Disorder (ASD) belongs to the group of neurodevelopmental disorders, and has a high prevalence, affecting 1 in 100 children according to data from the World Health Organization (WHO). To be diagnosed with ASD, the child must have persistent deficits in communication and social interactions, and restricted and repetitive patterns of behavior, interests, or activities. Despite its prevalence, the etiology of ASD is still uncertain, with multifactorial characteristics, including those associated with the gestational period, where maternal exposure to biological, chemical, or physical hazards occurs, some of which have already been proposed as causes of ASD outcomes. Since pregnancy requires a balance between the maternal–fetal binomial, the breakdown of this balance caused by such environmental hazards can lead to altered fetal neurodevelopment, including ASD. With this firmly in mind, this review aims to compile the most recent data on the gestational causes that may be associated with the development of ASD to help health professionals identify risk factors and act for the prevention and management of ASD.

show abstract

Autism spectrum disorder-like behavior induced in rat offspring by perinatal exposure to di-(2-ethylhexyl) phthalate

Cited by 9 publications

References 62 publications

A Mixture of Urinary Phthalate Metabolite Concentrations During Pregnancy and Offspring Social Responsiveness Scale Scores

A Mixture of Urinary Phthalate Metabolite Concentrations During Pregnancy and Offspring Social Responsiveness Scale Scores

Genetic ablation of metabotropic glutamate receptor 5 in rats results in an autism-like behavioral phenotype

The Autism Spectrum Disorder and Its Possible Origins in Pregnancy

Contact Info

Product

Resources

About