Ubiquitous plasticizer, Di-(2-ethylhexyl) phthalate enhances existing inflammatory profile in monocytes of children with autism

Nadeem, Ahmed; Ahmad, Sheikh F.; Al-Harbi, Naif O.; Al-Ayadhi, Laila; Attia, Sabry M.; Alasmari, Abdullah F.; Sobeai, Homood M. As; Bakheet, Saleh A.

doi:10.1016/j.tox.2020.152597

Cited by 26 publications

(9 citation statements)

References 53 publications

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“…Analyses using IPA suggested that prenatal exposure to MCPP in males and ΣDINCH in females were all linked with enrichment in pathways related to PPARα, mirroring results from other human epigenetic studies using targeted approaches (in association with MCPP, BBzP, DEHP) ( Montrose et al, 2018 ). Other research has proposed that phthalates and their metabolites may act through inflammatory pathways (e.g., NF-κB, TNF-β) ( Ferguson et al, 2011 ; Ferguson et al, 2014 ; Kelley et al, 2019 ; Nadeem et al, 2020 ), hormone disruption (e.g., antiandrogenic processes) ( Kay et al, 2013 ; Kay et al, 2014 ; Axelsson et al, 2015 ; Montrose et al, 2018 ), and altered lipid metabolism (e.g., mitochondrial dysfunction) ( LaRocca et al, 2014 ; Benjamin et al, 2017 ; Braun, 2017 ; Montrose et al, 2018 ). Enriched pathways presently echoed these proposed mechanisms, with altered DNA methylation in pathways related to TNF-β signaling (BBzP in females), androgen signaling (ΣDEHP in females), and mitochondrial functions (ΣDEHP in males; DnBP in females).…”

Section: Discussionmentioning

confidence: 99%

Prenatal Exposures to Common Phthalates and Prevalent Phthalate Alternatives and Infant DNA Methylation at Birth

et al. 2022

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Phthalates are a diverse group of chemicals used in consumer products. Because they are so widespread, exposure to these compounds is nearly unavoidable. Recently, growing scientific consensus has suggested that phthalates produce health effects in developing infants and children. These effects may be mediated through mechanisms related to the epigenome, the constellation of mitotically heritable chemical marks and small compounds that guide transcription and translation. The present study examined the relationship between prenatal, first-trimester exposure of seven phthalates and epigenetics in two pregnancy cohorts (n = 262) to investigate sex-specific alterations in infant blood DNA methylation at birth (cord blood or neonatal blood spots). Prenatal exposure to several phthalates was suggestive of association with altered DNA methylation at 4 loci in males (all related to ΣDEHP) and 4 loci in females (1 related to ΣDiNP; 2 related to BBzP; and 1 related to MCPP) at a cutoff of q < 0.2. Additionally, a subset of dyads (n = 79) was used to interrogate the relationships between two compounds increasingly used as substitutions for common phthalates (ΣDINCH and ΣDEHTP) and cord blood DNA methylation. ΣDINCH, but not ΣDEHTP, was suggestive of association with DNA methylation (q < 0.2). Together, these results demonstrate that prenatal exposure to both classically used phthalate metabolites and their newer alternatives is associated with sex-specific infant DNA methylation. Research and regulatory actions regarding this chemical class should consider the developmental health effects of these compounds and aim to avoid regrettable substitution scenarios in the present and future.

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Section: Discussionmentioning

confidence: 99%

Prenatal Exposures to Common Phthalates and Prevalent Phthalate Alternatives and Infant DNA Methylation at Birth

et al. 2022

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“…To further investigate the effect of USP7 overexpression at an early developmental age on behavioral performance, we delivered AAV USP7 into the lateral ventricle of mice at P0 and conducted behavior tests at their adolescent ages (P30-P55). Elevated levels in self-grooming and marble burying behaviors are typical autistic-like behaviors in mice ( Nadeem et al., 2019 , 2020 ; Al-Mazroua et al., 2019 ). Indeed, apparent repetitive behaviors, such as grooming, digging, circling, and jumping, were observed in the USP7 mice.…”

Section: Discussionmentioning

confidence: 99%

Role of the DUB enzyme USP7 in dendritic arborization, neuronal migration, and autistic-like behaviors in mice

et al. 2022

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“…In addition, other studies have found that in utero exposure to dibutyl phthalate (DBP) led to abnormal proliferation of testicular Sertoli cells in prepubertal mice by modulating the ubiquitination of the key proliferation-related protein IRAK1 via the downregulation of Peli2 46 . Several studies have shown that phthalate exposure was associated with numerous enriched inflammatory pathways (e.g., NF-κB, MAPK, TNF-β) 19 , 47 . In our study, these pathways were not significantly associated with phthalate exposure in late pregnancy or phthalate levels in cord blood.…”

Section: Discussionmentioning

confidence: 99%

Prenatal phthalate exposure and cord blood DNA methylation

Joo-Ah

Kim

Zinia

et al. 2023

Sci Rep

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Exposure to phthalates has been shown to impede the human endocrine system, resulting in deleterious effects on pregnant women and their children. Phthalates modify DNA methylation patterns in infant cord blood. We examined the association between prenatal phthalate exposure and DNA methylation patterns in cord blood in a Korean birth cohort. Phthalate levels were measured in 274 maternal urine samples obtained during late pregnancy and 102 neonatal urine samples obtained at birth, and DNA methylation levels were measured in cord blood samples. For each infant in the cohort, associations between CpG methylation and both maternal and neonate phthalate levels were analyzed using linear mixed models. The results were combined with those from a meta-analysis of the levels of phthalates in maternal and neonatal urine samples, which were also analyzed for MEOHP, MEHHP, MnBP, and DEHP. This meta-analysis revealed significant associations between the methylation levels of CpG sites near the CHN2 and CUL3 genes, which were also associated with MEOHP and MnBP in neonatal urine. When the data were stratified by the sex of the infant, MnBP concentration was found to be associated with one CpG site near the OR2A2 and MEGF11 genes in female infants. In contrast, the concentrations of the three maternal phthalates showed no significant association with CpG site methylation. Furthermore, the data identified distinct differentially methylated regions in maternal and neonatal urine samples following exposure to phthalates. The CpGs with methylation levels that were positively associated with phthalate levels (particularly MEOHP and MnBP) were found to be enriched genes and related pathways. These results indicate that prenatal phthalate exposure is significantly associated with DNA methylation at multiple CpG sites. These alterations in DNA methylation may serve as biomarkers of maternal exposure to phthalates in infants and are potential candidates for investigating the mechanisms by which phthalates impact maternal and neonatal health.

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Ubiquitous plasticizer, Di-(2-ethylhexyl) phthalate enhances existing inflammatory profile in monocytes of children with autism

Cited by 26 publications

References 53 publications

Prenatal Exposures to Common Phthalates and Prevalent Phthalate Alternatives and Infant DNA Methylation at Birth

Prenatal Exposures to Common Phthalates and Prevalent Phthalate Alternatives and Infant DNA Methylation at Birth

Role of the DUB enzyme USP7 in dendritic arborization, neuronal migration, and autistic-like behaviors in mice

Prenatal phthalate exposure and cord blood DNA methylation

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