PUBLICATION
Perinatal exposure to potential endocrine disrupting chemicals and autism spectrum disorder: From Norwegian birth cohort to zebrafish studies
- Authors
- Desalegn, A.A., van der Ent, W., Lenters, V., Iszatt, N., Stigum, H., Lyche, J.L., Berg, V., Kirstein-Smardzewska, K.J., Esguerra, C.V., Eggesbø, M.
- ID
- ZDB-PUB-231026-54
- Date
- 2023
- Source
- Environment International 181: 108271108271 (Journal)
- Registered Authors
- Esguerra, Camila V., Kirstein-Smardzewska, Karolina Joanna, van der Ent, Wietske
- Keywords
- Autism spectrum disorder, Endocrine disrupting chemicals, Pesticides, Prospective birth cohort study, Zebrafish larvae, β-HCH
- MeSH Terms
-
- Animals
- Autism Spectrum Disorder*/chemically induced
- Autism Spectrum Disorder*/epidemiology
- Birth Cohort
- Endocrine Disruptors*/toxicity
- Environmental Pollutants*/analysis
- Environmental Pollutants*/toxicity
- Female
- Humans
- Norway/epidemiology
- Pregnancy
- Prospective Studies
- Zebrafish
- PubMed
- 37879205 Full text @ Environ. Int.
Citation
Desalegn, A.A., van der Ent, W., Lenters, V., Iszatt, N., Stigum, H., Lyche, J.L., Berg, V., Kirstein-Smardzewska, K.J., Esguerra, C.V., Eggesbø, M. (2023) Perinatal exposure to potential endocrine disrupting chemicals and autism spectrum disorder: From Norwegian birth cohort to zebrafish studies. Environment International. 181:108271108271.
Abstract
Background The etiology of autism spectrum disorder (ASD) is multifactorial, involving genetic and environmental contributors such as endocrine-disrupting chemicals (EDCs).
Objective To evaluate the association between perinatal exposure to 27 potential EDCs and ASD among Norwegian children, and to further examine the neurodevelopmental toxicity of associated chemicals using zebrafish embryos and larvae.
Method 1,199 mothers enrolled in the prospective birth-cohort (HUMIS, 2002-2009) study. Breastmilk levels of 27 chemicals were measured: polychlorinated biphenyls, organochlorine pesticides, polybrominated diphenyl ethers, and perfluoroalkyl substances as a proxy for perinatal exposure. We employed multivariable logistic regression to determine association, utilized elastic net logistic regression as variable selection method, and conducted an in vivo study with zebrafish larvae to confirm the neurodevelopmental effect.
Results A total of 20 children had specialist confirmed diagnosis of autism among 1,199 mother-child pairs in this study. β-Hexachlorocyclohexane (β-HCH) was the only chemical associated with ASD, after adjusting for 26 other chemicals. Mothers with the highest levels of β-HCH in their milk had a significant increased risk of having a child with ASD (OR = 1.82, 95 % CI: 1.20, 2.77 for an interquartile range increase in ln-transformed β-HCH concentration). The median concentration of β-HCH in breast milk was 4.37 ng/g lipid (interquartile range: 2.92-6.47), and the estimated daily intake (EDI) for Norwegian children through breastfeeding was 0.03 µg/kg of body weight. The neurodevelopmental and social behavioral effects of β-HCH were established in zebrafish embryos and larvae across various concentrations, with further analysis suggesting that perturbation of dopaminergic neuron development may underlie the neurotoxicity associated with β-HCH.
Conclusions Prenatal exposure to β-HCH was associated with an increased risk of specialist-confirmed diagnoses of ASD among Norwegian children, and the EDI surpasses the established threshold. Zebrafish experiments confirm β-HCH neurotoxicity, suggesting dopaminergic neuron disruption as a potential underlying mechanism.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping