PUBLICATION
The insecticide permethrin induces transgenerational behavioral changes linked to transcriptomic and epigenetic alterations in zebrafish (Danio rerio)
- Authors
- Blanc, M., Antczak, P., Cousin, X., Grunau, C., Scherbak, N., Rüegg, J., Keiter, S.H.
- ID
- ZDB-PUB-210323-17
- Date
- 2021
- Source
- The Science of the total environment 779: 146404 (Journal)
- Registered Authors
- Keywords
- DNA methylation, Developmental neurotoxicity, Glutamatergic signaling, Pesticide, Transgenerational epigenetic inheritance
- Datasets
- GEO:GSE154206, GEO:GSE154020
- MeSH Terms
-
- Animals
- Behavior, Animal
- DNA Methylation
- Epigenesis, Genetic
- Epigenomics
- Female
- Insecticides*/toxicity
- Male
- Permethrin/toxicity
- Transcriptome
- Zebrafish*/genetics
- PubMed
- 33752003 Full text @ Sci. Total Environ.
Citation
Blanc, M., Antczak, P., Cousin, X., Grunau, C., Scherbak, N., Rüegg, J., Keiter, S.H. (2021) The insecticide permethrin induces transgenerational behavioral changes linked to transcriptomic and epigenetic alterations in zebrafish (Danio rerio). The Science of the total environment. 779:146404.
Abstract
The pyrethroid insecticide permethrin is widely used for agricultural and domestic purposes. Previous data indicated that it acts as a developmental neurotoxicant and can induce transgenerational effects in non-target organisms. However, associated underlying mechanisms remain unclear. The aim of this study was to investigate permethrin-related transgenerational effects in the zebrafish model, and to identify possible molecular mechanisms underlying inheritance. Zebrafish (F0) were exposed to permethrin during early-life (2 h post-fertilization up to 28 days). The F1 and F2 offspring generations were obtained by pairing exposed F0 males and females, and were bred unexposed. Locomotor and anxiety behavior were investigated, together with transcriptomic and epigenomic (DNA methylation) changes in brains. Permethrin exposed F0 fish were hypoactive at adulthood, while males from the F1 and F2 generations showed a specific decrease in anxiety-like behavior. In F0, transcriptomic data showed enrichment in pathways related to glutamatergic synapse activity, which may partly underlie the behavioral effects. In F1 and F2 males, dysregulation of similar pathways was observed, including a subset of differentially methylated regions that were inherited from the F0 to the F2 generation and indicated stable dysregulation of glutamatergic signaling. Altogether, the present results provide novel evidence on the transgenerational neurotoxic effects of permethrin, as well as mechanistic insight: a transient exposure induces persistent transcriptional and DNA methylation changes that may translate into transgenerational alteration of glutamatergic signaling and, thus, into behavioral alterations.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping