The insecticide permethrin induces transgenerational behavioral changes linked to transcriptomic and epigenetic alterations in zebrafish (Danio rerio)

Mélanie Blanc (1, 2, 3) , Philipp Antczak (4) , Xavier Cousin (2, 3) , Christoph Grunau (5) , Nikolai Scherbak (1, 6) , Joëlle Rüegg (7) , Steffen Keiter (1)

1 Man-Technology-Environment Research Centre, School of Science and Technology
2 UMR MARBEC - MARine Biodiversity Exploitation and Conservation
3 GABI - Génétique Animale et Biologie Intégrative
4 CMMC - Centre for Molecular Medicine Cologne [Cologne]
5 IHPE - Interactions Hôtes-Pathogènes-Environnements
6 Örebro University
7 Department of Organismal Biology

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 hours postfertilization 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.

Mots clés: Transgenerational epigenetic inheritance; developmental neurotoxicity; glutamatergic signaling; DNA methylation; pesticide

Domaines: Ecotoxicologie

Mélanie Blanc, Philipp Antczak, Xavier Cousin, Christoph Grunau, Nikolai Scherbak, et al.. The insecticide permethrin induces transgenerational behavioral changes linked to transcriptomic and epigenetic alterations in zebrafish (Danio rerio). Science of the Total Environment, 2021, 779, pp.146404. ⟨10.1016/j.scitotenv.2021.146404⟩. ⟨hal-03175988⟩