Effects of acetamiprid on DNA methylation, transcriptomics, and neurogenesis in human mesenchymal stem cells

Acetamiprid (ACE), a Neonicotinoid insecticides (NEOs), is highly selective for insect nicotinic acetylcholine receptors (nAChRs). However, increasing evidence of hazards was reported in mammals. We investigated the effects of ACE on both global DNA methylation and epigenetic change, transcriptomic dysregulation, and neural differentiation. ACE decreased AluYb8 methylation levels in human mesenchymal stem cells. TET2 expression was enhanced suggesting that it was involved in the active DNA demethylation caused by ACE. Global DNA methylation pattern identified 87 significant differentially methylated positions (DMPs) and transcriptomic analysis identified 385 differentially expressed genes (DEGs). Pathways related to the psychiatric system, including Alzheimer's disease and TGF-β, were significantly enriched. ACE inhibited the expression of neurogenesis marker MAP2 and SNCA, which was repressed by TETs inhibitor Bobcat339. Our results suggested that exposure to ACE disturbed DNA methylation, and resulted in the impaired neural differentiation revealed by abnormal expression of neuronal and PD-related marker protein.