Gene–Environment Interactions in Developmental Neurotoxicity: a Case Study of Synergy between Chlorpyrifos and CHD8 Knockout in Human BrainSpheres
Sergio Modafferi, Xiali Zhong, André Kleensang, Yohei Murata, Francesca Fagiani, David Pamies, Helena T. Högberg, Vittorio Calabrese, Herbert M. Lachman, Thomas Härtung, Lena Smirnova
Abstract
BACKGROUND: ) interactions. OBJECTIVES: ) and environmental exposure to an organophosphate pesticide (chlorpyrifos; CPF) in an iPSC-derived human three-dimensional (3D) brain model. METHODS: and exposed to CPF or its oxon-metabolite (CPO). Neural differentiation, viability, oxidative stress, and neurite outgrowth were assessed, and levels of main neurotransmitters and selected metabolites were validated against human data on ASD metabolic derangements. RESULTS: in BrainSpheres led to an imbalance of excitatory/inhibitory neurotransmitters and lower levels of dopamine. DISCUSSION: ) interaction in ASD. https://doi.org/10.1289/EHP8580.