Gene–Environment Interactions in Developmental Neurotoxicity: a Case Study of Synergy between Chlorpyrifos and CHD8 Knockout in Human BrainSpheres

Abstract

This study pioneered (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>G</mml:mi><mml:mo>×</mml:mo><mml:mi>E</mml:mi></mml:mrow></mml:math>) interaction in iPSC-derived organoids. The experimental strategy enables biomonitoring and environmental risk assessment for ASD. Our findings reflected some metabolic perturbations and disruption of neurotransmitter systems involved in ASD. The increased susceptibility of <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mtext>CHD</mml:mtext><mml:msup><mml:mrow><mml:mn>8</mml:mn></mml:mrow><mml:mrow><mml:mrow><mml:mo>+</mml:mo><mml:mo>/</mml:mo><mml:mo>-</mml:mo></mml:mrow></mml:mrow></mml:msup></mml:mrow></mml:math> BrainSpheres to chemical insult establishes a possibly broader role of (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>G</mml:mi><mml:mo>×</mml:mo><mml:mi>E</mml:mi></mml:mrow></mml:math>) interaction in ASD. https://doi.org/10.1289/EHP8580.