DEVELOPMENTAL EXPOSITION TO FUNGICIDES INDUCES AUTISTIC-LIKE BEHAVIOR IN MICE

Human populations are exposed to multiple chemical pollutants that may adversely affect brain development; however, the underlying mechanisms and critical windows of vulnerability remain poorly understood. Here, we investigated the effects of a fungicide cocktail on behavioral outcomes and gene expression across postnatal development. Female mice were exposed during gestation and/or lactation to a mixture of three anilinopyrimidines (cyprodinil, mepanipyrim, and pyrimethanil) in drinking water at the maximum concentration authorized in Europe (0.1 µg/L). Developmental milestones in the offspring were assessed, followed by the evaluation of social and motor behaviors up to adulthood. Perinatal exposure to the fungicide cocktail disrupted developmental trajectories and induced long-lasting social and motor deficits, with more pronounced effects following postnatal exposure through lactation. To explore the molecular mechanisms underlying these autistic-like behaviors, we performed RNA sequencing in juvenile mice and further analyzed the expression of selected candidate genes at different developmental stages. Notably, anilinopyrimidines altered the expression of key regulators of brain development and social behavior, including GPCRs. Our findings suggest that early-life exposure to fungicides may alter critical periods of behavioral development by targeting GPCR-mediated neuromodulation. Overall, this work is part of a broader project aimed at evaluating how the developmental exposome may alter susceptibility to neurodegenerative diseases later in life.