IMPACT OF EARLY-LIFE ENVIRONMENTAL INHALATION EXPOSURE TO PYRETHROIDS DURING THE PERINATAL PERIOD ON NEURODEVELOPMENTAL OUTCOMES

Human epidemiological studies indicate that perinatal exposure to air pollutants, including pesticides, increases the risk of neurodevelopmental disorders (NDDs) such as autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD). However, critical windows of neurodevelopmental exposure and pathophysiological mechanisms are poorly understood. In Europe, human exposure to insecticides is unavoidable due to widespread agricultural and household use, as well as urban fumigation campaigns against invasive tiger mosquitoes. Pyrethroids, particularly deltamethrin, are among the most frequently detected insecticides in outdoor and indoor air. We modeled human-relevant pyrethroid exposure in pregnant mice, considering realistic doses, inhalation route administration, and different exposure periods. We hypothesize that certain windows of maternal exposure alter the neurodevelopment of offspring through impairment of GABAergic signaling. Offspring development was tracked from postnatal day 3 through adulthood using developmental milestones and a battery of behavioral assays combined with AI-assisted analyses. Early developmental delays and subtle adult cognitive deficits were observed. Molecular analyses revealed hormonal alterations and increases in meningeal inflammatory markers. In addition, we examined the effects of chronic exposure to deltamethrin during pregnancy on the maturation of hippocampal networks in offspring and demonstrated that deltamethrin modulates neuronal excitability via activity-dependent outgoing currents. Together, these findings indicate that chronic perinatal deltamethrin exposure disrupts early sensorimotor development and induces lasting, specific behavioral alterations. This supports the existence of critical developmental windows during which environmental exposure increases vulnerability, highlighting the importance of identifying sensitive periods to understand ASD/ADHD risk factors and inform prevention strategies.