Early Life PBDE Flame Retardant Exposures Cause Neurobehavioral Alterations in Fish That Persist into Adulthood and Vary by Sex and Route of Exposure

Early life stages are particularly vulnerable to environmental pollutants, and many marine species develop in nearshore habitats where contaminants like polybrominated diphenyl ethers (PBDE) are common. PBDEs disrupt neurodevelopment, but their long-term effects and the influence of exposure route remain poorly understood. Using <i>Fundulus heteroclitus</i> (mummichogs), we tested whether early life exposure to BDE-99, a prevalent PBDE, leads to persistent behavioral and molecular alterations and whether outcomes differ between progenitor (maternal) exposure and direct embryonic exposure. Both approaches achieved comparable doses and were followed by rearing in clean water until adulthood. Both exposure routes resulted in long-term hyperactivity and reduced anxiety-like behavior, though effects varied by dose and sex. Progenitor exposure altered behavior and the brain transcriptome in F1 males (females not tested), whereas direct embryonic exposure affected females and not males. These findings suggest maternal factors, such as metabolites, lipid provisioning, small molecules, and epigenetic imprinting, play a key role in modulating developmental outcomes. Our results demonstrate that exposure route significantly influences long-term toxicity and highlight the importance of considering maternal contributions when assessing risks from persistent pollutants. Given that maternal and environmental exposures co-occur in nature, integrated assessments are critical for understanding real-world impacts of persistent pollutants on marine life.