Paternal Glufosinate Ammonium Exposure Leads to Memory Dysfunction in Offspring Mice

BACKGROUND: Glufosinate ammonium (GLA) is a widely used herbicide, yet potential neurodevelopmental risks related to paternal exposure before conception remain insufficiently defined. METHODS: In this study, adult male C57BL/6J mice received GLA at 0.2 mg/kg·day for 10 consecutive weeks and were then mated with unexposed females to generate F1 offspring. Offspring growth was monitored, and neurobehavior was assessed at 5 weeks of age. RESULTS: In behavioral tests, female offspring showed reduced social novelty preference in the three-chamber test and impaired spatial learning and memory in the Morris water maze test, while open field, elevated plus maze, and rotarod performance were not altered. Male offspring showed no clear group differences in these memory-related endpoints. Golgi staining revealed reduced dendritic complexity and spine density in the hippocampus and prefrontal cortex. Glial markers were elevated, and neuronal marker changes showed region-dependent shifts. TUNEL staining indicated increased apoptosis during embryonic development and persistent apoptotic signals in the juvenile prefrontal cortex, accompanied by cytokine imbalance with increased IL-1β and decreased IL-10 in the hippocampus. CONCLUSION: These results suggest that paternal preconception GLA exposure is associated with selective memory-related behavioral deficits in juvenile offspring and with convergent glial, inflammatory, and apoptosis-related brain changes. These findings support the consideration of paternal exposure in developmental risk assessment frameworks.