Paternal glufosinate exposure alters early embryonic inflammatory signals and offspring neurobehavior in IVF-derived mice.

PURPOSE: Glufosinate (GLA) is a widely used herbicide, but developmental risks from paternal preconception exposure are unclear. We tested whether paternal GLA exposure affects offspring neurobehavior via fertilization-stage transmission using IVF. RESULTS: Male mice received GLA (0.2 mg/kg·day) for 10 weeks, and sperm were used for IVF with unexposed oocytes. Female offspring at 5 weeks showed reduced social novelty preference and slower Morris water maze navigation, with no probe difference. In brain, glial markers increased and GAD1 altered regionally. In preimplantation embryos, CCL3 and CCL4 were elevated at two-cell and four-cell stages, weakening by eight-cell; fetal brains showed a pro-inflammatory shift (higher IL-1β, lower IL-10) at E14.5/E17.5. Six inflammation-associated miRNAs were mostly reduced in sperm. Zygote injection of miRNA mimic mixture partially restored social and maze performance and reduced CCL3/CCL4 signals. CONCLUSIONS: These findings provide evidence that paternal GLA exposure is associated with early embryonic inflammatory signals and offspring neurobehavioral changes, supporting inclusion of paternal exposure in developmental neurotoxicity assessment.