Deciphering the intricacies of chlorantraniliprole, azadirachtin and uniconazole interactions with fall armyworm in maize: a comprehensive analysis through transcriptomic and metabolomic profiling

Abstract BACKGROUND Maize is a critically important world staple food, yet its productivity is exposed to a notorious invasive pest of the fall armyworm ( Spodoptera frugiperda ). To discern the transgenerational effects and potential pest control efficacy, we evaluated chlorantraniliprole, azadirachtin, and uniconazole on S. frugiperda development, reproduction, metabolome, and larval transcriptome. RESULTS Exposure to chlorantraniliprole, azadirachtin, and uniconazole has impacted S. frugiperda larval development, pupation, fecundity, and longevity. Biochemical analysis of the specific enzyme activities [acetylcholinesterase (AChE), carboxylesterase (CarE), glutathione‐S‐transferase (GST), and cytochrome P450 (P450)] showed a very high magnitude of activity changes. Chlorantraniliprole and azadirachtin had prominent influences on the expression of common genes involved in DNA replication, oxidative phosphorylation, digestion, immune reaction, and the endocrine system, as shown by RNA sequencing. In contrast, uniconazole affected gene regulation only marginally. Besides, the pesticides significantly affected the maize plants by altering their metabolome and transcriptome profiles and dramatically enhanced plant mortality, especially after chlorantraniliprole and azadirachtin treatments. RNA sequencing of maize plants treated with chlorantraniliprole, azadirachtin, and uniconazole revealed significant gene expression changes, providing insights into the plant's adaptive responses and potential alterations in insect–plant interactions. CONCLUSION These results indicate complex, transgenerational effects of S. frugiperda itself and maize plants. These findings underline the potential of integrating these compounds into bio‐intensive pest management strategies against S. frugiperda , with implications for enhancing maize protection. © 2025 Society of Chemical Industry.