Although acetamiprid causes testicular toxicity in non-target animals, its low-dose toxicity mechanisms remain poorly understood, leading to underestimated ecological risks. This study demonstrates that low-dose acetamiprid exposure causes testicular toxicity by disrupting lipophagic homeostasis. Even at 0.07 mg/kg, acetamiprid induced significant testicular impairment, characterized by seminiferous epithelial disruption and excessive lipid droplet (LD) accumulation. Cellular analyses identified Sertoli cells as the primary targets, leading to severe lipotoxicity. Mechanistically, acetamiprid activated the PI3K/AKT/mTOR signaling pathway, thereby impairing lipophagic flux. The impairment was induced by increased LD diameter and p62 accumulation, which hindered LD degradation. Furthermore, the upstream initiator TLR4 facilitated extracellular signal transduction to mTOR. By elucidating these mechanisms, this study highlights the reproductive risks of acetamiprid to non-target mammals, supporting ecological risk assessment and environmental management in agricultural ecosystems.
He et al. (2026) studied this question.