Sublethal lambda-cyhalothrin suppresses reproductive hormone secretion through NCX3-mediated calcium depletion in...

Chemical insecticides can persist at sublethal concentrations after field application, posing reproductive risks to natural enemies. However, the mechanisms underlying insecticide-induced male reproductive toxicity remain poorly defined. Here, sublethal lambda-cyhalothrin (λ-Cy) exposure during the second larval instar severely impaired male reproduction in the lacewing Chrysoperla sinica, causing testicular enlargement, disordered spermatogenesis, accessory-gland atrophy, and reduced sperm production. Consequently, mating treated males with untreated females decreased female fecundity and egg hatchability by 42.9% and 35.0%, respectively. Mechanistically, λ-Cy induced acute larval Ca^2 + overload, upregulating the Na⁺/Ca²⁺ exchanger NCX3. Compensatory NCX3 overexpression drove excessive Ca²⁺ extrusion, leading to Ca²⁺ depletion in the corpora allata and testes during pupal and adult stages. This imbalance suppressed juvenile hormone and 20-hydroxyecdysone biosynthesis via Ca²⁺-CREB signaling. RNA interference, pharmacological assays, dual-luciferase reporter assays, and electrophoretic mobility shift assays validated this cascade. RNAi CsMet or CsEcR phenocopied λ-Cy-induced reproductive defects. These findings identify NCX3-mediated Ca²⁺ depletion as a key mechanism of pyrethroid-induced endocrine disruption and male reproductive toxicity.