Insights into Physiological, Reproductive, and Transgenerational Toxicity Induced by Larval Cadmium Exposure in Honeybee ( Apis mellifera ) Queens

Cadmium (Cd), a pervasive heavy metal and potent environmental contaminant, threatens ecosystem integrity, yet its impacts on pollinating insects remain insufficiently characterized. In this study, we systematically investigated the consequences of larval-stage Cd exposure on honeybee (Apis mellifera) queens through integrated physiological, metabolomic, and proteomic analyses. Sublethal Cd exposure disrupted hormone balance, induced midgut epithelial degeneration, and impaired hemolymph lipid homeostasis, collectively retarding queen developmental progression and physiological maturation. Ovarian proteomic profiling further revealed the Cd-mediated suppression of key proteins involved in muscle contraction, tracheal function, neural conduction, and antioxidant defense, ultimately leading to diminished reproductive vitality. Critically, high-dose Cd exposure elicited transgenerational impairments: F1 workers showed reduced body size, lowered sucrose responsiveness, and impaired olfactory learning, while F1 queens developed smaller ovaries with fewer ovarioles. Together, these results demonstrate that Cd imposes substantial multigenerational fitness costs on honeybee colonies via both direct physiological impairment and transgenerational toxicity. Our findings underscore the urgency of mitigating environmental Cd pollution to protect pollinator health and ensure sustainable ecosystems.