Parental Lead Exposure Induces Multigenerational Deficits in Survival, Body Weight, Locomotion, and Reproductive Fitness in Drosophila melanogaster

Background: Lead (Pb) remains a pervasive environmental contaminant with the potential to induce long-lasting biological harm, yet its heritable effects across generations are not fully understood. Aim: This study investigated the transgenerational consequences of chronic dietary Pb exposure in Drosophila melanogaster across four generations (F0–F3), focusing on survival, body weight, locomotor performance, fecundity, egg-to-adult viability, and eclosion success. Methods: Wild-type W1118 strain of flies were exposed to 500 ppm Pb for 20 days, and offspring from paternal, maternal, and combined exposure lineages were evaluated under Pb-free conditions. Results: Body weight and negative geotaxis assays revealed significant body weight and locomotor impairments in Pb-exposed F0 flies (P < 0.0001), persisting strongly in F1 (P < 0.0001), partially in F2, and resolving by F3. Survival analyses showed markedly reduced lifespan in exposed F0 flies (P < 0.0001) and sustained intergenerational deficits in F1 (P < 0.0001) and F2, with the F3 generation partially recovering yet remaining lower than controls. Reproductive assessments revealed significant declines in fecundity and egg-to-adult viability across Pb-lineage descendants, particularly in combined exposure groups (P < 0.0001). Eclosion rates were also reduced in exposed lineages across all generations (P < 0.0001), with developmental delays most pronounced under combined parental exposure. Conclusion: Pb exposure causes heritable physiological and developmental defects that persist up to the F3 generation, potentially mediated by epigenetic alterations, oxidative stress, or germline effects, highlighting long-term risks and validating Drosophila melanogaster as a model for studying multigenerational toxicity.