Low-Level Lead Exposure During Development Differentially Affects Neurobehavioral responses in Male and Female Mouse Offspring: A Longitudinal Study

Early life low-level lead (Pb) exposure is still an alarming child health issue. To date, animal studies

investigating the effects of low doses of Pb since early stages of life to adulthood are scarce. We investigated

in a mouse model the behavioral effects of developmental exposure to low-level Pb yielding blood levels

similar to those observed in child clinical literature. CD1 outbred mouse dams received Pb (25- or 100-ppm) via

drinking water from two weeks pre-mating until the end of lactation. Offspring of both sexes underwent a

longitudinal assessment of motor, socio-emotional, and cognitive endpoints from neonatal to adult stage. Pb

levels were determined in several matrices (blood, brain and bone) up to six months after the end of exposure.

We found that new born pups exposed to Pb have slightly altered motor patterns and reduced preference for

the nest odor. Offspring of both sexes exposed to the lowest Pb dose showed diminished interest for social

novelty stimuli as adults. Moreover, sex-dependent effects of Pb exposure were observed in the spatial

learning and memory task, where males were selectively impaired. Finally, blood, brain and bone Pb levels

were elevated in a dose dependent fashion up to six months after termination of exposure. We observed

marked accumulation of Pb in bones, with higher Pb levels in 100-ppm exposed females than in males at 7

months of age. In conclusion, developmental Pb exposure caused mild alterations in early- and late-life

behavioral domains, particularly involving olfactory and cognitive responses. These findings confirm the

importance of animal models to understand how early chronic low-level lead exposure impacts on health in a

life-course perspective.