Low-level human equivalent gestational lead exposure produces sex-specific motor and coordination abnormalities and late-onset obesity in year-old mice


Background. Low-level developmental lead exposure is linked to cognitive and neurological disorders in children. However, the long-term effects of gestational lead exposure (GLE) have received little attention. Objectives. Our goals were to establish a murine model of human equivalent GLE and to determine dose–response effects on body weight, motor functions, and dopamine neurochemistry in year-old offspring. Methods. We exposed female C57BL/6 mice to water containing 0, 27 (low), 55 (moderate), or 109 ppm (high) of lead from 2 weeks prior to mating, throughout gestation, and until postnatal day 10 (PN10). Maternal and litter measures, blood lead concentrations ([BPb]), and body weights were obtained throughout the experiment. Locomotor behavior in the absence and presence of amphetamine, running wheel activity, rotarod test, and dopamine utilization were examined in year-old mice. Results. Peak [BPb] were < 1, ≤ 10, 24–27, and 33–42 μg/dL in control, low-, moderate- and high-dose GLE groups at PN0–10, respectively. Year-old male but not female GLE mice exhibited late-onset obesity. Similarly, we observed male-specific decreased spontaneous motor activity, increased amphetamine-induced motor activity, and decreased rotarod performance in year-old GLE mice. Levels of dopamine and its major metabolite were altered in year-old male mice, although only forebrain utilization increased. GLE-induced alterations were consistently larger in low-dose GLE mice. Conclusions. Our novel results show that GLE produced permanent male-specific deficits. The nonmonotonic dose-dependent responses showed that low-level GLE produced the most adverse effects. These data reinforce the idea that lifetime measures of dose–response toxicant exposure should be a component of the neurotoxic risk assessment process.



Aging, Amphetamine, Balance, Dopamine, Fetal, Sex, Gestation, Lead, Motor activity, Obesity


Copyright 2008 Environmental Health Perspectives. Recommended citation: Leasure, J. Leigh, Anand Giddabasappa, Shawntay Chaney, Jerry E. Johnson, Jr., Konstantinos Pothakos, Yuen Sum Lau, and Donald A. Fox. “Low-Level Human Equivalent Gestational Lead Exposure Produces Sex-Specific Motor and Coordination Abnormalities and Late-Onset Obesity in Year-Old Mice.” Environmental Health Perspectives 116, no. 3 (2008): 355-361. doi: 10.1289/ehp.10862. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2265051/. Reproduced in accordance with licensing terms and with the author’s permission.