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Environ Health Perspect. 2008 Mar;116(3):355-61. doi: 10.1289/ehp.10862.

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

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1
Department of Psychology, University of Houston, Houston, Texas 77204-2020, USA.

Abstract

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, < or = 10, 24-27, and 33-42 microg/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.

KEYWORDS:

aging; amphetamine; balance; dopamine; fetal; gestation; lead; motor activity; obesity; sex

Comment in

PMID:
18335103
PMCID:
PMC2265051
DOI:
10.1289/ehp.10862
[Indexed for MEDLINE]
Free PMC Article
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