title: Low-level human equivalent gestational lead exposure produces sex-specific motor and coordination abnormalities and late-onset obesity in year-old mice.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Psychology, University of Houston, Houston, Texas 77204-2020, USA.
authors.forename: J Leigh
authors.initials: JL
authors.lastname: Leasure
authors.forename: Anand
authors.initials: A
authors.lastname: Giddabasappa
authors.forename: Shawntay
authors.initials: S
authors.lastname: Chaney
authors.forename: Jerry E
authors.initials: JE
authors.lastname: Johnson
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Pothakos
authors.forename: Yuen Sum
authors.initials: YS
authors.lastname: Lau
authors.forename: Donald A
authors.initials: DA
authors.lastname: Fox
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D007855:Lead Poisoning / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects*; D009765:Obesity / Q000139:chemically induced*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D016548:Prosencephalon / Q000378:metabolism; D012737:Sex Factors; D013997:Time Factors
chemical_list: D004298:Dopamine