| This study implemented a pregnant guinea pig model to examine effects of lead in the fetus and dam. Pregnant guinea pigs were orally administered 0, 5.5, or 11 mg lead/kg body weight for 30 or 40 days, commencing on day 22 of gestation. This treatment regimen produced blood lead (Pb) levels that were near the currently identified "no effect" level for children (10-30 ;One proposed mechanism for underlying neurobehavioral deficits induced by low levels of Pb is impairment of neuroglial development and function. This hypothesis was examined by measuring specific activities of the astroglia marker, glutamine synthetase (GS) and the oligodendroglial marker, glycerol-3-phosphate dehydrogenase (GPDH). Pb exposure produced a significant dose-dependent decrease in GS and GPDH activity in the guinea pigs. Further studies on GS activity in cultured astroglia indicated that Pb decreases astroglia viability and inhibits GS activity by more than one mechanism.;Lead's effect on hypothalamic hormones have been implicated in delaying the onset of puberty in humans and animal models. Levels of gonadotropin-releasing hormone (GnRH), somatostatin (SRIF), and progesterone were measured in Pb-exposed guinea pigs. Pb was found to exacerbate normal decreases in GnRH and progesterone and increases in SRIF. The significance of these Pb-induced changes could not be examined due to lack of standardized radioimmunoassays for guinea pig pituitary hormones.;Another plausible mechanism for Pb's toxic effects is its ability to alter trace elements in various organs. Concentrations of Pb, copper, iron, and zinc were measured in the guinea pig's brain, liver, kidney, femur, and placenta. Lead exposure decreased iron and zinc concentrations in all organs examined. Copper concentrations were decreased by Pb in all the maternal tissues, but increased in the fetal tissues. Highest Pb levels were found in bone, followed by kidney, liver, blood, cerebellum, placenta, and forebrain.;In conclusion, this study demonstrates the pregnant guinea pig model to be adequate for chronic low-level Pb studies. |
