Prenatal maternal lead exposure in experimental animals and humans produces higher incidences of fetal death and spontaneous abortion, retards fetal and postnatal growth and appears to be associated with abnormal postnatal behavioral development. However, OSHA has yet to establish a """"""""no effect"""""""" level for occupationally or environmentally exposed pregnant women. Further, no experimental animal studies have clearly defined a clear relationship between lead exposure and retarded fetal growth. This investigation will expose 100 day old pregnant rats to lead acetate via drinking water to assess the effect of maternal lead exposure on fetal and early neonatal skeletal growth. Water and food intake of the lead-exposed animals will be matched to that of the control animals. It is hypothesized that alteration of maternal calcium metabolism during pregnancy by maternal lead exposure will result in retarded skeletal growth in the offspring. In accordance to the project hypothesis, the following aims will be addressed: (a) determine whether maternal lead exposure affects primary morphometric indices of fetal skeletal growth by measurement of birth weight, crown to rump length, femoral length and tail bone ossification; (b) to quantify the effect of maternal lead exposure on early neonatal bone remodeling by measurement by dynamic histomorphometry measurement of in vivo rates of neonatal bone formation, resorption, and mineralization; (c) to assess the effect of maternal lead exposure on fetal and early neonatal bone calcium content and serum (ionized and total) levels with the use of ion- selective electrodes (ionized calcium) and flame atomic absorption (total serum and bone calcium); and (d) to investigate the biological mechanisms of bone lead toxicity in the rat. The experiments which will be designed to investigate the mechanisms of lead toxicity on bone will depend on the results obtained in (a), (b), and (c). It is proposed that these potential experiments could include an in vivo and in vitro investigation of the effect of lead on (a) hormonal calcium regulation and (b) local and systemic bone metabolism control and (c) osteoblast and osteoclast regulation. Data obtained from this proposed study will help delineate the relationship between maternal lead exposure and offspring skeletal growth retardation, and facilitate the definition of plausible mechanisms of lead effect on growing bone and calcium metabolism.
