Abstract: Objective · To explore whether prenatal stress can enhance the accumulation of blood/bone lead in the offspring on the basis of prenatal lead exposure, and to compare the effects of prenatal single exposures to stress/lead and prenatal combined exposure to lead and stress on fear-conditioning memory in the offspring. Methods · Pregnant rats were randomly divided into control group, stress exposure group, lead exposure group and combined lead-stress exposure group. After delivery, each group contained twelve pups (male:female1:1). The extinction process of fear-conditioning memory was evaluatedthe fear-conditioning test in the offspring at 3 weeks old. The offspring were then sacrificed at 4 weeks old. Blood and tibia samples were collected, blood lead was measuredusing the atomic absorption spectrometer, and tibia lead was measuredusing the inductively coupled plasma–mass spectrometry. The levels of blood lead, bone lead and fear memory were comparedanalysis of variance, and the relationship between blood lead, bone lead and fear memory were analyzedLogistic regression model. Results · The levels of blood and bone lead in the lead exposure group (P blood lead0.013, P bone lead0.000) and combined exposure group (P blood lead0.000, P bone lead0.000) were significantly higher than those in the control group; the level of blood lead in the stress group was higher but not significantly different that in the control group (P blood lead0.056) and the level of bone lead in the stress group was significantly higher than that in the control group (P bone lead0.004); the levels of blood and bone lead in combined exposure group were higher than those in the lead exposure group, but the differences didn’t reach statistical significance (P blood lead0.682, P bone lead0.124). Compared with young rats in the lowest blood lead/bone lead groups, young rats in the groups of higher blood/bone lead levels had higher odds ratios of high fear reaction during the second (P0.008/ P0.016) and the third (P0.019/P0.005) time periods. The ratios of freezing time in the first [(83.73±25.47)%] and the second [(92.97±15.75)%] periods of the fear-conditioning test in the combined exposure group were significantly higher than those in the control group [the first period, (65.35±28.80)%, P10.048; the second period, (68.78±27.22)%, P20.021]. Conclusion · Compared with the single exposure to lead during pregnancy, maternal gestation combined exposure to lead and stress may induce more increases in the blood and bone lead levels in the offspring. Lead exposure during pregnancy may inhibit the process of the extinction of fear memory in the offspring, and this effect may be aggravatedprenatal concurrent exposure to stress.

Key words: prenatal stress, lead exposure, combined lead-stress exposure, fear-conditioning memory