Impact of maternal gestation combined exposure to lead and mental stress on offspring's fear-conditioning memory / 上海交通大学学报（医学版）

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 (malefemale=11). The extinction process of fear-conditioning memory was evaluated by the 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 measured by using the atomic absorption spectrometer, and tibia lead was measured by using the inductively coupled plasma-mass spectrometry. The levels of blood lead, bone lead and fear memory were compared by analysis of variance, and the relationship between blood lead, bone lead and fear memory were analyzed by Logistic regression model. Results: The levels of blood and bone lead in the lead exposure group (P blood lead=0.013, P bone lead=0.000) and combined exposure group (P blood lead=0.000, P bone lead=0.000) were significantly higher than those in the control group; the level of blood lead in the stress group was higher but not significantly different from that in the control group (P blood lead=0.056) and the level of bone lead in the stress group was significantly higher than that in the control group (P bone lead=0.004); 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 lead=0.682, P bone lead=0.124). 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 (P=0.008/P=0.016) and the third (P=0.019/P=0.005) 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)%, P1=0.048; the second period, (68.78±27.22)%, P2=0.021]. 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 aggravated by prenatal concurrent exposure to stress.