| Objective :1.To investigate whether lanthanum nitrate can pass through the placental barrier and to find the exposure biomarker correlation between pregnant rats and the offspring rats from the blood-placental barrier.2.The generation reproductive toxicity test was carried out to investigate the effect of lanthanum nitrate on humoral,cellular immune development and nonspecific immune function of offspring rats,which exposed to pregnant rats.To provide experimental basis for the daily intake of food made of rare earth elements(ADI)and risk assessment of rare earth.Methods:The developmental immunity test was carried out with reference to the standard of generation reproductive development experiment(OECD443).Healthy adult SD rats were chosen for mating according to the ratio of 1:1,40 rats were randomly divided into control group,low dose group,middle dose group and high dose group,every group has 10 pregnant rats,from seventh to sixteenth days of pregnancy by gavage give a solution of lanthanum nitrate,doses were 0,2,20,60 mg/kg BW,the amount of gastric lavage was 10ml/kg BW.After fourth days of birth(PND4),the rats were standardized in the nest,so that the number of pups per litter was about four rats,lanthanum content in blood was tested with inductively coupled plasma mass spectrometry(ICP-MS).Every nest was chosen a male and female as the A queue,another male and female as the B queue.On fifty-second days(PND52)the A queue of 80 rats were evaluated the immune system toxicity,observed indexes contain ratio of organ and body weight,histopathological observation.Peripheral blood lymphocyte typing and serum γ-IFN,IL-2,IL-4,IL-1α,IL-10,TNF content were detected by flow cytometry.The B queue of 80 pups were detected T-dependent antigen response and lymphocytes proliferation on fifty-fifth day(PND55).During the whole experimental period,the body weight,food intake per week ofpregnant rats and offspring rats were observed and recorded.The results of the experiment were analyzed by one-way ANOVA using SPSS19.0 software,and the dose effect relationship was analyzed by BMDS software.Results:1.The weight of pregnant rats increased gradually with the prolongation of gestation time,and there was no difference between treated group and the control group at different stages of pregnancy(P>0.05).Maternal food intake and total food utilization rate of treated group had no significant difference compared with the control group(P>0.05).Pathological findings showed partial liver cell steatosis,lobular inflammatory cell infiltration,and inflammatory cell infiltration in the kidney,but there was no difference in the proportion of every group,and no obvious pathological changes were found in other organs.The birth weight of offspring rats increased rapidly,and there was no difference among the groups.After weaning,the weekly food intake of treated group had no significant difference compared with the control group(P>0.05),but the high dose group of female offspring rats at fifth weeks after birth,the food utilization rate was lower than the control group(P<0.05).The absolute weight and relative weight of main organs,contain liver,kidney,lung,brain,spleen and thymus of dose group were not significantly different from those of the control group(P>0.05).2.The content of Lanthanum in whole blood of three dose groups were higher than it in the control group(P<0.05);the blood lanthanum in male offspring rats of low,medium and high dose group were significantly higher than the control group(P<0.05),the blood lanthanum in female offspring of low,high dose group were higher than those in control group(P<0.05).3.The high dose group of spleen T lymphocyte proliferation ability induced by ConA was significantly higher than the control group(P<0.05).There was no difference between the experimental group and the control group of plaque forming cells(P>0.05).4.The blood NK cells of three female treated groups increased significantly compared with the control group(P<0.05),There were no difference between the experimental group and the control group of CD4/CD8 ratio,the number of T cells and B lymphocytes.5.There was no significant difference of serum cytokine levels among groups(P>0.05).6.The dose-response relationship study of T lymphocyte proliferation and NK cell showed that the BMDL was 0.21 mg/kg BW.Conclusion:1.Lanthanum can pass through the placenta barrier into the blood of their offspring rats,there was a dose effect relationship between the level of lanthanum in the newborn rats blood and maternal blood.2.Exposed to lanthanum nitrate during pregnancy can affect the cellular immune function of offspring rats,and increase the proliferation ability of T lymphocytes,but it had no effect on the proliferation of B lymphocytes;Lanthanum nitrate had no effect on humoral immune function in offspring rats.3.Exposed to lanthanum nitrate during pregnancy can affect the nonspecific immune function of offspring rats and increase the NK cells in peripheral blood.the BMDL of lanthanum nitrate was 0.21 mg/kg BW. |
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