Maternal cerium nitrate exposure induces developmental immunotoxicity in BALB/c mouse offspring

With the increasing application of cerium and rare-earth elements (REEs), cerium exposure is becoming more widespread. However, there remains a paucity of evidence on developmental immunotoxicity of cerium. This study was designed to examine the developmental immunotoxicity of gestational and postnatal exposure to cerium nitrate (CN) in BALB/C mouse offspring. Dams were given CN by oral gavage at 0, 0.002, 0.02 and 0.2 mg/kg from gestation day 5 (GD5) to postnatal day 21 (PND 21). On PND 21, the highest dose of CN significantly suppressed the NK cell cytotoxicity, and reduced the proportions of NK cells in peripheral blood and spleen of both female and male pups, however, the proportions of monocytes in peripheral blood and macrophages in spleen only increased in female pups. For adaptive immunity, on PND 21, the suppression of T/B lymphocyte proliferation, humoral and cellular immune responses (number of splenic plaque-forming cells, PFC, and delayed-type hypersensitivity, DTH) were observed in both female and male pup mice exposed to 0.2 mg/kg CN. However, the fall of proportions of T/B lymphocytes in peripheral blood (PB), spleen and mesenteric lymph node (MLN) only found in female pups at 0.2 mg/kg on PND 21. Most indications recovered to normal after 3-week cessation of CN exposure, except the reduction of DTH and PFC. From the findings in this study, the lowest-observed-adverse-effect level (LOAEL) of CN for developmental immunotoxicity was estimated to be 0.2 mg/kg bw per day.