Breakthrough of ZrO2 nanoparticles into fetal brains depends on developmental stage of maternal placental barrier and fetal blood-brain-barrier

[Display omitted] •Oral intake of ZrO2 nanoparticles by pregnant mice caused brain accumulation of them in fetus.•They cross maternal intestinal barrier, blood-placenta-barrier, and fetal blood-brain-barrier to reach fetal brains.•The translocation of nanoparticles is partially blocked when these barriers are well developed. Ingestion of nanoparticles may cause various damages to human body. However, how such ingestion by pregnant mother influences fetal development is not known because, presumably, ingested nanoparticles have to cross multiple biological barriers (such as intestinal and placental) to reach fetus. To answer this crucial question, here we investigated how a relatively biocompatible zirconia nanoparticles (ZrO2 NPs, 16 nm) were translocated to fetal brains in three exposure models of pregnant mice: Model 1, oral exposure of nanoparticles before maternal blood-placental barrier (BPB) was fully developed; Model 2, exposures after BPB was developed, but before fetal blood-brain-barrier (BBB) was fully developed; Model 3, exposures after both maternal BPB and fetal BBB were fully developed. Our experimental results showed that translocation of ZrO2 NPs into fetal brains was 55 % higher in Model 2 and 96 % higher in Model 1 compared with that in Model 3 after nanoparticles (50 mg/kg) were orally exposed to pregnant mice. Therefore, nanoparticles are able to cross multiple biological barriers and nanotoxicity to fetus is highly dependent on stages of pregnancy and fetal development or the maturity of multiple biological barriers. Oral exposures to nanoparticles during pregnancy are dangerous to fetal brain development, especially in early pregnancy.