Oral intake of ZrO2 nanoparticles by pregnant mice results in nanoparticles' deposition in fetal brains

Nanotoxicity to fetal brains after maternal oral exposures during pregnancy is often in question because nanoparticles have to cross multiple biological barriers such as intestinal barrier, maternal blood placental barrier (BPB) and fetal blood brain barrier (BBB). Here, we investigated this seemingly impossible passage for ZrO2 nanoparticles (ZrO2 NPs) from maternal body to fetal brains using a pregnant mouse model. After three oral exposures to pregnant mice at late pregnancy (GD16, 17, 18), ZrO2 NPs were able to accumulate in fetal brains at GD19 via crossing the well-developed maternal BPB and fetal BBB. Moreover, ZrO2 NPs crossed the mature biological barriers with increasing the expression levels of caveolae, clathrin and arf6 proteins as well as decreasing the expression levels of the tight junction proteins claudin-5, occludin and ZO-1 in placenta and fetal brain. From this investigation, we speculated that the main mechanisms for such translocation were receptor mediated endocytosis transcellular pathway and breakthrough of tight junctions paracellular pathway in mature maternal BPB and fetal BBB. These findings have important implications for other nanoparticles exposures during pregnancy and provide crucial information to safeguard fetal development from contamination of widely used nanoproducts.