Size-dependent maternal-fetal transfer and fetal developmental toxicity of ZnO nanoparticles after oral exposures in pregnant mice.

The widespread application of nanomaterial-based products has caused safety concerns worldwide, especially for susceptible pregnant population. Here, we revealed the effect of the size of ZnO nanoparticles (ZnO NPs) on placental and fetal developmental toxicities. We found that smaller ZnO NPs (13 nm) were able to cross both the intestinal barrier and the placental barrier to reach the fetus after oral exposure and caused fetal developmental toxicity. However, larger ZnO NPs (57 nm) and bulk ZnO particles were not able to cross these barriers and exert effects. We also discovered that the organogenesis period (GD7-GD16) was more vulnerable to such toxicity compared with the peri-implantation period (GD1-GD10) of pregnancy. This new understanding that smaller nanoparticles may pass through multiple biological barriers to induce toxicity in susceptible populations is crucial for the safeguarding of humans from the widespread application of nanoproducts. The discovery that the organogenesis stage in pregnancy is more vulnerable to nanotoxicity than the peri-implantation stage is provides valuable guidance for an improved protection strategy.