Maternal exposure to CeONPs during early pregnancy impairs pregnancy by inducing placental abnormalities.

Cerium dioxide nanoparticles (CeONPs) has been widely used in many fields, and also recommended as a promising carrier for cancer targeted drugs in human medicine for its excellent properties. However, its biological safety to human health remains controversial. In this study, we propose a mouse model exposed to CeONPs during early pregnancy, to clarify the effect of maternal CeONPs exposure and related molecular mechanism. Pregnant mice are injected intravenously with CeONPs by once a day on D5, D6, and D7. The effects of CeONPs exposure on pregnancy outcomes are observed on D8, D9, D10 and D12. The results show that CeONPs exposure during early pregnancy would lead to poor pregnancy outcomes. Further study find that low-quality decidualization, including the imbalance of trophoblast invasion regulators secreted by decidual cells and abnormal recruitment and differentiation of uNK cells, leads to subsequent biological negative "ripple effects", including placental dysfunction, fetal loss or growth restriction. This study broadens the understanding of the biological safety of CeONPs, and provide clues for the prevention of its negative biological effects. Improving the function of uNK cells can be used as one of the therapeutic targets to prevent negative effects of CeONPs on pregnancy.