Maternal exposure to CeO₂NPs derails placental development through trophoblast dysfunction mediated by excessive...

The increasing use of cerium dioxide nanoparticles (CeO₂NPs) in biomedical field has attracted substantial attention about their potential risks to human health. Recent studies have shown that nanoparticles can induce placental dysfunction and even fetal abortion, but a more detailed mechanism of nanoparticles affecting placental development remains elusive.

Here, we constructed a mouse exposure model with different doses of CeO₂NPs (2.5, 4, 5, 7.5, and 10 mg kg^-1 day^-1, average particle size 3-5 nm), finding that intravenous exposure to pregnant mice with CeO₂NPs could cause abnormal placental development. Deposited nanoparticles were able to be observed in the placental trophoblast at doses of 5 and 7.5 mg kg^-1 day^-1. Diving into molecular mechanisms indicated that CeO₂NPs exposure could lead to autophagy activation in placental trophoblast. At the cellular level, exposure to CeO₂NPs inhibited the migration and invasion of HTR-8/SVneo and activated the autophagy through mammalian target of rapamycin complex1 (mTORC1) signaling pathway. Furthermore, inhibition of autophagy initiation by 3-Methyladenine (3-MA) partially restored the function of HTR-8/SVneo, while blocking autophagic flow by Chloroquine (CQ) aggravated the functional damage.

Maternal exposure to CeO₂NPs impairs placental development through trophoblast dysfunction mediated by excessive autophagy activation. These results suggested that autophagy dysfunction may be a potential mechanism for the impairment of trophoblast by CeO₂NPs exposure. As above, our findings provide insights into the toxicity mechanism to the reproductive system induced by rare-earth nanoparticles exposure.