Maternal exposure to CeONPs derails placental development through trophoblast dysfunction mediated by excessive autophagy activation.

Background: The increasing use of cerium dioxide nanoparticles (CeONPs) 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.

Results: Here, we constructed a mouse exposure model with different doses of CeONPs (2.5, 4, 5, 7.5, and 10 mg kg day, average particle size 3-5 nm), finding that intravenous exposure to pregnant mice with CeONPs 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 day. Diving into molecular mechanisms indicated that CeONPs exposure could lead to autophagy activation in placental trophoblast. At the cellular level, exposure to CeONPs 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.

Conclusions: Maternal exposure to CeONPs 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 CeONPs exposure. As above, our findings provide insights into the toxicity mechanism to the reproductive system induced by rare-earth nanoparticles exposure.