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

Abstract

BackgroundThe 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.ResultsHere, 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.ConclusionsMaternal 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.Graphical