Exposure to two-dimensional ultrathin Ti3C2 (MXene) nanosheets during early pregnancy impairs neurodevelopment of offspring in mice

Background Two-dimensional ultrathin Ti.sub.3C.sub.2 (MXene) nanosheets have been extensively explored for various biomedical applications. However, safety issues and the effects of Ti.sub.3C.sub.2 on human health remain poorly understood. Results To explore the influence on foetal or offspring after exposure to Ti.sub.3C.sub.2 nanosheets, we established a mouse model exposed to different doses of Ti.sub.3C.sub.2 nanosheets during early pregnancy in this study. We found that Ti.sub.3C.sub.2 nanosheets had negligible effect on the reproductive ability of maternal mice, including average pregnancy days, number of new-borns, and neonatal weight, etc. Unexpectedly, abnormal neurobehavior and pathological changes in the cerebral hippocampus and cortex in adult offspring were observed following Ti.sub.3C.sub.2 nanosheet treatment. In further studies, it was found that Ti.sub.3C.sub.2 exposure led to developmental and functional defects in the placenta, including reduced area of labyrinth, disordered secretion of placental hormones, and metabolic function derailment. The long-chain unsaturated fatty acids were significantly higher in the placenta after Ti.sub.3C.sub.2 exposure, especially docosahexaenoic acid (DHA) and linoleic acid. The metabolic pathway analysis showed that biosynthesis of unsaturated fatty acids was upregulated while linoleic acid metabolism was downregulated. Conclusions These developmental and functional defects, particularly metabolic function derailment in placenta may be the cause for the neuropathology in the offspring. This is the first report about the effects of Ti.sub.3C.sub.2 nanosheet exposure on pregnancy and offspring. The data provides a better understanding of Ti.sub.3C.sub.2 nanosheets safety. It is suggested that future studies should pay more attention to the long-term effects of nanomaterials exposure, including the health of offspring in adulthood, rather than only focus on short-term effects, such as pregnancy outcomes. Metabolomics could provide clues for finding the prevention targets of the biological negative effect of Ti.sub.3C.sub.2 nanosheets. Graphical Keywords: Reproductive fitness, Offspring health, Biosafety, Environmental factors, Ti.sub.3C.sub.2 nanosheets, Neurotoxic