Joint International Research Laboratory of Reproductive and Development, Department of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Box 197, No. 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, People's Republic of China.
Department of Obstetrics and Gynecology, Key Laboratory of Gynecologic Oncology of Gansu Province, The First Hospital of Lanzhou University, No. 1 West Donggang Road, Chengguan District, Lanzhou, Gansu, 730000, People's Republic of China.
J Nanobiotechnology. 2022 Mar 5;20(1):108. doi: 10.1186/s12951-022-01313-z.
Two-dimensional ultrathin TiC (MXene) nanosheets have been extensively explored for various biomedical applications. However, safety issues and the effects of TiC on human health remain poorly understood.
To explore the influence on foetal or offspring after exposure to TiC nanosheets, we established a mouse model exposed to different doses of TiC nanosheets during early pregnancy in this study. We found that TiC 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 TiC nanosheet treatment. In further studies, it was found that TiC 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 TiC 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.
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 TiC nanosheet exposure on pregnancy and offspring. The data provides a better understanding of TiC 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 TiC nanosheets.
二维超薄 TiC（MXene）纳米片已被广泛探索用于各种生物医学应用。然而，TiC 对人体健康的安全性问题和影响仍知之甚少。
为了研究暴露于 TiC 纳米片后对胎儿或后代的影响，我们在本研究中建立了一个在孕早期暴露于不同剂量 TiC 纳米片的小鼠模型。我们发现 TiC 纳米片对母鼠的生殖能力几乎没有影响，包括平均妊娠天数、新生鼠数量和新生鼠体重等。出乎意料的是，TiC 纳米片处理后成年后代的神经行为异常和大脑海马体及皮质的病理变化。在进一步的研究中，发现 TiC 暴露导致胎盘发育和功能缺陷，包括迷路面积减少、胎盘激素分泌紊乱和代谢功能失调。TiC 暴露后胎盘长链不饱和脂肪酸显著升高，尤其是二十二碳六烯酸（DHA）和亚油酸。代谢通路分析显示，不饱和脂肪酸的生物合成上调，而亚油酸代谢下调。
这些发育和功能缺陷，特别是胎盘代谢功能失调，可能是后代神经病理学的原因。这是第一篇关于 TiC 纳米片暴露对妊娠和后代影响的报告。该数据提供了对 TiC 纳米片安全性的更好理解。建议未来的研究应更加关注纳米材料暴露的长期影响，包括成年后代的健康，而不仅仅关注短期影响，如妊娠结局。代谢组学可以为寻找 TiC 纳米片生物负性效应的预防靶点提供线索。
