Yang Limei, Hu Le, Tang Hongyu, Chen Xuemei, Liu Xueqing, Zhang Yue, Wen Yixian, Yang Yongxiu, Geng Yanqing
School of Public Health and Management, Chongqing Medical University, Chongqing, China; Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, China.
Department of Obstetrics and Gynecology, The First Hospital of Lanzhou University, Key Laboratory of Gynecologic Oncology of Gansu Province, Lanzhou, China.
Food Chem Toxicol. 2022 Jul;165:113128. doi: 10.1016/j.fct.2022.113128. Epub 2022 May 12.
TiC MXene, as a novel nanomaterial, has attracted great attention due to its promising properties in biomedical applications. However, the potential effects of TiC MXene on trophoblast functions have not been investigated. Here, we found that TiC MXene exposure weakened the extension ability of villus explants in vitro. We employed human trophoblast HTR-8/SVneo cells to reveal the underlying molecular mechanisms by which TiC MXene exposure affected trophoblast functions. Results showed that TiC MXene entered cells and mostly deposited in the cytoplasm, inhibiting cell migration and invasion abilities. Furthermore, we found that TiC MXene exposure elevated autophagy through the inhibition of the PI3K/AKT/mTOR pathway. Meanwhile, the application of an autophagy inhibitor (3-MA) prevented autophagy and restored cell viability, resulting in the recovery of cell migration and invasion abilities. These indicated that the cellular dysfunction induced by TiC MXene may be mediated by autophagy activation. Our results indicated that autophagy is a key factor in eliciting HTR-8/SVneo dysfunction after TiC MXene exposure, which could therefore damage placental development. Autophagy inhibition is a potential therapeutic strategy for alleviating the placental toxicity of nanoparticles.
TiC MXene作为一种新型纳米材料，因其在生物医学应用中的优异性能而备受关注。然而，TiC MXene对滋养层细胞功能的潜在影响尚未得到研究。在此，我们发现暴露于TiC MXene会削弱体外绒毛外植体的伸展能力。我们使用人滋养层HTR-8/SVneo细胞来揭示TiC MXene暴露影响滋养层细胞功能的潜在分子机制。结果表明，TiC MXene进入细胞并主要沉积在细胞质中，抑制细胞迁移和侵袭能力。此外，我们发现暴露于TiC MXene会通过抑制PI3K/AKT/mTOR途径提高自噬水平。同时，应用自噬抑制剂（3-MA）可防止自噬并恢复细胞活力，从而恢复细胞迁移和侵袭能力。这些表明TiC MXene诱导的细胞功能障碍可能由自噬激活介导。我们的结果表明，自噬是TiC MXene暴露后引发HTR-8/SVneo功能障碍的关键因素，因此可能损害胎盘发育。抑制自噬是减轻纳米颗粒胎盘毒性的潜在治疗策略。
