The disruption of human trophoblast functions by autophagy activation through PI3K/AKT/mTOR pathway induced by exposure to titanium carbide (Ti3C2) MXene

作者全名："Yang, Limei; Hu, Le; Tang, Hongyu; Chen, Xuemei; Liu, Xueqing; Zhang, Yue; Wen, Yixian; Yang, Yongxiu; Geng, Yanqing"

作者地址："[Yang, Limei; Chen, Xuemei; Liu, Xueqing; Wen, Yixian] Chongqing Med Univ, Sch Publ Hlth & Management, Chongqing, Peoples R China; [Yang, Limei; Tang, Hongyu; Chen, Xuemei; Liu, Xueqing; Zhang, Yue; Wen, Yixian; Geng, Yanqing] Chongqing Med Univ, Joint Int Res Lab Reprod & Dev, Chongqing, Peoples R China; [Hu, Le; Yang, Yongxiu] First Hosp Lanzhou Univ, Dept Obstet & Gynecol, Key Lab Gynecol Oncol Gansu Prov, Lanzhou, Peoples R China; [Tang, Hongyu; Zhang, Yue; Geng, Yanqing] Chongqing Med Univ, Coll Basic Med, Chongqing, Peoples R China; [Geng, Yanqing] Chongqing Med Univ, Box 197,1 Yi Xue Yuan Rd, Chongqing 400016, Peoples R China"

通信作者："Geng, YQ (通讯作者)，Chongqing Med Univ, Joint Int Res Lab Reprod & Dev, Chongqing, Peoples R China.; Yang, YX (通讯作者)，First Hosp Lanzhou Univ, Dept Obstet & Gynecol, Key Lab Gynecol Oncol Gansu Prov, Lanzhou, Peoples R China."

来源：FOOD AND CHEMICAL TOXICOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000832779500003

JCR分区：Q1

影响因子：4.3

年份：2022

卷号：165

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Ti3C2 MXene; HTR-8/SVneo; Autophagy; Trophoblast migration; Trophoblast invasion

摘要："Ti3C2 MXene, as a novel nanomaterial, has attracted great attention due to its promising properties in biomedical applications. However, the potential effects of Ti3C2 MXene on trophoblast functions have not been investigated. Here, we found that Ti3C2 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 Ti3C2 MXene exposure affected trophoblast functions. Results showed that Ti3C2 MXene entered cells and mostly deposited in the cytoplasm, inhibiting cell migration and invasion abilities. Furthermore, we found that Ti3C2 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 Ti3C2 MXene may be mediated by autophagy activation. Our results indicated that autophagy is a key factor in eliciting HTR-8/SVneo dysfunction after Ti3C2 MXene exposure, which could therefore damage placental development. Autophagy inhibition is a potential therapeutic strategy for alleviating the placental toxicity of nanoparticles."

基金机构：National Natural Science Foundation [31801247]; Natural Science Foundation Project of CQ CSTC [cstc2019jcyj-msxmX0478]; Natural Science Foundation of Gansu [21JR1RA108]

基金资助正文："We are grateful for the financial support from the National Natural Science Foundation (No. 31801247), the Natural Science Foundation Project of CQ CSTC (No. cstc2019jcyj-msxmX0478), and the Natural Science Foundation of Gansu (No. 21JR1RA108)."