Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China.
Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China; Heifei Center for Disease Control and Prevention, Hefei, Anhui, China.
Ecotoxicol Environ Saf. 2022 Dec 15;248:114288. doi: 10.1016/j.ecoenv.2022.114288. Epub 2022 Nov 11.
1-nitropyrene (1-NP) is representative nitropolycyclic aromatic hydrocarbon pollutant widely present in exhaust particles of internal combustion engine, which is known for its carcinogenicity and mutagenicity. Previous studies have demonstrated that 1-NP has reproductive toxicity, but the specific mechanism is unknown. In this study, Human decidual stromal cells (HDSCs) were treated by 1-NP, exosomes were extracted from the conditioned medium of HDSCs, which were then used to treat human chorionic trophoblast cells (HTR8/SVneo) for 24 h. The findings showed that human decidual stromal cell-derived exosomes (HDSC-EXOs) can promote the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT; Vimentin and N-cadherin) of HTR8/SVneo by about 64%, 17%, 23%, 81% and 13%. The process of regulating the biological behaviors of embryonic trophoblast cells by maternal decidual stromal cells during pregnancy was simulated. Further investigations showed that HDSC-EXOs treatment activated the Wnt/β-catenin signaling pathway in HTR8/SVneo. Co-treatment by dickkopf-1 (DKK-1) significantly suppressed the activation of Wnt/β-catenin signaling pathway in HTR8/SVneo, and inhibited the proliferation, migration, invasion and EMT (N-cadherin and E-cadherin) of HTR8/SVneo by about 60%, 22%, 42%, 25%, 55% and 21%. These findings indicated that 1-NP exposure could induce the secretion of HDSC-EXOs from HDSCs, which in turn activate the Wnt/β-catenin signaling pathway and enhance the proliferation, migration, invasion and EMT of HTR8/SVneo.
1- 硝基芘（1-NP）是一种广泛存在于内燃机废气颗粒中的代表性硝基多环芳烃污染物，具有致癌性和致突变性。先前的研究表明，1-NP 具有生殖毒性，但具体机制尚不清楚。在这项研究中，用 1-NP 处理人蜕膜基质细胞（HDSC），从 HDSC 的条件培养基中提取外泌体，然后用其处理人绒毛滋养层细胞（HTR8/SVneo）24 小时。结果表明，人蜕膜基质细胞来源的外泌体（HDSC-EXOs）可使 HTR8/SVneo 的增殖、迁移、侵袭和上皮-间充质转化（EMT；波形蛋白和 N-钙黏蛋白）分别增加约 64%、17%、23%、81%和 13%。模拟了妊娠期间母体蜕膜基质细胞调节胚胎滋养层细胞生物学行为的过程。进一步的研究表明，HDSC-EXOs 处理激活了 HTR8/SVneo 中的 Wnt/β-catenin 信号通路。DKK-1 共处理显著抑制了 HTR8/SVneo 中 Wnt/β-catenin 信号通路的激活，并使 HTR8/SVneo 的增殖、迁移、侵袭和 EMT（N-钙黏蛋白和 E-钙黏蛋白）分别减少约 60%、22%、42%、25%、55%和 21%。这些发现表明，1-NP 暴露可诱导 HDSC 从 HDSC 中分泌 HDSC-EXOs，进而激活 Wnt/β-catenin 信号通路，增强 HTR8/SVneo 的增殖、迁移、侵袭和 EMT。
