Division of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China; University of Chinese Academy of Sciences, Beijing, China.
University of Science and Technology of China, Hefei 230026, China; Suzhou Institute for Advanced Research, University of Science and Technology of China, Suzhou, China.
Ecotoxicol Environ Saf. 2024 Oct 15;285:117051. doi: 10.1016/j.ecoenv.2024.117051. Epub 2024 Sep 16.
Maternal exposure to nanoparticles during gestation poses potential risks to fetal development. The placenta, serving as a vital interface for maternal-fetal interaction, plays a pivotal role in shielding the fetus from direct nanoparticle exposure. However, the impact of nanoparticles on placental function is still poorly understood, primarily due to the absence of proper human placental models. In this study, we established a placenta-on-a-chip model capable of recapitulating nanoparticle exposure to assess potential nanotoxicity. The model was assembled by coculturing human trophoblast stem cells (hTSCs) and endothelial cells within a dynamic microsystem. hTSCs exhibited progressive differentiation into syncytiotrophoblasts under continuous fluid flow, forming a bilayered trophoblastic epithelium that mimicking both structural and functional aspects of human placental villi. Copper oxide nanoparticles (CuO NPs) were introduced into the trophoblastic side to simulate maternal blood exposure. Our findings revealed that CuO NPs hindered hTSCs differentiation, leading to diminished hormone secretion and impaired glucose transport. Subsequent analysis indicated that CuO NPs disrupted the autophagic flux in trophoblasts and induced apoptosis. Furthermore, the placenta-on-a-chip model exhibited inflammatory responses to CuO NP exposure, including maternal macrophage activation, inflammatory cytokine secretion, and endothelial barrier disruption. Dysfunction of the placental barrier and the ensuing inflammatory cascades may contribute to aberrant fetal development. Overall, our placenta-on-a-chip model offers a promising platform for assessing nanoparticle exposure-related risks and conducting toxicology studies.
母体在妊娠期间暴露于纳米颗粒可能会对胎儿发育造成潜在风险。胎盘作为母体-胎儿相互作用的重要界面，在保护胎儿免受直接纳米颗粒暴露方面起着关键作用。然而，由于缺乏适当的人类胎盘模型，纳米颗粒对胎盘功能的影响仍知之甚少。在这项研究中，我们建立了一种胎盘芯片模型，能够模拟纳米颗粒暴露，以评估潜在的纳米毒性。该模型通过在动态微系统中共同培养人滋养层干细胞（hTSC）和内皮细胞来组装。hTSC 在连续的流体流动下逐渐分化为合胞滋养层细胞，形成双层滋养层上皮，模拟了人类胎盘绒毛的结构和功能方面。将氧化铜纳米颗粒（CuO NPs）引入滋养层侧以模拟母体血液暴露。我们的研究结果表明，CuO NPs 阻碍了 hTSC 的分化，导致激素分泌减少和葡萄糖转运受损。随后的分析表明，CuO NPs 破坏了滋养细胞中的自噬流并诱导了细胞凋亡。此外，胎盘芯片模型对 CuO NP 暴露表现出炎症反应，包括母体巨噬细胞激活、炎症细胞因子分泌和内皮屏障破坏。胎盘屏障功能障碍和随之而来的炎症级联反应可能导致胎儿发育异常。总体而言，我们的胎盘芯片模型为评估纳米颗粒暴露相关风险和进行毒理学研究提供了一个有前途的平台。
