Division of Basic Science and Translational Research, Department of Obstetrics & Gynecology, The University of Texas Medical Branch at Galveston, Texas, USA.
Department of Biochemistry and Molecular Biology, University of the Philippines Manila, Manila, Philippines.
Lab Chip. 2024 Mar 12;24(6):1727-1749. doi: 10.1039/d3lc00998j.
The effects of endocrine-disrupting compounds (EDCs) on the placenta, a critical gestational organ for xenobiotic protection, are well reported; however, models to determine the role of EDCs in placental disruption are limited. An advanced 2nd-trimester human placenta organ-on-chip model (2TPLA-OOC) was developed and validated, with six representative cells of the maternal and the fetal interface interconnected with microchannels. Various EDCs (150 ng mL each of bisphenol A, bisphenol S, and polybrominated diphenyl ethers-47 and -99) were gradually propagated across the chip for 72 hours, and their various effects were determined. Cigarette smoke extract (CSE), an environmental risk factor, was used as a positive control. EDCs produced overall oxidative stress in the placental/decidual cells, induced cell-specific endocrine effects, caused limited (<10%) apoptosis/necrosis in trophoblasts and mesenchymal cells, induced localized inflammation but an overall anti-inflammatory shift, did not change immune cell migration from stroma to decidua, and did not affect placental nutrient transport. Overall, (1) the humanized 2TPLA-OOC recreated the placental organ and generated data distinct from the trophoblast and other cells studied in isolation, and (2) at doses associated with adverse pregnancies, EDCs produced limited and localized insults, and the whole organ compensated for the exposure.
内分泌干扰化合物 (EDCs) 对胎盘的影响已有大量报道，胎盘是妊娠期间保护外来物质的关键器官；然而，用于确定 EDC 对胎盘损伤作用的模型却十分有限。本研究开发并验证了一种先进的妊娠中期人类胎盘类器官模型（2TPLA-OOC），该模型包含与微通道相连的母胎界面的六种代表性细胞。将各种 EDC（双酚 A、双酚 S 和多溴二苯醚-47 和 -99 各 150ng/ml）逐渐穿过芯片传播 72 小时，并确定其各种影响。香烟烟雾提取物（CSE）作为环境风险因素被用作阳性对照。EDCs 导致胎盘/蜕膜细胞产生整体氧化应激，诱导细胞特异性内分泌效应，引起滋养层和间充质细胞中有限的（<10%）细胞凋亡/坏死，引起局部炎症但整体抗炎转移，不会改变免疫细胞从基质向蜕膜的迁移，也不会影响胎盘的营养转运。总的来说，（1）该类器官重现了胎盘器官，并产生了与单独研究的滋养层和其他细胞不同的数据；（2）在与不良妊娠相关的剂量下，EDCs 产生了有限且局部的损伤，整个器官对暴露做出了代偿。
