内分泌干扰化合物及其对人类胎盘功能的影响:来自胎盘器官芯片研究的证据
Manuel S Vidal1,2, Lauren S Richardson2, Ananth Kumar Kammala2
1Division of Basic Science and Translational Research, Department of Obstetrics & Gynecology, The University of Texas Medical Branch at Galveston, Texas, USA. ra2menon@utmb.edu.
Lab on a chip
|February 9, 2024
概括
这项研究引入了人类胎盘器官芯片模型,以评估内分泌干扰化合物 (EDC). 该模型显示EDCs会引起局部炎症和氧化应激,但胎盘会弥补这些影响.
科学领域:
- 生殖毒理学 生殖毒理学
- 发育生物学是发展生物学.
- 器官在芯片上的技术
背景情况:
- 内分泌干扰化合物 (EDC) 对胎盘功能构成风险.
- 现有的模型在评估EDC对整个胎盘的影响方面是有限的.
- 胎盘对于保护胎儿免受外来生物的侵害至关重要.
研究的目的:
- 开发和验证第2个三个月的人类胎盘器官芯片 (2TPLA-OOC) 模型.
- 调查代表性EDC对胎盘细胞和功能的影响.
- 为了确定胎盘对EDC暴露的补偿机制.
主要方法:
- 开发了第二个妊娠期人类胎盘器官芯片模型,其中包含相互连接的母体和胎儿细胞.
- 将模型暴露在双A,双S和多二乙烯 (PBDE) 中72小时.
- 评估氧化应激,细胞活力,炎症,免疫细胞迁移和营养物质运输.
主要成果:
- EDCs在胎盘细胞中诱导了氧化应激和细胞特异性内分泌作用.
- 在 trofhoblasts 和 mesenchymal 细胞中观察到有限的亡 (<10%).
- 发生局部炎症,但整体反应是抗炎,对免疫细胞迁移或营养物质运输没有显著影响.
- 与孤立细胞研究相比,2TPLA-OOC模型提供了不同的数据.
结论:
- 开发的2TPLA-OOC模型有效地复制了人类胎盘器官的功能.
- 在与不良妊娠结果相关的剂量下,EDCs引起了有限的,局部的胎盘侮辱.
- 整个胎盘器官表现出能够弥补EDC暴露的能力,减轻广泛的损伤.
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