Low oxygen concentration, or hypoxia, is an important physiological regulator of placental function including chemical disposition. Here, we compared the ability of low oxygen tension to alter the expression of solute carriers (SLC) and ABC transporters in two human placental models, namely BeWo cells and term placental explants. We found that exposure to low oxygen concentration differentially regulates transporter expression in BeWo cells, including down-regulation of ENT1, OATP4A1, OCTN2, BCRP, MRP2/3/5, and up-regulation of CNT1, OAT4, OATP2B1, SERT, SOAT, and MRP1. Similar up-regulation of MRP1 and down-regulation of MRP5 and BCRP was observed in explants, whereas uptake transporters were decreased or unchanged. Furthermore, a screening of transcriptional regulators of transporters revealed that hypoxia leads to a decrease in the mRNA levels of AHR, NRF2, and RXRα in both human placental models. These data suggest that transporter expression is differentially regulated by oxygen concentration across experimental human placental models.

中文翻译：

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低氧张力差异调节胎盘溶质载体和ABC转运蛋白的表达

低氧浓度或缺氧是胎盘功能（包括化学处置）的重要生理调节剂。在这里，我们比较了低氧张力在两种人类胎盘模型（即 BeWo 细胞和足月胎盘外植体）中改变溶质载体 (SLC) 和 ABC 转运蛋白表达的能力。我们发现暴露于低氧浓度会差异调节 BeWo 细胞中的转运蛋白表达，包括下调 ENT1、OATP4A1、OCTN2、BCRP、MRP2/3/5，以及上调 CNT1、OAT4、OATP2B1、SERT、SOAT、和 MRP1。在外植体中观察到类似的 MRP1 上调和 MRP5 和 BCRP 下调，而摄取转运蛋白减少或不变。此外，对转运蛋白转录调节因子的筛选显示，缺氧导致两种人胎盘模型中 AHR、NRF2 和 RXRα 的 mRNA 水平降低。这些数据表明，跨实验人类胎盘模型中，转运蛋白的表达受到氧浓度的不同调节。