A bioengineered model of human placental exposure to environmental metals during pregnancy

Exposure of pregnant women to toxic metals is an environmental health issue associated with pregnancy complications. Advancing our biological understanding of this problem and mitigating its adverse effects have been challenged by the ethical constraints of human participant research during pregnancy. Here we present a microphysiological system to experimentally simulate and investigate human placental exposure to environmental metals in maternal circulation. An in vitro analogue of the maternal-fetal interface and its dynamic tissue-specific environment are constructed using primary human placental cells grown in a microfluidic device. Using cadmium as a representative toxicant, we show how this system can be used to model the human placental barrier subjected to the flow of cadmium-containing maternal blood and its adverse biological responses and impaired tissue function. Through mechanistic investigation of maternal-to-fetal cadmium transport in this model, we reveal that efflux membrane transporters expressed by trophoblasts may play a protective role against cadmium-induced toxicity. Finally, we demonstrate the potential use of the microphysiological system for discovering metabolic biomarkers for detection and monitoring of cadmium-induced placental dysfunction.