Monday, May 6, 2024
5/6/2024
ABSTRACT Ninety percent of pregnant U.S. women have simultaneously over 50 different chemicals in their bodies. With over 70,000 chemicals registered with the U.S. Environmental Protection Agency and with many of which not yet evaluated for reproductive toxicity, understanding the effects of chemical exposure on placental function is much warranted. This is significant as many of these chemicals have the potential to alter placental function and the health of the placenta is critical to a healthy pregnancy as well as fetal and maternal well-being. However, studying the effects of chemical exposure on human placental function in vivo is filled with challenges, including ethical concerns, inadequacy of animal models to recapitulate human trophoblast cell invasion, and difficulty of working with limited primary cells that cannot be passaged many times. To advance the field of placental toxicology, suitable in vitro human models capable of mimicking in vivo conditions and enabling dynamic drug delivery in higher-throughput screening formats are urgently needed. Key limitations of available models include low throughput and chemical hepatic biotransformation that occurs in vivo. In this proposal, we plan to develop a high throughput system to test placental cell invasion using a 3D placental microtissue coupled with hepatic liver biotransformation. This first-of-its-kind hepatic-placenta organ-tandem on a chip will simulate the liver metabolism that chemicals undergo in vivo prior to reaching the placental bed. This state-of-the-art in vitro platform will be the first step towards incorporating organism-level organization into reproductive risk assessment using a non-animal-based approach. We anticipate that this new platform will be a key tool to be incorporated in the development of adverse outcome pathways for future placental risk assessment.
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