Exposures to environmental hazardous substances, including those in the event of natural and anthropogenic disasters, are known to negatively impact pregnancy, leading to adverse outcomes such as preterm birth (PTB). However, establishing a clear link between exposure and pregnancy risk is challenging, due to lack of a mechanistic knowledge by which toxicants activate pathways causing PTB in maternal-fetal tissues. Unfortunately, current in vitro and in vivo toxicity testing models are either not sufficient in assessing the hazards of tested substances on pregnancy outcomes, do not represent the human in utero structure and functions accurately, or are too costly and low throughput. In addition, assessment of the hazards imposed by exposures to complex environmental samples that may contain a mixture of hazardous chemicals, often observed after disasters, is even more challenging. Here, we propose to develop a feto-maternal (F-M) interface tissue chip-based testing strategy for assessing the human health hazard of environmental substances on PTB. We will also develop and utilize a tissue chip model with higher throughput so that potential hazards of time-sensitive environmental samples, such as from disasters, can be rapidly assessed. Project 3 responds to Superfund Mandates #1: advanced techniques for the detection, assessment, and evaluation of the effect of hazardous substances; and #2: methods to assess the risks to health from hazardous substances.
Exposures to environmental hazardous substances, including those that may be released in the event of natural and anthropogenic disasters, are known to impact pregnancy, leading to adverse pregnancy outcomes like preterm birth. Here, we propose to address our central hypothesis that a tissue chip model mimicking the complex multi-cellular feto-maternal interface can be used to evaluate the mechanistic pathophysiologic pathways related to preterm birth that may be perturbed by complex mixtures of environmental hazardous substances. We will also develop and utilize a higher throughput tissue chip model that can rapidly assess the potential hazard of environmental samples that may lead to preterm birth
- Develop a mechanistic model of PTB in response to environmental toxicants using a Fetal Membrane Tissue Chip Model (F-M Interface1).
- Develop a mechanistic model of PTB in response to environmental toxicants using a Placenta Tissue Chip Model (F-M Interface 2).
- Disaster Research Response (DR2) – Rapidly assess the potential hazard of environmental samples on F-M homeostatis that can lead to PTB using a higher-throughput tissue chip model.