BRC-BIO: Trophoblast invasiveness influencing exosome-mediated cell communication

The placenta is a crucial organ that supports in utero human development; yet, it is one of the least understood human organs. Within the placenta, trophoblasts are the main cellular component and play several biological roles, including invasion into the endometrium to anchor the placenta and to facilitate nutrient and waste transport. The biochemical signals that regulate trophoblast function are unclear. The goal of this proposal is to better understand how the tissue microenvironment promotes cell growth and secreted extracellular vesicles within that microenvironment influence trophoblast invasiveness. Besides potentially transforming our current knowledge of factors influencing trophoblast invasion, the anticipated results may inform molecular mechanisms that regulate cellular invasion in other healthy and disease tissues. In addition, the project will build research capacity by expanding experiential research experiences and fostering didactic training at the intersection of cell biology and biomanufacturing. In the placenta, there are two main types of trophoblast cells, villous and extravillous trophoblasts, that have important and distinct functions. Villous trophoblast cells are important for nutrient and waste transport, while extravillous trophoblasts facilitate host integration by invading decidualized endometrium. Both types of trophoblasts secrete extracellular vesicles called exosomes, which are thought to play an important role in cellular communication and regulating cell phenotype. The PI hypothesizes that the trophoblast environment influences invasiveness, and that this consequentially impacts exosome production and composition. To test this hypothesis, two objectives are proposed. The first objective will focus on characterizing how oxygen tension and biochemical factors influence trophoblast invasion of extracellular matrix. The second will focus on characterizing how oxygen tension and biochemical factors alter exosomal payload, which in turn alters trophoblast invasiveness. Trophoblast function within the placenta, including their invasive potential, make them an ideal candidate to study the relationship between invasion and exosome-mediated communication. While the anticipated findings will inform placental function, this research will also further knowledge on cell migration and invasion applicable to several cell types that experience similar biochemical cues. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.