PROJECT SUMMARY Matrix Metalloproteinases 2 and Metalloproteinase 9 (MMP2/9) play active roles in a variety of cellular responses, including the regulation of uterine contraction. The underlying molecular mechanisms driving these effects are currently unknown. The overall objective of the parent proposal is to understand the mechanisms by which MMP9 promotes uterine contraction and to determine if specific inhibition of MMP9 promotes uterine quiescence. The central hypothesis is that elevation of MMP9 to levels seen in preterm patients is sufficient to increase the contractile response in human uterine tissue and drive preterm parturition. The parent project includes experiments will be performed to determine if MMP9 inhibition can delay parturition in preterm mouse models. This supplemental project will enhance the parent proposal by identifying genes and proteins whose uterine expression is altered when MMP activity is systemically blocked. These data are expected to be significant because these they will identify potential mechanistic links to explain how MMP2/9 modulate uterine contractions. These data will provide a foundation for future experiments to determine if MMP2/9 substrates can serve as druggable targets to promote uterine quiescence and reduce the number preterm births.