Grant: Discovery Grants Program - Individual

) The uterus is a female organ that houses the developing fetus during pregnancy. This organ contains a smooth muscle component named the myometrium and during pregnancy the myometrium goes through a program of differentiation. The rat has been well utilized as an animal model to study this myometrial programming. During rat pregnancy the myometrium is characterized by a Proliferative Phase, a Synthetic Phase, a Contractile Phase, a Labour Phase, and lastly, a post-partum Involution Phase. Each one of these phases of differentiation is characterized by changes in the muscle cells at the molecular and cellular level. Overall, the consequence of this whole process is the production of a tissue that can generate precisely coordinated and powerful contractions (labour) to ensure the timely delivery of a term fetus whose organ systems are sufficiently mature for survival outside the uterus. ) Small stress or heat shock proteins (Hsp) have important housekeeping roles in cells while heat shock factors (HSF) are master regulators of gene transcription, including that of classical and non-classical heat shock genes. This research program will determine the presence (expression) and regulation of HSF-1, -2, HspB8 and associated proteins in myometrial cells during pregnancy. Moreover, we will determine if any of these molecules have key roles to play in specific phases of myometrial programming. The research will utilize molecular and cell biological tools and procedures, as well as rat experimental models to achieve the research objectives. In total, this research program will create a greater fundamental understanding of the expression, regulation and role of HSF1/2, HspB8 and associated chaperone machinery in myometrial programming during pregnancy.