Expression and function of GPCRs in the pregnant uterus

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BACKGROUND: During pregnancy, the uterus undergoes profound changes both physically as it expands to house the growing baby, and biochemically as many hormonal signals help keep the uterus in a quiescent (relaxed) state until delivery. One group of, hormone like, chemical mediators thought to be important during pregnancy and labour, are the prostaglandins. Since prostaglandin levels rise though pregnancy, especially toward term, these mediators are widely implicated in the stimulation of uterine contractions and the remodeling events necessary for delivery. However, it is not clear whether prostaglandins trigger labour or if the observed increased is simply a consequence of labour being initiated by other factors. Labour is complex and likely to involve numerous factors. Research in my laboratory, focusses on the role of the prostaglandins, and how these may act via interaction with their receptors to promote quiescence during pregnancy and regulate contractions in the pregnant uterus. As the myometrial smooth muscle cells are the contractile component of the uterus, we will use these as a model to study the interactions and pathways of the prostaglandins and their receptors.****GOALS: The goals of the research are (i) to gain a better understanding of the mechanisms that control parturition (labour and delivery), (ii) to identify the factors that are important for maintaining the balance between uterine quiescence during pregnancy and as labour starts, the shift towards contractions, and (iii) build research capacity with the training of highly qualified personnel (HQP).****SIGNIFICANCE AND OUTCOMES: In terms of the research questions, each independent project will identify and characterize key signaling pathways involved in the transition from uterine quiescence during pregnancy to uterine contraction at parturition. Defining the function of the distinct prostaglandin and receptor pathways within the pregnant uterus will not only give insight into the mechanisms of labour, but will also allow insight and additional applications for other smooth muscle organ systems. In terms of HQP, trainees will develop key research skills and be supported to present and publish their work giving a strong platform to become highly successful in the future careers. Using the critical thinking and technical skills in core molecular and pharmacological research methods acquired in this training environment, the HQP will be equipped to continue scientific leadership in Canada towards generating knowledge on the biology of pregnancy and labour.*****