Grant: Project Grant

Preterm labour and delivery before 37 weeks of pregnancy is a serious health problem. Babies, born too soon, may face difficulties breathing, suffer with brain injury or long-term disability. Unfortunately, current clinical treatments to stop preterm labour do not work. To improve this, we must gain a better understanding of the labour process. The key to addressing the problem may be the uterus itself. Questions to ask include; how does the uterus expand throughout pregnancy to house the growing baby yet still stay inactive (quiescent), how does this change at term when contractions begin and the baby is delivered, and, what factors affect this balance that shift the uterus to the onset of preterm labour. Specialised cells within the uterus, called myometrial smooth muscle cells, provide the contractile machinery of the uterus. Located on these cells are receptors, regulated by biochemical and hormonal signals to cause either contractions or to enhance relaxation. The response of each myometrial cell is dependent on the type of signal and the specific receptor at which it acts. The aim of this project is to better understand the role of receptors present in the pregnant uterus, those important for maintaining quiescence in pregnancy, and those that stimulate contractions during labour. To this end we recently identified receptors, from the G-protein coupled receptor (GPCR) family, present and previously unidentified in the pregnant uterus, and some of which show differential localisation and regulation with pregnancy and labour. We will use myometrial tissue and myometrial cell culture models to investigate GPCR function within the pregnant uterus, and how this may be regulated with labour, term and preterm. Knowledge generated will be clinically relevant in the management of labour, especially pre-term labour, where pharmacological strategies aimed to promote or maintain quiescence may be beneficial in delaying labour onset.