Progesterone action in the myometrium and decidua in preterm birth.

Progesterone is central to many reproductive processes and is critical in regulating the menstrual cycle and maintaining pregnancy. We discuss here similarities in the molecular mechanisms that regulate the process of decidualisation in endometrial stromal cells and uterine quiescence in myometrial smooth muscle cells. We discuss recent evidence that the decidua may be an important mediator of progesterone actions in the onset of labor in mammalian species lacking progesterone withdrawal. These observations have relevance to recent clinical observations of the effect of progesterone administration in the prevention of preterm labor. We suggest that further research is required to understand the role of progesterone in maintaining the decidua in late pregnancy and particular focus should be given to the mechanisms that increase prostaglandin production in the uterus at term.

Towards a computational reconstruction of the electrodynamics of premature and full term human labour.

We apply virtual tissue engineering to the full term human uterus with a view to reconstruction of the spatiotemporal patterns of electrical activity of the myometrium that control mechanical activity via intracellular calcium. The three-dimensional geometry of the gravid uterus has been reconstructed from segmented in vivo magnetic resonance imaging as well as ex vivo diffusion tensor magnetic resonance imaging to resolve fine scale tissue architecture. A late-pregnancy uterine smooth muscle cell model is constructed and bursting analysed using continuation algorithms. These cell models are incorporated into partial differential equation models for tissue synchronisation and propagation. The ultimate objective is to develop a quantitative and predictive understanding of the mechanisms that initiate and regulate labour.

Diurnal variation is lost in preterm deliveries before 28 weeks of gestation.

Preterm delivery is the primary cause of neonatal mortality and morbidity worldwide. Labour at term occurs as a culmination of maturational events in both the fetus and maternal uterus. This process exhibits diurnal variation, with the onset of labour being more common at night. We have confirmed that this diurnal variation is present in gestations between 28 and 36 weeks, but is absent below 28 weeks. We hypothesise that this is because before 28 weeks of gestation, the onset of labour may result from a pathological rather than a physiological process. This may have important implications regarding any pharmacological approach to the prevention and/or treatment of very early preterm labour.