Preterm labour: clinical and biochemical mechanisms
The mechanism for human parturition remains elusive and when deliveries occur preterm (<37 weeks gestation) there is increased neonatal mortality. Preterm birth is the most important cause of adverse infant outcome (1). Clinical risk factors for preterm labour include previous preterm delivery, infection (chorioamnionitis), antepartum bleeding, premature rupture of the membranes and smoking (2). This project focuses on better understanding of uterine contractility, comparing physiological pathways e.g. activation of oxytocin or epidermal growth factor receptors (3), and inflammatory pathways mediated by cytokines (4). We will study protein phosphorylation in myometrial tissue during episodes of contraction and relaxation (5). Uterine tissues will be obtained with informed consent from women delivering at St Michael’s Hospital, Bristol. Laboratory work will be based at the Dorothy Hodgkin Building. The project will identify the intracellular signalling pathways involved in different clinical subgroups of idiopathic and complicated preterm labour (6).
Translational focus: There is a need to develop uterine-specific drugs that relax myometrial smooth muscle selectively, so that preterm labour can be inhibited with minimal side effects for the mother or the baby. The results will establish a scientific rationale for the clinical use of available prostaglandin and oxytocin receptor agonists and antagonists and will provide new uterine targets for pharmacological intervention. The results will also benefit studies on induction of labour. This project will be ideal for a PhD student interested in clinical and laboratory aspects of human parturition and preterm labour.
Requires full time PhD tuition fees for three to four years
Bench fee (annual): £15,000
When applying please select ’Medicine PhD’ within the Faculty of Health Sciences.
1. Saigal S, Doyle LW. An overview of mortality and sequelae of preterm birth from infancy to adulthood. Lancet. 2008;371(9608):261-9.
2. Ion RC, Wills AK, Bernal AL. Environmental Tobacco Smoke Exposure in Pregnancy is Associated With Earlier Delivery and Reduced Birth Weight. Reprod Sci. 2015;22(12):1603-11.
3. Pont JN, McArdle CA, Lopez Bernal A. Oxytocin-stimulated NFAT transcriptional activation in human myometrial cells. Mol Endocrinol. 2012;26(10):1743-56.
4. Phillips RJ, Fortier MA, Lopez Bernal A. Prostaglandin pathway gene expression in human placenta, amnion and choriodecidua is differentially affected by preterm and term labour and by uterine inflammation. BMC Pregnancy Childbirth. 2014;14(1):241.
5. Hudson CA, Heesom KJ, Lopez Bernal A. Phasic contractions of isolated human myometrium are associated with Rho-kinase (ROCK)-dependent phosphorylation of myosin phosphatase-targeting subunit (MYPT1). Mol Hum Reprod. 2012;18(5):265-79.
6. Wouters E, Hudson CA, McArdle CA, López Bernal A. Central role for protein kinase C in oxytocin and epidermal growth factor stimulated cyclooxygenase 2 expression in human myometrial cells. BMC research notes. 2014;7:357.