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Title: Prediction of inappropriate myometrial function
Author: Lacey, Lauren
ISNI:       0000 0004 6423 5597
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 2016
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Preterm birth is a major clinical problem, worldwide 15000000 babies are born prematurely each year. Inappropriate myometrial function is a major cause of preterm labour. Preterm labour is the result of multiple pathological processes involving several underlying mechanisms. In all cases, a quiescent uterus in pregnancy changes to one that can produce coordinated, forceful contractions, following an increase in uterine conductivity and contractility, and cervical remodelling to facilitate cervical dilatation. Currently there are several biochemical and clinical tests available to assist in the prediction of preterm birth. Many of these have a very high negative predictive value but their positive predictive value remains low. One in five women in the UK requires induction of labour. The outcomes of this process are again difficult to predict. Both of these areas of obstetrics would benefit from improvements in prediction of clinical outcomes. Previously, phospholipase C like 1 (PLCL1) was identified as a novel intracellular protein found to be significantly downregulated in both the myometrium with the onset of spontaneous labour using sequencing techniques (Chan et al., 2014). It acts as an IP3 chelator, uncoupling phospholipase C from myometrial contractions, maintaining myometrial quiescence and therefore regulating a common pathway to inflammatory, oxytocin or prostaglandin mediated labour. We aimed to develop a clinical test utilising PLCL1 as a quiescence or susceptibility marker to other stimuli to premature labour and to determine if this marker could determine sensitivity to prostaglandins and syntocinon during the induction of labour process. During a prospective observational cohort study, patients were recruited from a preterm prevention clinic throughout mid-pregnancy, and from the antenatal ward when attending for induction of labour at term. Cervical cytobrush samples were taken to obtain cervical epithelial cells. A novel assay was developed to quantify PLCL1 from these samples. There have been various challenges in the process, including the small and varying number of cells obtained, problems with interference from cervical mucus with protein quantification and difficulty adequately lysing our cells to release the protein. We have demonstrated the presence of PLCL1 in cervical cytobrush samples using immunocytochemistry, SDS-PAGE, and western blotting and ELISAs. We have developed a method to isolate our cervical cells from the cervical mucus, lyse these cells and quantify PLCL1 using an ELISA. Our findings demonstrate that PLCL1 is a promising novel protein which could be utilised in the prediction of preterm birth and outcomes of induction of labour. As a susceptibility marker, PLCL1 could be used in conjunction with other markers.
Supervisor: Not available Sponsor: Warwick Medical School
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: RG Gynecology and obstetrics