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Title: The role of the fibroblast in the human pregnant cervix
Author: Cowan, Shona
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2006
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The hypothesis that there is a phenotypic variation in cervical stromal cells akin to decasualisation is investigated in this thesis. This work uses human cervical explants and cervical stromal cell culture, from both pregnant and non-pregnant women, to elucidate a phenotypic alteration in the cervical stromal cell under the influence of progesterone. This altered cervical fibroblast phenotype has extensive implications in the study of the mechanism of pregnancy associated cervical remodelling. Cervical ripening in the last few weeks of pregnancy has also been likened to an inflammatory reaction with invasion of leukocytes, activation proinflammatory cytokines and of connective tissue degrading matrix metalloproteinases.  Prior studies have observed upregulation of collagen and proteoglycan degrading MMPs in the labour cervix. However, if leukocyte extravasation is a key component to cervical remodelling at term, then MMP-2, whose main substrate is collagen type IV i.e. basement membrane, would provide a mechanism to facilitate this. ProMMP-2 requires activation by MMP-14. This work investigates the expression of MMP-14 in cervical explants and cultured stromal cells, and demonstrates an upregulated MMP-14 expression response to a prostaglandin E2 challenge, an effective cervical ripening agent. MMP-14 expression is also measured in a monocyte cell line, activated and treated with prostaglandin E2 in an attempt to elucidate the origin of this upregulation. In addition a small study of potential direct clinical benefit is performed to assess the capability of a needle-free injection device to administer a solution to the human uterine cervix. The purpose of this is to prove the principal of a potential new drug delivery method for cervical ripening agents. The clinical implications of this work will be for induction of labour, termination of pregnancy and ectopic pregnancy as well as providing potential insights into the pathophysiology of preterm delivery where the primary aetiology is disruption of cervical integrity.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available