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Title: Factors affecting natural antimicrobial expression in the human female reproductive tract
Author: Dalgetty, Donna Marie
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2008
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Mimics of infection such as lipopolysaccharide, lipoteichoic acid and cytokines were demonstrated to alter the mRNA expression of natural antimicrobial molecules in the endometrial epithelial cell line Hec-1A (human endometrial carcinoma). The expression of natural antimicrobials was both phasic and time dependent. Changes in expression levels were also observed in primary endometrial stromal cell lines. The interaction between the epithelial and stromal cells concurrently with the addition of mediators of inflammation also yielded a change in mRNA expression. The presence of stromal derived media and mimics of infection caused an increase and earlier expression of molecules such as elafin in the Hec-1A cell line. However, with the addition of progesterone treated stromal derived media, a downregulation of elafin was observed. Further investigation suggested a role for progesterone either directly upon the epithelial cells, which proved to have high levels of genomic progesterone receptors or via stromal mediated factor(s). In the presence of progesterone endometrial stromal cells up-regulate the level of TGFβ-1 and this has been shown to decrease the epithelial expression of both MMP-7 and elafin. Antimicrobials are differentially expressed within the human Fallopian tube collected during different stages of the ovarian cycle and this appeared to be governed by the circulating levels of the exogenous sex steroids. Many of these molecules were also observed to be increased in Fallopian tube in response to the presence of an ectopic pregnancy. The uterine decidua from an ectopic gestation was also demonstrated to show differential expression to that observed in the deciduas where early pregnancy (ongoing or failed) was intrauterine. Further research may offer preventive, diagnostic and treatment opportunities in adverse pregnancy outcomes.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available