Mashayamombe, Chipo (2015) A rat model study of the spatio-temporal effects of progesterone signalling on the transcriptome of uterine tissues during pregnancy and parturition. PhD thesis, University of Warwick.

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Abstract

The steroid hormone progesterone is essential for the maintenance of pregnancy in mammalian species, but its role at term and during labour is not fully understood. While the effects of progesterone be either genomic or non-genomic, this thesis focuses on the genomic effects of progesterone, and its withdrawal, on rat uterine tissues. Using laser Capture Microdissection, homogeneous cell populations from the the outer myometrium, inner myometrium, and decidua basalis were isolated from uterine horns obtained from timed-pregnant Sprague Dawley rats that were randomised to receive either progesterone, mifepristone, or vehicle treatment. These rats had a 22-day gestational period, with natural systemic withdrawal of progesterone occurring on the 19th day of gestation (GD19). RNA sequencing was employed in the examination of the transcriptomes of the uterine layers, as well as gene expression profiling between GD19 and term. Analysis of the spatial expression of mRNA and proteins in the uterine tissues revealed localisation of thyrotropin-releasing hormone mRNA, as well as the Trh protein, to the decidua in late pregnancy. In addition, tenascin-n mRNA and proteins localised to the inner myometrium but not the outer myometrium during late pregnancy. Analysis of the temporal expression of mRNA transcripts showed distinct patterns of expression within each of the analysed tissues. Following the withdrawal of progesterone on GD19, changes first occur in the outer myometrium, followed by the inner myometrium, then the decidua where mRNA expression increases between GD22 before labour and GD22 during labour. In conclusion, this thesis presents a novel approach in which rat uterine tissues were studied separately. Potential tissue-specific markers for the decidua and the inner myometrium in late pregnancy were identified. The increase in gene expression prior to labour in the decidua would suggest a signal for the onset of labour. Furthermore, changes in the myometrial tissues suggest the presence of an in-built mechanism through which the myometrium knows when to prepare for labour.

Item Type:	Thesis or Dissertation (PhD)
Subjects:	Q Science > QP Physiology
Library of Congress Subject Headings (LCSH):	Progesterone, Pregnancy in animals, Rats -- Parturition, Uterus
Official Date:	September 2015
Dates:	Date Event September 2015 Submitted
Institution:	University of Warwick
Theses Department:	Systems Biology Doctoral Training Centre
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Blanks, Andrew M. ; Berg, Hugo van den
Sponsors:	University of Warwick. Systems Biology Doctoral Training Centre ; Biotechnology and Biological Sciences Research Council (Great Britain)
Extent:	xl, 352 leaves : illustrations, charts
Language:	eng

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