skip to main content
Guest
My Research
My Account
Sign out
Sign in
This feature requires javascript
Library Search
Find Databases
Browse Search
E-Journals A-Z
E-Books A-Z
Citation Linker
Help
Language:
English
Vietnamese
This feature required javascript
This feature requires javascript
Primo Search
All Library Resources
All
Course Materials
Course Materials
Search For:
Clear Search Box
Search in:
All Library Resources
Or hit Enter to replace search target
Or select another collection:
Search in:
All Library Resources
Search in:
Print Resources
Search in:
Digital Resources
Search in:
Online E-Resources
Advanced Search
Browse Search
This feature requires javascript
Search Limited to:
Search Limited to:
Resource type
criteria input
All items
Books
Articles
Images
Audio Visual
Maps
Graduate theses
Show Results with:
criteria input
that contain my query words
with my exact phrase
starts with
Show Results with:
Search type Index
criteria input
anywhere in the record
in the title
as author/creator
in subject
Full Text
ISBN
ISSN
TOC
Keyword
Field
Show Results with:
in the title
Show Results with:
anywhere in the record
in the title
as author/creator
in subject
Full Text
ISBN
ISSN
TOC
Keyword
Field
This feature requires javascript
Programming of cardiovascular disease: an exploration of epigenetic mechanisms
Digital Resources/Online E-Resources
Citations
Cited by
View Online
Details
Recommendations
Reviews
Times Cited
External Links
This feature requires javascript
Actions
Add to My Research
Remove from My Research
E-mail
Print
Permalink
Citation
EasyBib
EndNote
RefWorks
Delicious
Export RIS
Export BibTeX
This feature requires javascript
Title:
Programming of cardiovascular disease: an exploration of epigenetic mechanisms
Author:
Rose, Catherine Margaret
Subjects:
cardiovascular disease
;
epigenetics
;
fetal programming
;
sperm
Description:
Fetal exposure to excess glucocorticoid is associated with low birth weight and increased cardiovascular disease risk in first generation offspring. Such phenotypes can be produced experimentally through the administration of the synthetic glucocorticoid dexamethasone (Dex) to pregnant rats during the last week of gestation. These ‘programmed effects’ can be transmitted to a second generation through both maternal and paternal lines. The overall hypothesis for this thesis was that the transmission of programmed effects through the male line may result from alterations in fetal germ cells, which form sperm in adulthood. Epigenetic reprogramming of germ cells is characterised by the genome-wide erasure and subsequent re-establishment of 5-methylcytosine (5mC), however this process has not previously been described for the rat. Furthermore, the involvement of more recently identified cytosine modifications; 5-hydroxymethylcytosine (5hmC), 5- formylcytosine (5fC) and 5-carboxylcytosine (5caC), has not been characterised during germ cell ontogeny. Using immunofluorescence to study DNA modifications during late gestation I identified that 5hmC, 5fC and 5caC were present between e14.5 and e16.5 but absent thereafter. In contrast, 5mC was absent during this time but remethylation was noted from e19.5 onwards. Prenatal Dex exposure was associated with the presence of significantly more 5mC-positive germ cells at e19.5 relative to controls. This difference did not persist at e20.5 suggesting that Dex exposure promotes premature global remethylation. The mechanisms for this are unclear since there were no differences between groups in the localisation of the DNA methyltransferases DNMT3a and 3b, or in markers of normal testis maturation. To enable the study of gene-specific changes in DNA methylation in the germline a colony of Germ Cell Specific-Enhanced Green Fluorescent Protein (GCS-EGFP) rats was established and characterised. GCS-EGFP rats had a transgenerational decrease in pup weight with Dex exposure, as in Wistar rats. The expression of both established and novel candidate genes was compared between strains. Multiple genes across different pathways had altered expression, with some affected in both Wistar and GCS-EGFP rats, whilst other differences were strain-specific. Enhanced Reduced Representation Bisulfite Sequencing was performed on liver and fetal germ cells from males exposed to Dex in utero to explore effects on DNA methylation. These studies confirm that epigenetic reprogramming occurs in the rat and that this process may be susceptible to modification by prenatal Dex exposure. GCS-EGFP rats also exhibited a Dex programming phenotype, with decreased pup weight and altered liver gene expression. The use of this unique strain of rats will permit dissection of the mechanisms for the transmission of programmed phenotypes across generations.
Publisher:
The University of Edinburgh
Creation Date:
2015
Language:
English
Source:
University of Edinburgh dspace
This feature requires javascript
This feature requires javascript
Back to results list
This feature requires javascript
This feature requires javascript
Searching Remote Databases, Please Wait
Searching for
in
scope:(TDTS),scope:(SFX),scope:(TDT),scope:(SEN),primo_central_multiple_fe
Show me what you have so far
This feature requires javascript
This feature requires javascript