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|Title: ||Development of endometrial fibrosis in the mare: factors involved in tissue remodelling and collagen deposition|
|Authors: ||Oddsdóttir, Charlotta|
|Supervisor(s): ||Watson, Elaine D.|
Riley, Simon C.
|Issue Date: ||2008|
|Publisher: ||The University of Edinburgh|
|Abstract: ||Age-related degeneration of the equine endometrium is an established and important
cause of fertility problems in thoroughbred mares, causing great loss to the industry.
As a part of the age-related endometrial degeneration complex, an excessive
deposition of collagen leading to endometrial fibrosis is particularly important due to
the limitations it causes to uterine function. The consequences include reduced
efficacy of uterine defence mechanisms and a decrease in the uterine capacity for
Extensive research into the process of fibrosis in other organs has shown that this
condition results from the malfunction of physiological tissue repair mechanisms.
These mechanisms revolve around tissue fibroblasts that due to continuous
stimulation secrete excessive amounts of collagen and inhibit the activation of factors
essential to the normal collagen degradation occurring in scar resolution. Among
these factors are the MMPs, an enzyme family with the ability to degrade
extracellular matrix components such as collagen during the normal repair
mechanisms following tissue injury. The malfunction in the regulation of these
enzymes is important in the development of fibrosis in the liver and other organs.
In this study it was demonstrated that MMPs are involved in the acute uterine
inflammatory response and that they were secreted by infiltrating inflammatory cells.
The cellular mechanisms observed during endometritis in normal mares were
comparable to the normal repair mechanisms known to be altered in the fibrosis of
other organs. These enzymes were present in equine foetal fluids, and their
regulation may be important in the process of abortion and stillbirth. It was
demonstrated that inbreeding may be correlated with increased deposition of
endometrial collagen in a study population of the Icelandic horse breed even though
this breed appears to exhibit less severe endometrial degeneration than what is
known in lighter breeds. It is likely that genetic predisposition leads to the disruption
of normally self-limiting inflammatory and repair mechanisms in the endometrium,
resulting in constant activation of collagen synthesis by local and infiltrating cells.
This thesis has shown that tissue repair mechanisms involving MMPs are likely to be
involved in endometrial fibrosis in the mare. An inherent alteration in these
mechanisms may play a role in the pathogenesis of this condition, and might arise
due to genetic predisposition. Further understanding of the pathways leading to
excess collagen amounts in the endometrium may produce preventative measures,
and even therapeutic targets.|
|Sponsor(s): ||Division of Veterinary Clinical Science scholarship|
RANNÍS (The Icelandic Research Fund for Graduate Students)
|Appears in Collections:||Royal (Dick) School of Veterinary Studies thesis and dissertation collection|
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