Reproduction in Domestic Animals - Facultad de Ciencias Veterinarias

16 t h International Congress on Animal Reproduction
Workshop Abstracts 25
Workshop 17 - Equine Endometritis
Moderator: Terttu Katila (Finland)
WS17-1
Uterine response to insemination in mares
Reilas, T
Department of Equine Research, MTT Agrifood Research, Finland
Breeding causes an acute endometrial inflammation characterised by
increased vascular permeability, exudation of fluids and leukocyte
migration into the uterine lumen. In reproductively normal mares, the
first polymorphonuclear neutrophils (PMNs) enter the uterine lumen
within 1 h after artificial insemination (AI), the highest numbers are
found around 8 h and at 48 h there are very few, if any PMNs left.
This protective process elicited predominantly by spermatozoa may
develop into persistent mating-induced endometritis (PMIE) if uterine
drainage mechanisms fail to remove excess spermatozoa, bacteria and
debris. In addition to predisposing factors for endometritis, the
composition and volume of the inseminate influence the kinetics of
endometrial inflammation. Insemination with small volumes of highly
concentrated frozen semen has been shown to provoke a greater
neutrophil response 6 h after AI than insemination with larger
volumes of less concentrated semen or infusion of extender. The
difference between frozen semen and extender is no longer visible at
96 h post-infusion. In studies where the volume has been constant (20
or 40 ml), higher sperm concentrations have resulted in higher
numbers of PMNs 2 h after AI, and lower numbers of PMNs 48 h
after AI. Unlike spermatozoa, seminal plasma has been shown to
suppress PMN chemotaxis in vitro. However, equine seminal plasma
increases the intensity of uterine inflammation in vivo. The increased
early inflammatory response may explain the reduced duration of
inflammation seen in another study when seminal plasma was present
in the inseminate. A strong inflammatory response to frozen semen
deposition has worried practitioners. However, it is not known to what
extent the beginning programs the end. More research is needed to
find out if down-regulation of the early stages of inflammation
benefits fertility. Bacteria propably play an important role in the
pathogenesis of PMIE. Mares, that had histopathological changes in
the endometrium, or were unable to clear intrauterine bacterial
inoculations within 96 h, were shown to have similar PMN numbers
as normal mares 24 or 96 h after AI with frozen semen. Many mares
suffering from PMIE have a delay in uterine clearance because of
diminished myometrial contractility. It is well-known that myometrial
contractions are required for resolution of inflammation. It has been
shown that treatment with oxytocin facilitates clearance of
intrauterine fluid and in doing so, also shortens the duration of
inflammation and improves pregnancy rates.
WS17-2
Equine endometrosis – an own entity or just a result of
chronic endometritis
Ellenberger, C 1 *; Mattos, RC 2 ; Schoon, HA 1
1Faculty of Veterinary Medicine, Institute of Pathology, University of Leipzig,
Germany; 2 REPROLAB, Departamento de Medicina Animal, Brazil
Equine endometrosis is the most important clinical chronic
endometrial disease associated with infertility in mares. It cannot be
discovered by conventional clinical examinations, whereas the
histopathological investigation of an endometrial biopsy specimen has
proven to be of high value. The term endometrosis describes a
periglandular and/or stromal endometrial fibrosis including glandular
alterations within fibrotic foci. The frequency and the degree of
endometrosis increases with the age of the mares, however there is no
correlation to the number of previous foalings.
For a detailed immunohistochemical (oestrogen and progesterone
receptors, endometrial secretory proteins) characterization of equine
endometrosis, 509 endometrial biopsies were selected from routine
submissions. Additionally, 200 biopsies from 20 mares with 5
consecutive experimentally induced bacterial (1 x 10 9 S. equi subsp.
zooepidemicus) endometritis and subsequent treatments with at least a
14-day interval were collected over a 2-year period to investigate the
potential effects of endometritis on the progress of endometrosis. One
day before and 5 days after each experimental infection, an
endometrial biopsy was taken from all mares.
Immunohistochemically, the endometrotic glands showed a cycleasynchronous
staining for oestrogen and progesterone receptors when
compared to non-affected healthy glands. These findings indicate that
affected areas become independent of the uterine control mechanisms
and exhibit own differentiation dynamics. Furthermore, there are
apparent deviations in the secretory protein expression patterns in
fibrotic areas. In 73% of the biopsies taken 5 days post infection of
mares with repeatedly experimentally induced endometritis an
exudative (30.1%), non-purulent (42.5%) or eosinophilic (27.4%)
inflammation was detectable. Half of these mares showed a temporary
metabolic activation of the endometrosis; however the degree of the
endometrosis had not changed over the 2-year period of the
experiment.
The findings indicate that an aberrant secretion of endometrial
proteins may be one disturbing factor in the intrauterine
microenvironment that contributes to the pathogenesis of
endometrosis induced fertility problems. Repeatedly induced
endometritis has no remarkable influence on the progress of
endometrosis. Therefore, endometrosis describes a degenerative
endometrial alteration independent of endometritis. Although
profibrotic effects of endometritis were demonstrated, the initial
reason of this disease still remains unclear.
WS17-3
Development of endometrial fibrosis in the mare
Oddsdottir, C*, Björnsdóttir, S, Riley, SC, Watson, ED
Division of Veterinary Clinical Studies, University of Edinburgh, Iceland
Endometrial fibrosis in the mare is an important cause of infertility.
The condition is characterised by an abnormal deposition of collagen
with advancing age. The fibrosis reduces the efficacy of uterine
defence mechanisms and the uterine capacity for foetal nutrition.
Organ fibrosis has been extensively researched, and found to be a
result of ongoing, altered tissue repair. Normally, the repair
mechanism is a self-limiting process involving collagen deposition
and degradation, resulting in reconstitution of tissue structure. Repair
occurring as a consequence of chronic tissue destruction will go on as
long as there is tissue injury, and eventually results in the
accumulation of excess collagen. This happens due to the deposition
of collagen without final scar resolution, and can be seen in chronic
inflammation of the liver, lung and kidney. Matrix metalloproteinases
(MMPs) are important enzymes capable of collagen remodelling.
Different individuals tend to develop varying degrees of fibrosis
when exposed to a similar stimulus, and certain genes carry a
predisposition to fibrosis. Furthermore, liver fibrosis can be halted
and even reversed to some extent.
Great individual variation is also seen in the severity of endometrial
fibrosis in mares, as well as the age of onset, which could indicate a
genetic predisposition similar to what is seen in other organs. No
treatment or preventative measures are known for the condition and
therefore a better knowledge of the pathogenesis is desirable. As in
other organs, it is likely that tissue injury instigates the deposition of
collagen in the endometrium, possibly due to the altered expression of
MMPs. In a study on uterine secretions and endometrial biopsies
from 49 mares, the relationship between endometrial collagen density
and various factors hypothesised to influence the deposition of
collagen was investigated. The activity of MMPs and their inhibitors
was not shown to correlate with collagen density in the endometrium,
possibly due to the absence of active collagen remodelling at the time
of sampling. A statistically significant positive relationship was
found between collagen density and an increase in inbreeding
coefficient. The results indicate that a genetic factor predisposes
individual mares to developing endometrial fibrosis with more
severity and at an earlier age than others.