Reproduction in Domestic Animals - Facultad de Ciencias Veterinarias

16 t h International Congress on Animal Reproduction
Workshop Abstracts 5
WORKSHOP ABSTRACTS
Workshop 01 - Pathophysiology and Immunology of
Postpartum Uterine Disease in Cattle
Moderator: Martin Sheldon (UK)
WS01-1
The pathogens and the cause of uterine disease
Földi, J 1,2 ; Pécsi, A 3 ; Szabó, J 4 ; Kulcsár, M 2 ; Egyed, L 5 ; Huszenicza, G 2 *
1Intervet International B.V., Boxmeer, Holland; 2 Faculty of Veterinary Science,
Szt. István University, Budapest, Hungary; 3 Faculty of Agricultural Science,
University of Debrecen, Hungary; 4 Faculty of Medical Science, University of
Debrecen, Hungary; 5 Veterinary Medical Research Institute, Budapest,
Hungary
A wide variety of bacteria are present in the uterus of all cows at the
first 10-14 postpartum (pp) days, regardless of disease signs. Mostly
Streptococcus spp., Staphylococcus spp. and Bacillus spp. were
isolated from the uterus of cows with physiological involution, while
Arcanobacterium pyogenes (A. pyo), Escherichia coli (E. coli) and
different Gram negative (GN) anaerobic bacteria namely
Fusobacterium necrophorum, Prevotella spp. and Bacteroides spp.
were predominant in the uterus of clinically diseased animals. Series
of studies confirmed that clinical and reproductive consequences are
associated with these ‘primary uterine pathogen bacteria’. Although
E. coli plays a key role in puerperal metritis (up to 14 days pp) i.e.
systemic signs of the disease are endotoxin mediated, its influence
decreases by the time of involution. Clinical endometritis/pyometra
is mostly the result of a chain of re-infection with A. pyo and GN
anaerobes. A. pyo acts synergistically with F. necrophorum,
Bacteroides spp. and Prevotella spp. Isolation of A. pyogenes at the
late involution period (28-35 days) is associated with dramatically
decreased re-conception rate.
Bovine herpesvirus type 4 (BoHV-4) is a member of Rhadinovirus
genus within the Gammaherpesvirinae subfamily. BoHV-4 is unique
among the BoHVs concerning its wide tropism of species as well as
tissue distribution including reproductive organs. BoHV-4 has been
associated with abortion and (puerperal) metritis since 1973, however,
its endometriotropism and the symbiotic relationship between
endometrial stromal cells and macrophages persistently infected with
the virus has most recently been proven. It supports the concept that
BoHV-4, as a secondary pathogen, decreases the local immune
response and as such, promotes bacterial metritis.
Presence of pathogens in the uterus i.e. (bacterial) contamination does
not always result in inflammation. Even the colonization of the entire
uterine wall i.e. (bacterial) infection as such, does not necessarily
mean a clinical disease; it depends on the immune status of the host.
The course of uterine involution may be considered as a ‘see-saw
balance’: in a physiological situation the self-defence mechanisms are
able to counteract the bacterial and/or viral infection.
On a herd level, the most important risk factors of metritis are:
metabolic disorders i.e. hyperketonaemia and/or ketonuria,
hypocalcaemia; dystocia, retained foetal membranes, manual
intervention at calving (associated with poor hygiene), herd size,
season, parity, high milk production and lack of grazing.
WS01-2
The host and nature of postpartum uterine disease in
dairy cows
Gilbert, RO
Cornell University, Ithaca, NY, USA
Fetal membranes are usually expelled within 6 hours after delivery
and are regarded as retained after 12 or 24 hours. The incidence in
dairy cows is about 5 – 15%. Risk of retention is increased by
abortion, stillbirth, low birthweight, multiple birth, premature
parturition, dystocia, heat stress and hypocalcemia. Deficiency of
antioxidant nutrients such as selenium and vitamin E is also
implicated. Retention of fetal membranes is associated with impaired
prepartum immune function, particularly with reduced activity of
neutrophils. This impairment extends into the postpartum period and
mediates increased susceptibility to subsequent uterine disease and
mastitis.
Puerperal metritis, characterized by malodorous, red-brown uterine
exudate and uterine atony before 14 days postpartum affects up to
40% of dairy cows in some herds. Systemic signs including fever,
depression or malaise are inconsistent. Reduced dry matter intake in
late pregnancy, resulting negative energy balance and impaired
immune function contribute to the pathogenesis of this condition as
well as clinical and subclinical endometritis. Cows with metritis are at
increased risk for subsequent endometritis. Response to treatment is
generally favorable. Most cows with overt uterine disease do not
ovulate early in the postpartum period. Cows ovulating in the face of
continued uterine infection may be predisposed to development of
pyometra – an accumulation of purulent exudate in the uterine lumen
in the presence of a persistent corpus luteum.
Clinical endometritis is best diagnosed and treated after 4 weeks
postpartum when purulent material is demonstrable in the uterus or
vagina by ultrasonography, vaginoscopy, manual inspection, or use of
a specifically designed instrument (Metricheck®) or if the cervix
remains larger than 7.5 cm in diameter. Presence of these signs is
associated with reduced likelihood of subsequent pregnancy.
Pregnancy risk is increased by treatment with intrauterine cephapirin
or systemic prostaglandin F2alpha.
Many cows without overt signs of infection have persistent uterine
inflammation at the beginning of the rebreeding period. This
condition is best diagnosed by endometrial cytology, but may be
indicated by presence of a fluid column greater than 3 mm in diameter
in the uterine lumen. Subclinical endometritis is associated with
reduced first service pregnancy risk, increased days open, and
increased culling risk, making it an extremely costly condition of high
producing dairy cows.
WS01-3
The immune system and the mechanisms of uterine
disease
Sheldon, IM
Royal Veterinary College, London, UK
After parturition, contamination of the uterine lumen by microbes is
ubiquitous in dairy cattle. A third of animals develop clinical disease
and a third have sub-clinical endometritis. Infections cause infertility
by damaging the endometrium, but they also perturb ovarian function.
Effects on the ovary include slower follicle growth, reduced secretion
of oestradiol and fewer ovulations. In animals that ovulate and form a
corpus luteum, there are lower plasma concentrations of progesterone
and uterine disease disrupts luteolysis. The most important pathogens
are Escherichia coli, Arcanobacterium pyogenes and Bovine
Herepesvirus 4 (BoHV-4). Infection with E. coli precedes infection
with A. pyogenes and the development of uterine disease, as well as
being associated with ovarian dysfunction. The endotoxin of E. coli,
lipopolysaccharide (LPS), is found in high concentrations in the
uterine lumen and ovarian follicular fluid of animals with
endometritis. Detection of microbes and their pathogen associated
molecules in the genital tract depends on the innate immune system,
including pathogen recognition receptors such as the Toll-like
Receptors (TLR). Uterine epithelial and stromal cells, and ovarian
granulosa cells express the TLR4, CD14, MD2 receptor complex for
LPS. In vitro, LPS increases the expression of genes associated with
inflammation in endometrial cells, and LPS switches epithelial cell
secretion from prostaglandin F 2α to E 2 , which may explain how
uterine disease disrupts luteolysis. Granulosa cells treated with LPS
have lower aromatase expression and reduced oestradiol production,
which may explain how uterine disease perturbs ovarian follicle
growth and function. Severe uterine pathology is associated with the