Reproduction in Domestic Animals - Facultad de Ciencias Veterinarias
Reproduction in Domestic Animals - Facultad de Ciencias Veterinarias
Reproduction in Domestic Animals - Facultad de Ciencias Veterinarias
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16 t h International Congress on Animal <strong>Reproduction</strong><br />
Workshop Abstracts 5<br />
WORKSHOP ABSTRACTS<br />
Workshop 01 - Pathophysiology and Immunology of<br />
Postpartum Uter<strong>in</strong>e Disease <strong>in</strong> Cattle<br />
Mo<strong>de</strong>rator: Mart<strong>in</strong> Sheldon (UK)<br />
WS01-1<br />
The pathogens and the cause of uter<strong>in</strong>e disease<br />
Földi, J 1,2 ; Pécsi, A 3 ; Szabó, J 4 ; Kulcsár, M 2 ; Egyed, L 5 ; Huszenicza, G 2 *<br />
1Intervet International B.V., Boxmeer, Holland; 2 Faculty of Veter<strong>in</strong>ary Science,<br />
Szt. István University, Budapest, Hungary; 3 Faculty of Agricultural Science,<br />
University of Debrecen, Hungary; 4 Faculty of Medical Science, University of<br />
Debrecen, Hungary; 5 Veter<strong>in</strong>ary Medical Research Institute, Budapest,<br />
Hungary<br />
A wi<strong>de</strong> variety of bacteria are present <strong>in</strong> the uterus of all cows at the<br />
first 10-14 postpartum (pp) days, regardless of disease signs. Mostly<br />
Streptococcus spp., Staphylococcus spp. and Bacillus spp. were<br />
isolated from the uterus of cows with physiological <strong>in</strong>volution, while<br />
Arcanobacterium pyogenes (A. pyo), Escherichia coli (E. coli) and<br />
different Gram negative (GN) anaerobic bacteria namely<br />
Fusobacterium necrophorum, Prevotella spp. and Bacteroi<strong>de</strong>s spp.<br />
were predom<strong>in</strong>ant <strong>in</strong> the uterus of cl<strong>in</strong>ically diseased animals. Series<br />
of studies confirmed that cl<strong>in</strong>ical and reproductive consequences are<br />
associated with these ‘primary uter<strong>in</strong>e pathogen bacteria’. Although<br />
E. coli plays a key role <strong>in</strong> puerperal metritis (up to 14 days pp) i.e.<br />
systemic signs of the disease are endotox<strong>in</strong> mediated, its <strong>in</strong>fluence<br />
<strong>de</strong>creases by the time of <strong>in</strong>volution. Cl<strong>in</strong>ical endometritis/pyometra<br />
is mostly the result of a cha<strong>in</strong> of re-<strong>in</strong>fection with A. pyo and GN<br />
anaerobes. A. pyo acts synergistically with F. necrophorum,<br />
Bacteroi<strong>de</strong>s spp. and Prevotella spp. Isolation of A. pyogenes at the<br />
late <strong>in</strong>volution period (28-35 days) is associated with dramatically<br />
<strong>de</strong>creased re-conception rate.<br />
Bov<strong>in</strong>e herpesvirus type 4 (BoHV-4) is a member of Rhad<strong>in</strong>ovirus<br />
genus with<strong>in</strong> the Gammaherpesvir<strong>in</strong>ae subfamily. BoHV-4 is unique<br />
among the BoHVs concern<strong>in</strong>g its wi<strong>de</strong> tropism of species as well as<br />
tissue distribution <strong>in</strong>clud<strong>in</strong>g reproductive organs. BoHV-4 has been<br />
associated with abortion and (puerperal) metritis s<strong>in</strong>ce 1973, however,<br />
its endometriotropism and the symbiotic relationship between<br />
endometrial stromal cells and macrophages persistently <strong>in</strong>fected with<br />
the virus has most recently been proven. It supports the concept that<br />
BoHV-4, as a secondary pathogen, <strong>de</strong>creases the local immune<br />
response and as such, promotes bacterial metritis.<br />
Presence of pathogens <strong>in</strong> the uterus i.e. (bacterial) contam<strong>in</strong>ation does<br />
not always result <strong>in</strong> <strong>in</strong>flammation. Even the colonization of the entire<br />
uter<strong>in</strong>e wall i.e. (bacterial) <strong>in</strong>fection as such, does not necessarily<br />
mean a cl<strong>in</strong>ical disease; it <strong>de</strong>pends on the immune status of the host.<br />
The course of uter<strong>in</strong>e <strong>in</strong>volution may be consi<strong>de</strong>red as a ‘see-saw<br />
balance’: <strong>in</strong> a physiological situation the self-<strong>de</strong>fence mechanisms are<br />
able to counteract the bacterial and/or viral <strong>in</strong>fection.<br />
On a herd level, the most important risk factors of metritis are:<br />
metabolic disor<strong>de</strong>rs i.e. hyperketonaemia and/or ketonuria,<br />
hypocalcaemia; dystocia, reta<strong>in</strong>ed foetal membranes, manual<br />
<strong>in</strong>tervention at calv<strong>in</strong>g (associated with poor hygiene), herd size,<br />
season, parity, high milk production and lack of graz<strong>in</strong>g.<br />
WS01-2<br />
The host and nature of postpartum uter<strong>in</strong>e disease <strong>in</strong><br />
dairy cows<br />
Gilbert, RO<br />
Cornell University, Ithaca, NY, USA<br />
Fetal membranes are usually expelled with<strong>in</strong> 6 hours after <strong>de</strong>livery<br />
and are regar<strong>de</strong>d as reta<strong>in</strong>ed after 12 or 24 hours. The <strong>in</strong>ci<strong>de</strong>nce <strong>in</strong><br />
dairy cows is about 5 – 15%. Risk of retention is <strong>in</strong>creased by<br />
abortion, stillbirth, low birthweight, multiple birth, premature<br />
parturition, dystocia, heat stress and hypocalcemia. Deficiency of<br />
antioxidant nutrients such as selenium and vitam<strong>in</strong> E is also<br />
implicated. Retention of fetal membranes is associated with impaired<br />
prepartum immune function, particularly with reduced activity of<br />
neutrophils. This impairment extends <strong>in</strong>to the postpartum period and<br />
mediates <strong>in</strong>creased susceptibility to subsequent uter<strong>in</strong>e disease and<br />
mastitis.<br />
Puerperal metritis, characterized by malodorous, red-brown uter<strong>in</strong>e<br />
exudate and uter<strong>in</strong>e atony before 14 days postpartum affects up to<br />
40% of dairy cows <strong>in</strong> some herds. Systemic signs <strong>in</strong>clud<strong>in</strong>g fever,<br />
<strong>de</strong>pression or malaise are <strong>in</strong>consistent. Reduced dry matter <strong>in</strong>take <strong>in</strong><br />
late pregnancy, result<strong>in</strong>g negative energy balance and impaired<br />
immune function contribute to the pathogenesis of this condition as<br />
well as cl<strong>in</strong>ical and subcl<strong>in</strong>ical endometritis. Cows with metritis are at<br />
<strong>in</strong>creased risk for subsequent endometritis. Response to treatment is<br />
generally favorable. Most cows with overt uter<strong>in</strong>e disease do not<br />
ovulate early <strong>in</strong> the postpartum period. Cows ovulat<strong>in</strong>g <strong>in</strong> the face of<br />
cont<strong>in</strong>ued uter<strong>in</strong>e <strong>in</strong>fection may be predisposed to <strong>de</strong>velopment of<br />
pyometra – an accumulation of purulent exudate <strong>in</strong> the uter<strong>in</strong>e lumen<br />
<strong>in</strong> the presence of a persistent corpus luteum.<br />
Cl<strong>in</strong>ical endometritis is best diagnosed and treated after 4 weeks<br />
postpartum when purulent material is <strong>de</strong>monstrable <strong>in</strong> the uterus or<br />
vag<strong>in</strong>a by ultrasonography, vag<strong>in</strong>oscopy, manual <strong>in</strong>spection, or use of<br />
a specifically <strong>de</strong>signed <strong>in</strong>strument (Metricheck®) or if the cervix<br />
rema<strong>in</strong>s larger than 7.5 cm <strong>in</strong> diameter. Presence of these signs is<br />
associated with reduced likelihood of subsequent pregnancy.<br />
Pregnancy risk is <strong>in</strong>creased by treatment with <strong>in</strong>trauter<strong>in</strong>e cephapir<strong>in</strong><br />
or systemic prostagland<strong>in</strong> F2alpha.<br />
Many cows without overt signs of <strong>in</strong>fection have persistent uter<strong>in</strong>e<br />
<strong>in</strong>flammation at the beg<strong>in</strong>n<strong>in</strong>g of the rebreed<strong>in</strong>g period. This<br />
condition is best diagnosed by endometrial cytology, but may be<br />
<strong>in</strong>dicated by presence of a fluid column greater than 3 mm <strong>in</strong> diameter<br />
<strong>in</strong> the uter<strong>in</strong>e lumen. Subcl<strong>in</strong>ical endometritis is associated with<br />
reduced first service pregnancy risk, <strong>in</strong>creased days open, and<br />
<strong>in</strong>creased cull<strong>in</strong>g risk, mak<strong>in</strong>g it an extremely costly condition of high<br />
produc<strong>in</strong>g dairy cows.<br />
WS01-3<br />
The immune system and the mechanisms of uter<strong>in</strong>e<br />
disease<br />
Sheldon, IM<br />
Royal Veter<strong>in</strong>ary College, London, UK<br />
After parturition, contam<strong>in</strong>ation of the uter<strong>in</strong>e lumen by microbes is<br />
ubiquitous <strong>in</strong> dairy cattle. A third of animals <strong>de</strong>velop cl<strong>in</strong>ical disease<br />
and a third have sub-cl<strong>in</strong>ical endometritis. Infections cause <strong>in</strong>fertility<br />
by damag<strong>in</strong>g the endometrium, but they also perturb ovarian function.<br />
Effects on the ovary <strong>in</strong>clu<strong>de</strong> slower follicle growth, reduced secretion<br />
of oestradiol and fewer ovulations. In animals that ovulate and form a<br />
corpus luteum, there are lower plasma concentrations of progesterone<br />
and uter<strong>in</strong>e disease disrupts luteolysis. The most important pathogens<br />
are Escherichia coli, Arcanobacterium pyogenes and Bov<strong>in</strong>e<br />
Herepesvirus 4 (BoHV-4). Infection with E. coli prece<strong>de</strong>s <strong>in</strong>fection<br />
with A. pyogenes and the <strong>de</strong>velopment of uter<strong>in</strong>e disease, as well as<br />
be<strong>in</strong>g associated with ovarian dysfunction. The endotox<strong>in</strong> of E. coli,<br />
lipopolysacchari<strong>de</strong> (LPS), is found <strong>in</strong> high concentrations <strong>in</strong> the<br />
uter<strong>in</strong>e lumen and ovarian follicular fluid of animals with<br />
endometritis. Detection of microbes and their pathogen associated<br />
molecules <strong>in</strong> the genital tract <strong>de</strong>pends on the <strong>in</strong>nate immune system,<br />
<strong>in</strong>clud<strong>in</strong>g pathogen recognition receptors such as the Toll-like<br />
Receptors (TLR). Uter<strong>in</strong>e epithelial and stromal cells, and ovarian<br />
granulosa cells express the TLR4, CD14, MD2 receptor complex for<br />
LPS. In vitro, LPS <strong>in</strong>creases the expression of genes associated with<br />
<strong>in</strong>flammation <strong>in</strong> endometrial cells, and LPS switches epithelial cell<br />
secretion from prostagland<strong>in</strong> F 2α to E 2 , which may expla<strong>in</strong> how<br />
uter<strong>in</strong>e disease disrupts luteolysis. Granulosa cells treated with LPS<br />
have lower aromatase expression and reduced oestradiol production,<br />
which may expla<strong>in</strong> how uter<strong>in</strong>e disease perturbs ovarian follicle<br />
growth and function. Severe uter<strong>in</strong>e pathology is associated with the