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Endometriosis affects a large percentage of the rhesus macaques (Macaca mulatta) at our institution. When the disease is diagnosed in macaques on long-term research protocols, the treatment of choice in our facility is monthly administration of medroxyprogesterone acetate (MPA) to decrease estrogen release and subsequently diminish clinical signs associated with the disease. Because hormonal fluctuations associated with the normal menstrual cycle are known to affect parameters of glucoregulatory function in rhesus macaques, we evaluated the effect of MPA treatment on glucoregulatory function cross-sectionally in 6 animals and longitudinally in 4 animals with endometriosis. Our hypothesis was that monthly administration of MPA for the treatment of endometriosis would negatively affect glucoregulatory function in rhesus macaques. We found that adult female rhesus macaques on MPA therapy for 1.4 to 36.1 mo had lower insulin sensitivity than did age- and weight-matched healthy control animals. In addition, glucoregulatory function was reduced after MPA treatment as compared with pretreatment levels in a group of 4 macaques. These data suggest that glucoregulatory function should be considered when endometriosis treatment is planned for rhesus macaques.

The aim of the present study was to characterize the morpho-functional features of endometrosis in barren and foaling mares, using both conventional histopathological and immunohistochemical methods. Endometrial biopsy samples were collected during the physiological breeding season from 159 estrous, clinically healthy mares (mean age 12 years), and the quality and degree of endometrosis was histomorphologically defined. The mares were bred and those that foaled were put in the foaling group whereas those that did not foal were placed in the barren group. Foaling mares were then compared with barren mares. Sixty-four percent (101/159) of uterine samples showed varying degrees of endometrosis and were used for this study. The sample population consisted of 51 barren and 50 foaling mares suffering from endometrosis. Expression of steroid hormone receptors (estrogen receptor, progesterone receptor) and endometrial protein secretion patterns (uteroglobin [UG], uterocalin [UC], calbindin(D9k) [CAL], uteroferrin [UF]) was evaluated by immunohistochemistry (barren mares N = 51, foaling mares N = 31). In comparison with unaffected glands, fibrotic glands generally showed a cycle-asynchronous, partially patchy protein expression pattern which is interpreted as a sign of endometrial maldifferentiation within fibrotic areas. In barren mares (N = 51) more than half of biopsy samples (27/51) showed a destructive mostly moderate (20/27) type of endometrosis. In affected glands, staining for UG (17/21) was decreased (P < 0.001). Foaling mares (N = 50) frequently showed a mild, nondestructive endometrosis (35/50). Compared with barren mares, foaling mares had statistically (P < 0.05) more often a cycle-synchronous or increased UG expression pattern within fibrotic glands. Obvious deviations of either UG or UC rarely occurred. Within fibrotic foci, UF often demonstrated a cycle-synchronous or more intense expression pattern in both foaling (28/31) and barren mares (41/51), compared with healthy glands. Mares of both groups showed a cycle-asynchronous staining for estrogen receptor and progesterone receptor in the stromal cells in areas of periglandular fibrosis and the glandular epithelia. These findings indicate that affected areas become independent of the uterine control mechanisms and exhibit specific differentiation dynamics. Immunohistochemical investigations showed that the secretory patterns differ between barren and foaling mares. The findings in this study should be considered as a useful addition to the "classical" Kenney categorization., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: As common marmosets (Callithrix jacchus) are frequently used experimental animals, sensitive test systems are needed to evaluate impairment and pain caused by procedures and diseases., Methods: A diurnal profile of healthy animals was obtained by videotaping. Differences in social behavior and cognitive skills between marmosets with established endometriosis and healthy monkeys were investigated using the videotaping, the Wisconsin General Test Apparatus (WGTA), and a food tree., Results: The marmosets showed a mostly trimodal course of activity. Social grooming and activity were significantly decreased in animals with endometriosis; furthermore, the diseased monkeys habituated significantly worse to the cognitive test settings. The food tree experiments offered no differences between diseased and control animals., Conclusion: The videotaping and the WGTA are suitable methods to detect disease-related impairments in common marmosets, which is essential for the refinement of experiments., (© 2011 John Wiley & Sons A/S.)

The present investigation was intended to show a different immunohistochemical profile of matrix metalloproteinase-2 and Tissue inhibitor metalloproteinase-2 in bovine uteri with adenomyosis during follicular phase. Uterine samples of 32 cows in reproductive age were taken from the medial third of one of the uterine horns and grouped according to the adenomyosis degree (superficial and deep). Tissue sections (4 μm) were incubated overnight at 4°C with monoclonal antibody for matrix metalloproteinase-2 and Tissue inhibitor metalloproteinase-2. Staining intensities were evaluated in the luminal epithelium, ectopic and dystopic endometrial tissue (stroma, capillaries and glands), endometrial-myometrial border, myometrium, myometrial vessels (middle tunic and endothelium). The matrix metalloproteinase-2 expression was higher for deep adenomyosis samples, showing a differential mean reactivity in superficial endometrium, myometrial vessels, myometrium adjacent to adenomyotic focus and endometrial-myometrial border (P < 0.05). Moreover, matrix metalloproteinase-2 expression was higher in deep adenomyosis samples than that of Tissue inhibitor metalloproteinase-2 in almost all uterine structures analyzed (except for the endometrial and myometrial vessels and endometrial-myometrial border). The opposite was observed in the follicular phase, for both normal specimens and with superficial adenomyosis, where Tissue inhibitor metalloproteinase-2 expression was higher than that of matrix metalloproteinase-2. In conclusion, a differential pattern of matrix metalloproteinase-2 and Tissue inhibitor metalloproteinase-2 was observed in cow uteri with adenomyosis.

Escherichia coli are believed to be associated with postpartum metritis and endometritis but their role in the pathogenesis of both diseases is still undefined. In this study, uterine swabs for E. coli isolation were collected from 374 lactating Holstein cows housed on 4 commercial farms near Ithaca, New York. A total, 125 of 374 cows (33.4%) were positive for E. coli culture. Standard multiplex PCR protocols were used to screen the isolates for the presence of 32 virulence factor genes. Cows that had twin parturition were 4.4 times more likely to have intrauterine E. coli contamination than those that gave birth to single live female calves. Stillborn parturition and birth of single live male calves also increased the odds of intrauterine contamination by E. coli (3.7- and 1.6-fold, respectively) compared with birth of live female calves. Six virulence factors, common to extraintestinal and enteroaggregative E. coli, were found to be associated with metritis and endometritis: fimH, hlyA, cdt, kpsMII, ibeA, and astA. The virulence factor gene fimH was the most prevalent and the most significant: intrauterine E. coli carrying fimH and at least 1 of the other 5 identified virulence factors were pathogenic, and phylogenetic analysis based on the nucleotide sequence of DNA gyrase from 41 such IUEC revealed 2 clades., (Copyright © 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Uterine microbiology, antimicrobial susceptibility and endometrial cytology were investigated in a total of 51 mares with fertility problems from 16 different stud farms in Serbia. Uterine cultures were performed after collection with a double guarded uterine swab, and endometrial cytology was evaluated after collection of endometrial cells with a special device (cytology brush). In 21 of 51 mares, at least one bacterial species was isolated from the uterus; the most frequent were Streptococcus equi subsp. zooepidemicus (13 isolates) and E. coli (four isolates). All isolates of Streptococcus equi subsp. zooepidemicus were susceptible to penicillin. Results from endometrial cytology were inconsistent; in 17 animals with positive bacteriological culture, cytology was not altered. It can be concluded that in Serbia, as in many other contries, Streptococcus equi subsp. zooepidemicus is the main cause for equine endometritis. It can be easily diagnosed by uterine culture but endometrial cytology does not always prove the existence of an endometrial infection with this agent.

Pharmacokinetics and milk levels of ceftriaxone were studied in healthy and endometritic cows following single intravenous administration. The drug was detected up to 8 h of dosing in plasma of healthy and endometritic cows and the drug disposition followed three-compartment open model. The values of Vd(area), AUC, t(1/2beta), Cl(B), MRT and P/C ratio were 0.50 +/- 0.19 L.kg(-1), 62.2 +/- 23.3 microg.ml(-1).h, 1.02 +/- 0.07 h, 0.30 +/- 0.09 L.kg(-1).h(-1), 1.55 +/- 0.25 h and 0.52 +/- 0.27, respectively, in healthy and 1.55 +/- 0.52 L.kg(-1), 37.0 +/- 17.1 microg.ml(-1).h, 1.56 +/- 0.25 h, 0.56 +/- 0.14 L.kg(-1).h(-1), 2.14 +/- 0.34 h and 1.44 +/- 0.60, respectively, in endometritic cows. The drug was detected in milk for 36 h after administration. For MIC(90) of 0.5 microg.ml(-1) the most appropriate dosage for ceftriaxone, would be 9.0 mg.kg(-1) repeated at 6 h intervals for the treatment of endometritis in cows.

The current report describes an unusual presentation of uterine endometrial polyp with severe hemorrhage and cystic endometrial hyperplasia-pyometra complex in a 9.5-year-old female Doberman Pinscher. The dog presented with a 2-day history of bloody discharge from the vulva and an enlarged abdomen. The postmortem examination revealed a markedly distended right uterine horn with a large pedunculated mass (17 cm x 9 cm x 4 cm) and blood. Based on the histological findings, the diagnosis of uterine endometrial polyp was made.

The aim of the present study was to conduct a semiquantitative immunohistochemical investigation into the levels of intermediary proteins within the nuclear factor (NF)-kappaB pathway throughout the menstrual cycle in a non-human primate, namely the baboon (Papio anubis), with and without endometriosis. Formalin-fixed eutopic (n = 2-4) and ectopic (n = 6-7) endometrial tissues from baboons at the mid-luteal phase were embedded in paraffin and examined for NF-kappaB pathway components (i.e. IkappaB kinase (IKK) alpha, IKKbeta, phosphorylated (phospho-) IkappaBalpha and phospho-NF-kappaB p65 subunit), ubiquitin, 19S proteasome and the NF-kappaB activator tumour necrosis factor (TNF)-alpha. Similarly, endometrial tissues from baboons at the late follicular, mid-luteal and menses phase (n = 2-4) were investigated to determine the levels of these proteins throughout the menstrual cycle. Cytoplasmic stromal IKKalpha and glandular 19S proteasome immunostaining was elevated in the ectopic endometrium, whereas levels of ubiquitin, phospho-p65, IKKbeta, TNF-alpha and nuclear 19S proteasome were similar in the eutopic and ectopic endometrium. A significant decrease in phospho-IkappaBalpha nuclear immunostaining was observed within glandular cells of the ectopic endometrium. In the eutopic endometrium, IKKalpha, ubiquitin and 19S proteasome immunostaining was elevated in different phases of the menstrual cycle, whereas levels of phospho-p65, IKKbeta, phospho-IkappaBalpha and TNF-alpha remained unchanged. We have demonstrated that, in the baboon endometriosis model, levels of IKKalpha immunostaining are elevated, whereas those of phospho-IkappaBalpha are reduced, consistent with the hypothesis that excessive NF-kappaB activity plays a role in reducing ectopic endometrial apoptosis, which contributes to the pathophysiology of endometriosis. Further studies are required to confirm a causal association between elevated IKKalpha levels and reduced endometrial apoptosis.

A 7-yr-old African wild dog (Lycaon pictus) multiparous bitch experienced severe dystocia and death one day after the onset of parturition. Necropsy revealed three placental attachments in the right uterine horn and one in the left. A full-thickness rupture of the right horn at the middle placental attachment and an autolysed fetus free in the abdomen were present. Death was attributed to hypovolemic and endotoxemic shock after uterine rupture. Myometrium adjacent to the rupture and in the left uterine horn was subdivided into irregular pseudolobules by fibrous connective tissue tracts containing small endometrial glandular acini suggestive of adenomyosis, which may have facilitated uterine rupture. This is the first reported case of dystocia-induced uterine rupture and of adenomyosis in a wild dog.

A total of 501 dairy cows were allocated sequentially to be treated immediately after parturition with either 25 iu oxytocin or 35 mg carbetocin, or to be left untreated. Any abnormal parturition, including assisted calving, the birth of twins or dead calves, retained fetal membranes or hypocalcaemia, was recorded, and the cows were examined between 28 and 42 days after calving for endometritis. Pregnancy was diagnosed from 30 days after insemination. The incidence of endometritis was similar (14 per cent, 16 per cent and 19 per cent) and the median intervals from calving to pregnancy were similar (118, 121 and 119 days) for the cows treated with oxytocin, carbetocin or receiving no treatment, respectively. The incidence of endometritis and the median intervals from calving to pregnancy were also similar between the groups for the cows that had an abnormal parturition.

A total of 220 cows and heifers were treated with 3 mg/kg ketoprofen immediately after calving and 24 hours later, and 227 were left untreated as controls. The treated animals tended to have a lower incidence of retained fetal membranes and were 1.7 times less likely to develop the condition than the untreated animals. The treatment did not affect the incidence of milk fever, the endometritis score or the presence of a corpus luteum by 20 to 25 days after calving, and did not affect the cows' early lactation milk yield. There was no particular level of dystocia or periparturient conditions other than retained fetal membranes for which there might be a reproductive or productive advantage following the use of ketoprofen. The intervals from calving to first insemination or to pregnancy, the numbers of inseminations per pregnancy and the pregnancy rate to first insemination were also unaffected by ketoprofen treatment.

Ninety autumn-calving Holstein dairy cows (45 primiparous and 45 multiparous; mean parity, 3.1) were allocated to 1 of 3 treatments; 173, 144, or 114 g of crude protein (CP)/kg of dry matter (DM) from calving until d 150 of lactation. On d 151 of lactation, half the animals receiving 114 g of CP/kg of DM went onto 144 g of CP/kg of DM, half of the animals receiving 144 g of CP/kg of DM went onto 173 g of CP/kg of DM, and half of the animals receiving 173 g of CP/kg of DM went onto 144 g of CP/kg of DM, with the remaining animals staying on their original treatments. This resulted in 6 treatments in mid to late lactation: 114/114; 144/144; 173/173; 114/144; 144/173; and 173/144 g of CP/kg of DM. Overall, 95.3% of cows intended for breeding conceived during a 6-mo breeding period. The average pregnancy rates to first service and first plus second service were 30.9% [standard error of the difference (SED), 0.05] and 56.7% (SED, 0.05) respectively. The average 100 d in-calf rate from the start of the breeding period was 70.5%, and at least one abnormal progesterone profile was observed in 62% of animals. An increase in dietary protein content decreased the requirement for treatment of metritis. There was no effect of dietary protein content on any of the reproductive or progesterone measures; for example, days to conception, calving interval, 100 d in-calf rate (from commencement of breeding), days to onset of luteal activity, average luteal phase, average interovulatory interval, or average interluteal interval. An increase in dietary protein content decreased the average daily energy balance. A more positive energy balance was associated with an increased requirement for the treatment of metritis in the current study. Cumulative energy balance was positively associated with conception. There was no effect of the concentration of plasma urea on any of the reproductive variables; however, the concentration of serum leptin was favorably associated with the time to progesterone increase above 3 ng/mL, which has been deemed essential for embryo survival. Additionally, the average peak concentration of progesterone and the duration of the average luteal phase were favorably associated with the interval from calving to conception. The latter relationships emphasize the importance of progesterone in achieving and maintaining pregnancy.

This paper describes the histomorphological and immunohistochemical characterisation of phenotypic variations of endometrosis as well as potential etiological factors which may influence disease progression. In total, 779 endometrial biopsies were examined. These biopsies were taken in the breeding and non-breeding season (n=509), on defined days during the estrous cycle (n=70) and before and after experimentally induced bacterial endometritis (n=200). In addition to conventional histopathology, selected biopsies were investigated using alcianblue staining as well as immunohistochemical methods for the detection of steroid hormone receptors, Ki-67-antigen, vimentin, desmin, fibronectin, smooth-muscle-alpha-actin and laminin. The equine endometrosis can be divided into a destructive and a non-destructive form. Based on the morphology of the stromal cells involved, an active or inactive state can be distinguished in fibrotic foci. In all types of endometrosis, fibrotic stromal cells show a distinctly reduced expression of steroid hormone receptors in comparison to the intact stroma, indicating their dedifferentiation. However, the steroid hormone receptor expression of involved glandular epithelia seems to depend on the activity of the fibrosis. These results suggest an independency of all fibrotic foci from the hormonal control mechanism of the uterus. The characteristical features of destructive endometrosis are a large number of smooth-muscle-alpha-actin containing myofibroblasts, a pronounced epithelial vimentin expression, excessive extracellular matrix accumulation and a progressive alteration of the basal lamina. Furthermore, the frequently seen cystic glandular dilatation and mechanical destruction of the uterine glands may occur due to the contractibility of the myofibroblasts involved. As shown in this study, a simultaneous endometritis can cause a temporary activation of fibrotic stromal cells. However, cyclic and seasonal endocrine changes seem to have no effects on progression of the disease. It can be concluded that the various types of endometrosis represent different stages in the fibrotic process, possibly leading to the destruction of the glands and subsequently resulting in the development of a stromal fibrosis.

The purpose of this study was to determine whether haptoglobin (Hp) could be used as a predictive measure for metritis. Cattle were grouped into 3 health categories based on the condition of vaginal discharge and body temperature after calving: severe metritis (n = 12), mild metritis (n = 32), and healthy (n = 23). Blood was collected and analyzed for Hp concentration on d -20 +/- 5, -6 +/- 2, -2 +/- 1, and d 0 relative to calving, and then every 3 d after calving until d +21. Cows with mild and severe metritis had greater Hp concentrations than healthy cows between d 0 and d +12. Mean (+/-SE) Hp concentrations peaked on d +3 in the cows with mild metritis (1.06 +/- 0.15 g/L) and on d +6 in cows with severe metritis (1.62 +/- 0.47 g/L). Mean concentrations for the healthy group were 0.58 +/- 0.12 g/L and 0.31 +/- 0.08 g/L on d +3 and d +6, respectively. Clinical signs of pathological discharge for the mildly and severely metritic cows did not occur until, on average, 8.6 +/- 3.9 d and 5.3 +/- 1.9 d after calving, respectively. Cows with Hp concentrations >or=1 g/L on d +3 were 6.7 times more likely to develop severe or mild metritis; this predictive threshold has a sensitivity of 50% and specificity of 87%. These results indicate that an acute phase inflammatory response precedes clinical metritis and that Hp screening may assist in the early detection of metritis, providing increased opportunities for early treatment and prevention.

Data from 1,010 lactating lactating, predominately component-fed Holstein cattle from 25 predominately tie-stall dairy farms in southwest Ontario were used to identify objective thresholds for defining hyperketonemia in lactating dairy cattle based on negative impacts on cow health, milk production, or both. Serum samples obtained during wk 1 and 2 postpartum and analyzed for beta-hydroxybutyrate (BHBA) concentrations that were used in analysis. Data were time-ordered so that the serum samples were obtained at least 1 d before the disease or milk recording events. Serum BHBA cutpoints were constructed at 200 micromol/L intervals between 600 and 2,000 micromol/L. Critical cutpoints for the health analysis were determined based on the threshold having the greatest sum of sensitivity and specificity for predicting the disease occurrence. For the production outcomes, models for first test day milk yield, milk fat, and milk protein percentage were constructed including covariates of parity, precalving body condition score, season of calving, test day linear score, and the random effect of herd. Each cutpoint was tested in these models to determine the threshold with the greatest impact and least risk of a type 1 error. Serum BHBA concentrations at or above 1,200 micromol/L in the first week following calving were associated with increased risks of subsequent displaced abomasum [odds ratio (OR) = 2.60] and metritis (OR = 3.35), whereas the critical threshold of BHBA in wk 2 postpartum on the risk of abomasal displacement was >or=1,800 micromol/L (OR = 6.22). The best threshold for predicting subsequent risk of clinical ketosis from serum obtained during wk 1 and wk 2 postpartum was 1,400 micromol/L of BHBA (OR = 4.25 and 5.98, respectively). There was no association between clinical mastitis and elevated serum BHBA in wk 1 or 2 postpartum, and there was no association between wk 2 BHBA and risk of metritis. Greater serum BHBA measured during the first and second week postcalving were associated with less milk yield, greater milk fat percentage, and less milk protein percentage on the first Dairy Herd Improvement test day of lactation. Impacts on first Dairy Herd Improvement test milk yield began at BHBA >or=1,200 micromol/L for wk 1 samples and >or=1,400 micromol/L for wk 2 samples. The greatest impact on yield occurred at 1,400 micromol/L (-1.88 kg/d) and 2,000 micromol/L (-3.3 kg/d) for sera from the first and second week postcalving, respectively. Hyperketonemia can be defined at 1,400 micromol/L of BHBA and in the first 2 wk postpartum increases disease risk and results in substantial loss of milk yield in early lactation.

Although alterations in patterns of protein secretion revealed in uterine flushings from mares suffering from endometrosis have been described, little is known about alterations at the cellular level. Hence, the aim of this study was to characterize deviations in patterns of uterine gland secretion patterns using endometrial biopsies, histochemical and newly established immunohistochemical methods. Forty-eight endometrial biopsies were obtained from mares suffering from various types of endometrosis (active and inactive, destructive and non-destructive) and degree (mild to severe) were analyzed for expression of the proteins uteroglobin, uteroferrin, calbindinD9k and uterocalin as representatives of endometrial proteins detectable by immunohistochemistry using polyclonal antibodies. Glycogen was identified using the PAS-reaction and mucopolysaccharides were stained with alcian blue. Uterine glandular epithelia within fibrotic foci mostly revealed a protein and carbohydrate pattern of expression which was independent of hormonal changes during the estrous cycle. In comparison to non-affected glands, most epithelial cells within periglandular fibrosis exhibited decreased immunostaining intensity for proteins, especially when there was destructive endometrosis. However, uteroferrin staining intensity was strong within areas of severe destructive endometrosis. Moreover, only few basal glandular epithelial cells, especially those in cystic glands, stained for mucopolysaccharides that are typically seen within the luminal epithelia. Usually a single fibrotic focus caused only slight alterations in glandular proteins and carbohydrate reaction patterns, so that only more severe endometrosis lead to deviations which were detectable in uterine flushings. The highly sensitive methods used in the present study allow studies of uterine secretion patterns in the context of routine assessment of endometrial biopsies.

A 48-year-old, multiparous, female hybrid orang-utan (Pongo abelii/pygmaeus) was investigated after a 3-year history of irregular and excessively heavy menstrual bleeding. Opportunistic pelvic examinations over a 2.5-year period were non-diagnostic. Medical therapy was not effective. A subtotal hysterectomy with bilateral salpingo-ovariectomy was performed. A pedunculated mass spanning 90% of the uterine lumen was seen grossly, and histopathology confirmed uterine adenomyosis. Adenomyosis is defined as the ectopic occurrence or diffuse implantation of endometrial tissue, including glands and stroma, into the myometrium. It is common in older, usually premenopausal, multiparous women and is frequently associated with other uterine pathology, including endometrial hyperplasia and leiomyomas. The most common clinical signs are dysmenorrhoea and heavy menstrual bleeding; however, up to 35% of women are asymptomatic. Diagnosis is difficult and requires myometrial sampling and an experienced pathologist. A hysterectomy in this case was diagnostic and curative. There have been few reports of uterine adenomyosis in non-human primates and none reported in an orang-utan. Uterine adenomyosis should be considered in the differential diagnosis in any multiparous, aged, non-human female primate with irregular and excessively heavy menstrual bleeding, and hysterectomy with bilateral salpingo-ovariectomy is recommended as a diagnostic and therapeutic solution.

Arcanobacterium pyogenes is considered to be the most relevant bacterium involved in the establishment of puerperal uterine infection in cattle due to its persistence in utero, resistance to treatment and synergic action with Gram negative anaerobes. Once the infection is established, A. pyogenes is responsible for the persistence of the infection. The objective of this study was to characterize A. pyogenes field isolates recovered from the uterus of cows with either normal puerperium or clinical metritis, in an attempt to identify factors that might be associated with the establishment and persistence of the disease. This characterization was based on BOX-PCR typing and on screening of eight virulence factor genes (plo, nanP, nanH, cbpA, fimA, fimC, fimE, fimG) by conventional PCR. Finally, a relationship between clonal types, virulence factors and presence of disease was investigated. A. pyogenes clonal types identified from isolates recovered from the uterus of postpartum dairy cows differed among herds. Although some clonal types were strictly associated with the development of clinical metritis, others were identified from isolates recovered from normal puerperium and clinical metritis cows. Moreover, the presence of the eight virulence factor genes was not related with the ability to induce clinical metritis, suggesting that the type of A. pyogenes may not be a determinant factor in the development of the disease. We suggest that host intrinsic factors, the synergism between A. pyogenes and other bacteria and the differential gene expression of virulence factor genes may play a more relevant role in the establishment of puerperal uterine infections.

The endometrium undergoes marked functional changes during estrous cycle and pregnancy. As the adjacent environment of the conceptus, it represents the maternal interface for embryo-maternal communication, which is essential to maintain pregnancy. Transcriptome studies provide the unique opportunity to assess molecular profiles changing in response to endocrine or metabolic stimuli or to embryonic pregnancy recognition signals. Here we review the current state of transcriptome profiling techniques and the results of a series of transciptome studies comparing bovine endometrium samples during the estrous cycle or endometrium samples from pregnant vs. non-pregnant animals. These studies revealed specific mRNA profiles which are characteristic for the functional status of the endometrium. Transcriptome studies of endometrial samples recovered during the pre-attachment period identified many interferon-stimulated genes, genes that are possibly involved in embryo-maternal immune modulation ( C1S, C1R, C4, SERPING1, UTMP, CD81, IFITM1, BST2), as well as genes affecting cell adhesion ( AGRN, CD81, LGALS3BP, LGALS9, GPLD1, MFGE8, and TGM2) and remodeling of the endometrium ( CLDN4, MEP1B, LGMN, MMP19, TIMP2, TGM2, MET, and EPSTI1). The results of these transcriptome studies were compared to those of similar microarray analyses in human, mouse and Rhesus monkey to identify similarities in endometrial biology between mammalian species and species-specific differences. Future studies will cover dynamic transcriptome changes between different stages of early pregnancy, the relationship between metabolic problems in dairy cows and the functionality of reproductive tissues as well as endometrium transcriptome profiles in recipients of somatic cell nuclear transfer embryos.

A 12-year-old, female Siamese cat with a long-term history of megestrol acetate treatment for suppression of estrus was presented with vomiting and abdominal pain. Uterine adenomyosis was diagnosed after an ovariohysterectomy.

Objective: To evaluate the mechanism of action of recombinant human tumor necrosis factor (TNF)-binding protein-1 by assessing differential expression of messenger RNA (mRNA) for cytokines, matrix metalloproteinases, and growth and adhesion factors in baboons., Design: Analysis of gene expression in a prospective randomized study., Setting: University Fertility Center., Animal(s): In the in vivo study, 14 baboons were randomly and subcutaneously (SC) treated with either phosphate-buffered saline (PBS), GnRH antagonist, or recombinant human TNF-binding protein-1 at the time of induction. In the ex vivo study, 4 baboons were treated by menstrual endometrium that had been incubated randomly with either PBS or recombinant human TNF-binding protein-1 before intrapelvic injection., Intervention(s): In the in vivo study, analysis of 11 endometrial and 10 endometriosis biopsies included either PBS (n = 5), GnRH antagonist (n = 8), or recombinant human TNF-binding protein-1 (n = 8). In the ex vivo study, 2 endometrial and 4 endometriosis biopsies were analyzed from 4 baboons., Main Outcome Measure(s): The mRNA expression of TNF-alpha, IL-8, IL-6, transforming growth factor-beta (TGF-beta), vascular endothelial growth factor, intercellular adhesion molecule-1, matrix metalloproteinase-1, and regulated on activation, normal T-cell expressed and secreted were investigated using real-time reverse transcriptase-polymer chain reaction (PCR)., Result(s): TGF-beta mRNA expression was decreased in endometriotic lesions from baboons treated with recombinant human TNF-binding protein-1 when compared with the placebo group., Conclusion(s): Except TGF-beta, mRNA expression of inflammatory cytokines and adhesion/growth factors is not affected in endometrial and endometriosis biopsies from baboons after induction of endometriosis combined with either systemic injection of recombinant human TNF-binding or GnRH antagonist or ex vivo treatment with recombinant human TNF-binding protein-1. Further studies are needed to elucidate the mode of action on how inhibition of TNF-alpha activity prevents the development of endometriosis.

Background: Endometriosis is a condition where endometrium-like tissue forms lesions at ectopic sites outside the uterus. In women, oral contraceptive pills and progestins are often prescribed as therapy for early stage endometriosis. In contrast, in macaques the disease is frequently advanced at the time of diagnosis and ovariectomy is the standard therapy. However, surgery is contraindicated in many patients. A review of 15 endometriosis cases over the past 10 years at the Oregon National Primate Research Center (ONPRC) revealed that 5 failed to show improvement after ovariectomy and were subsequently euthanized. Therefore, our goal was to assess the feasibility of treating endometriosis in macaques with chronic progesterone (P) as an alternative therapy for the disease., Methods: Seven adult rhesus macaques with advanced endometriosis were identified by clinical symptoms and endometriosis was confirmed by abdominal palpation, ultrasound examination, and/or aspiration of menstrual blood from abdominal cysts. The patients were chronically treated with Silastic capsules that released 5-7 ng P /ml in blood for up to 20 months. During treatment the patients were assessed daily and scored numerically for appetite, activity, attitude, abdominal discomfort and menstruation by the Clinical Veterinary staff. The patients were then re-examined by abdominal palpation and ultrasound for the disease at the end of treatment., Results: During the first 2 weeks of treatment, endometriotic symptoms improved significantly in all the patients (P < 0.05). This was associated with a significant increase in body weight and significant reduction in abdominal discomfort and menstrual bleeding. Two of the patients gradually developed increased symptoms of the disease after 5 months of treatment. Post-treatment abdominal examination revealed that 2/5 patients continued to have an abdominal mass even though symptoms were suppressed., Conclusions: We conclude that continuous P treatment of rhesus monkeys provides therapeutic benefit to reduce symptoms of endometriosis and may provide an option for cases where ovariectomy is contraindicated.

Background: Spontaneous reproductive tract abnormalities occurred in six female wild-caught, Philippine-origin, Macaca fascicularis. These animals were between 19 and 22 years of age and maintained in captivity for approximately 15 years. Clinical presentations ranged from asymptomatic to painful menses manifested as cyclical recumbency and lethargy. All animals had masses in the caudal ventral abdomen., Methods: Diagnostics included physical examination, complete blood counts, clinical chemistries, radiography, and ultrasonography. All animals had an ovariosalpingohysterectomy., Results: Histologic diagnoses included ovarian granulosa cell tumor, ovarian pseudocystic cavitation with encapsulating fibrosis, uterine smooth muscle hyperplasia, uterine leiomysarcoma, and uterine leiomyoma with possible adenomyosis., Conclusions: The abnormalities discovered in these animals present novel insight into the reproductive diseases prevalent in geriatric female M. fascicularis, which vary from that previously reported in other non-human primate species.

The aim of the present study was to estimate the absorption of 125I-labeled proinflammatory cytokines--interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) from inflamed porcine uterus into the uterine venous blood. Moreover, in order to test the hypothesis that the above cytokines penetrate directly into ovaries and oviduct via local destination transfer in the area of the ovarian vascular pedicle and bypassing the systemic circulation, the concentration of IL-1beta, IL-6 and TNF-alpha in ovarian and oviductal tissues was also studied. These cytokine concentrations were also estimated in the ovarian venous blood. IL-1beta, IL-6 and TNF-alpha from both control and inflamed uteri were absorbed into the uterine venous blood, but it was higher (P < 0.05-0.001) from the pathologically changed uteri. The uterine tissues, particularly the endometrium, of both control and inflamed uteri retained all studied cytokines, but to a higher degree (P < 0.001) in the inflamed uteri. Injections of IL-1beta, IL-6 and TNF-alpha into the control and inflammatory changed uteri produced the presence of these proteins in the ovary and oviduct. However, the concentrations of IL-1beta and IL-6 in the ovarian and oviductal tissues was low after injections of control and inflamed uteri with these cytokines. In turn, administration of TNF-alpha into the inflammatory changed uteri lead to an enhancement in the concentration of this cytokine in the ovarian parenchyma (P < 0.05) and oviduct (P < 0.001). All studied cytokines were found in the ovarian venous blood after their injection into both control and inflamed uteri, which indicated its local destination transfer to the ovary. However, the concentration of cytokines increased (P <0.05-0.001) in the gilts with pathologically changed uteri as compared to controls. The study showed that both control and inflamed porcine uteri absorbed IL-1beta, IL-6 and TNF-alpha into the uterine venous blood, but the values of absorbed cytokines from inflamed uteri were higher. Moreover, the quantity and the manner of the studied cytokineS absorption into the uterine venous blood differed.

Adenomyosis is a non-neoplastic condition characterized by the presence of ectopic endometrium in the myometrium with hyperplasia of adjacent smooth muscle. Common symptoms in women include debilitating pelvic pain and abnormal uterine bleeding, and the condition has been paradoxically associated with both multiparity and subfertility. Adenomyosis spontaneously occurs in humans and some non-human primates, including the baboon and macaque, where it has been associated with primary infertility and the presence of endometriosis. No cases of adenomyosis have been previously reported in Pongidae such as gorilla, orangutan or chimpanzee. We here describe two cases of naturally occurring adenomyosis in the chimpanzee (Pan troglodytes) and briefly review the literature regarding the presence of adenomyosis in non-human primate species.

The objectives of this study were as follows: 1) to evaluate the association among abnormal calving, parity, and season on the incidence of puerperal metritis (PM) and clinical endometritis (CE) during d 3 to 13 and 20 to 30 postpartum, respectively; 2) to describe the rectal temperature (RT) of cows with PM before diagnosis; and 3) to document associations among PM, CE, and reproductive performance in lactating dairy cows. This study followed a prospective observational study design. Cows were classified as having an abnormal calving status (AC), i.e., cows calving with dystocia, twins, retained fetal membranes, or some combination of these conditions, and having a normal calving status (NC). Daily RT was recorded from d 3 to 13 postpartum for all cows, and health examinations were performed on cows that appeared not well. A total of 450 calvings were evaluated. Cows with an AC had greater odds of PM than cows with NC [adjusted odds ratio (AOR) = 4.8; 95% confidence interval (CI) = 2.9 to 8.0). A season by parity interaction showed that primiparous cows that calved during the warm season had lower AOR of PM than during the cool season (0.24; 95% CI = 0.09 to 0.62), whereas multiparous cows did not have seasonal effects on PM (1.43; 95% CI = 0.65 to 3.18). Cows with AC have greater AOR for CE than cows with NC (2.8; 95% CI = 1.7 to 4.9), and greater AOR of CE were detected in cows diagnosed with PM than in cows without PM (2.2; 95% CI = 1.1 to 3.9). Rectal temperature in cows with PM increased significantly 24 h before diagnosis of PM, reaching 39.2 +/- 0.05 degrees C on the day of diagnosis. In cows with PM and fever at diagnosis, the RT began to increase from 72 to 48 h before the diagnosis of PM and continued to increase to 39.7 +/- 0.09 degrees C on d 0 (day of diagnosis). Nonetheless, cows with PM without fever at diagnosis had no daily increases in RT before diagnosis of PM. Still, the RT on d 0 was different from cows without PM. Cows without PM had a stable RT (38.6 +/- 0.01 degrees C). There were no detected differences in first-service conception risk or cumulative pregnancy risk by 150 d postpartum between cows with or without PM. Still, a season effect on first-service conception AOR (warm vs. cool = 0.98; 95% CI = 0.18 to 0.72) and accumulated pregnancy AOR by 150 d postpartum was detected (warm vs. cool = 0.18; 95% CI = 0.10 to 0.33).

The baboon is an established model for endometriosis research. This report describes the occurrence of spontaneous endometriosis involving the ileocaecal junction and associated regional lymph nodes in the baboon. All endometriotic foci lacked the nuclear atypia, abnormal mitotic activity and altered nuclear-to-cytoplasmic ratio typical of malignancy. These findings are identical to reports in the human in which ileocaecal and colonic endometriosis is associated with endometriosis in pericolonic and mesenteric lymph nodes. The similarity between baboon and human colonic endometriosis in both location and pathology is striking and lends further evidence supporting the validity of the baboon as a model for human endometriosis.

Background: Endometriosis is one of the most common causes of infertility and pelvic pain. A baboon model has recently been developed whereby the intrapelvic injection of menstrual endometrium results in the induction of endometriotic lesions. We have used this model to investigate changes in ultrastructure and glycosylation of endometria from normal and diseased baboons., Methods: Endometriosis was induced in eight female baboons; endometrial tissue and endometriotic lesions were removed on days 9-11 post ovulation between 3 and 16 months of disease and compared with endometrium from 17 control animals, using electron microscopy and lectin histochemistry., Results: Ultrastructurally, diseased endometrial glands showed abnormalities in secretory vacuoles and an intracellular accumulation of glycogen; in later stages of the disease, glands resembled those of the late secretory phase endometrium. The abnormalities were mirrored by changes in glycan expression. In early disease, there was an increased binding of lectin from Dolichos biflorus agglutinin (DBA) to fucosylated N-acetylglucosamine residues, whereas in later stages, this binding generally decreased in association with the appearance of a late secretory phenotype., Conclusions: Endometriosis is accompanied by progressive changes in the gland architecture and biochemistry resulting in dyssynchrony within the window of uterine receptivity, which may result in the reduced fertility associated with this disease.

This investigation was carried out to study the equine placenta from early gestation to near term, with special reference to morphological changes associated with the development of the vasculature of the fetal component of the microcotyledons. Pregnant uteri were removed post mortem from five Thoroughbred mares between 110 and 309 days of gestation, two of which were aged, multiparous animals suffering age-related degenerative changes in their endometrium (endometrosis), while the other three were young, and had primigravid normal healthy uteri. Pieces of endometrium with placenta attached were fixed for light microscopy and fetal vascular casts were made by injecting the placental arteries with a mixture of Mercox and methylmethacrylate. The casts were examined under the scanning electron microscope. In an aged, endometrotic mare at 110 days of gestation, most of the microplacentomes were irregular in shape with a mean+/-sem diameter of 399+/-30.53 microm. Capillaries with variable diameters made up widely meshed network villi with pointed ends (Type 1 terminal villi), and narrow-meshed networks with finger-like ends (Type 2 terminal villi). In the "paired" young healthy mare at day 121 of gestation, most of the microplacentomes were globular in shape and appeared smaller in diameter than those in the 110-day "pair". The narrow-meshed capillary networks formed villi with stems that consisted of both intermediate and terminal parts, the latter of which represented more the Type 2 than the Type 1 terminal villus. In another aged endometrotic mare at 179 days of gestation, the microplacentomes were typically globular in shape and they showed a mean diameter of 534+/-36.07 microm. The villi were short and thick and they were distinctly differentiated into stem, intermediate and terminal parts. The density of the fetal capillaries had now greatly increased so that, three dimensionally, they constituted bulb-like capillary networks at the base of the stem of each villus. At 199 days in the young healthy "pair", the microplacentomes were again smaller in diameter (402+/-16.24 microm) than in the old mare at 179 days and the interhaemal distance had now reduced to 14.28+/-0.42 microm. The vascular density was lower than in the day 179 aged mare and the fetal villi were much longer and thinner. In the single late stage, healthy young mare at 309 days of gestation (term=336 days), the microplacentomes, each of around 2 mm diameter, exhibited maximal length villi. The capillaries were arranged simply, mostly in straight lines along the axis of the villus, and with communications visible at irregular intervals. Simple and slightly more complicated side capillary loops could be seen along the whole length of the villi and at the top of the terminal villi. Most of the capillaries were characterized by zones containing dilated sinusoids, which increased the surface area for materno-fetal exchange. Thus, the morphological development of the microplacentomes on the surface of the horse placenta during gestation was studied, with special reference to the growth and organisation of the fetal and maternal capillary beds within each microplacentome. The study also reinforced previous work showing the disadvantageous influence of age-related endometrial degenerative changes on microplacentome development and on both the extent and intimacy of physical and haematological contact at the fetomaternal interface, and hence upon fetal growth.

A dog with purulent vulval discharge was found to have many cysts containing purulent mucus in the uterine cervix. The uterine horns did not contain any pus. Histological examination revealed a cervical adenomyosis infiltrated by many neutrophils. After an ovariohysterectomy including the whole cervix, the dog recovered well.

The failure of clearance mechanisms in the mare's uterus results in persistent inflammation and is considered a major cause of subfertility. Eighteen mares, of which three were susceptible to endometritis and four had been ovariectomised, underwent charcoal clearance testing to evaluate their clearance mechanisms. This consisted of installing 500 mg of charcoal (particle size 4 to 90 microm) added to 50 ml of phosphate-buffered saline (PBS) into the uterus. Forty-eight hours later the uterus was flushed out with 0.0012 per cent methylene blue in 50 ml of PBS for determination of the diluting factor by photospectrometry. Flush volume, pH, specific gravity and pellet size were all analysed. To investigate the effect of a beta2-adrenergic agonist on the ability of genitally healthy oestrous mares to eliminate a suspension of charcoal from the uterus, four genitally healthy mares with appropriate charcoal clearance were also subjected to clearance testing following intravenous administration of 0.8 microg/kg of clenbuterol every 12 hours and 1 microg/kg of clenbuterol every eight hours. All parameters were within their normal range following clenbuterol treatment. However, minimal but significant differences in pre- and post-treatment values regarding fluid volume and extinction rate were recorded.

The aim of this study was to investigate the expression of the intermediate filaments cytokeratin, vimentin and desmin in the equine endometrium by immunohistological techniques. For this purpose, endometrial biopsies of 151 mares were examined to determine physiological cycle patterns and changes resulting from endometriosis. During the physiological cycle epithelial cells and mesenchymal cells express cytokeratin and vimentin, respectively, whilst desmin and vimentin were coexpressed by the smooth muscle cells. Epithelial coexpression of cytokeratin and vimentin was seen in numerous fibrotic glands and in the uterine glands of three mares with pathologically inactive endometria. Three different staining patterns (basal, perinuclear, diffuse) of vimentin were associated with typical morphological alterations of the affected epithelia. In addition, in 14 cases a stromal coexpression of vimentin and desmin was found, indicating an atypical stromal differentiation in inactive endometria of older mares, barren for several years.

Pregnancy rates after frozen semen inseminations (AI), particularly in older and problem mares, are lower than after fresh semen AI. Uterine contractility and the inflammatory reaction after frozen semen insemination were studied in two groups of mares: the abnormal group comprised of 6 old barren mares categorized in biopsy category IIB or III, and the control group including 6 reproductively normal young maiden mares in biopsy category I or IIA. All 12 mares were inseminated in the first cycle with 2 mL of phosphate-buffered saline (PBS) and in their second cycle with 2 mL of frozen semen containing 800 x 10(6) spermatozoa. Before and 1, 2, 4, 8, and 20 to 24 h after this treatment, all mares were examined by ultrasonography for intrauterine fluid accumulations (IUFA). The examinations were videotaped to count the number of uterine contractions later. Uterine fluid was obtained by tampon before treatment, and by the tampon method followed by uterine lavage after the last examination. Fluids were cultured bacteriologically, and polymorphonuclear leukocytes (PMN) were counted. Trypsin-inhibitor capacity (TIC), lysozyme concentration, and beta-glucuronidase (BGase) and N-acetyl-beta-D-glucosaminidase (NAGase) activities were determined in frozen-thawed tampon and lavage fluids. Both treatments induced significant neutrophilia in the uterine lumen. Although PMN concentrations were numerically higher after frozen semen AI than after PBS-treatment, the difference was not significant. There was not any difference between the mare groups either. The amount of IUFA differed only in the normal group between frozen semen AI and PBS treatment, and between 0- and 24-h samples for frozen semen AI. Although abnormal mares showed consistently more fluid than normal mares, this difference was not significant. Uterine contractions and enzyme concentrations between groups did not differ. None of the variables showed significant differences between the normal and abnormal mares in their reaction to frozen semen AI.

Objective: To determine the efficacy of anti-tumor necrosis factor therapy (etanercept) for treating endometriosis in baboons., Design: A randomized, placebo-controlled, blinded study using the baboon endometriosis model., Setting: Southwest National Primate Research Center., Animal(s): Twelve female baboons with spontaneous peritoneal endometriosis., Intervention(s): Etanercept (n = 8) or sterile water (n = 4) was administered subcutaneously three times per week., Main Outcome Measure(s): After 8 weeks, the number, color, and surface area of peritoneal lesions was evaluated. Revised American Society for Reproductive Medicine staging was used., Result(s): A statistically significant decrease in red lesion surface area in the treatment group was observed. A trend toward a decrease in the absolute number of red lesions was noted in the treatment group. White and black lesion number and total surface area slightly increased in both groups but failed to achieve statistical significance. Endometriosis was diagnosed in 60% of captive-born baboons with primary infertility., Conclusion(s): These results indicate that etanercept effectively reduces the amount of spontaneously occurring active endometriosis in the baboon.

Background: Endometriosis occurs in several non-human primate species that have menstrual cycles. This study investigated the prevalence and familial aggregation of endometriosis in one of those species, the rhesus macaque., Methods: Between 1978 and 2001, 142 animals with endometriosis were identified from necropsy and surgical records and through the use of magnetic resonance imaging (MRI) at the Wisconsin National Primate Research Center, Madison, USA. All cases were used to build one large multigenerational pedigree and nine nuclear families comprising 1602 females in total. By 2002, the pedigrees contained 124 cases diagnosed at necropsy; 17 at surgery and three at MRI. Female animals that had died aged > or = 10 years without endometriosis, had both ovaries until at least 1 year prior to death, and had a full necropsy, were considered unaffected., Results: The prevalence of endometriosis among necropsied animals aged > or = 10 years in the colony was 31.4% [95% confidence interval (CI) 26.9-35.9%]; prevalence increased with rising age and calendar age at death. Familial aggregation of endometriosis was strongly suggested by a significantly higher average kinship coefficient among affecteds compared with unaffecteds (P < 0.001) and a higher recurrence risk for full sibs (0.75; 95% CI 0.45-1.0) compared with maternal half sibs (0.26; 95% CI 0.10-0.41) and paternal half sibs (0.18; 95% CI 0.02-0.34). The segregation ratio among affected mothers (44.2%) was not significantly higher compared with unaffected mothers (36.6%)., Conclusions: The results support familial aggregation of endometriosis in the rhesus macaque, and indicate that this is a promising animal model for the investigation of mode of inheritance, the location of potential genetic susceptibility loci and the influence of environmental factors.

Chronic degenerative disease of the mare's endometrium is characterised by changes in the uterine glands, including cystic dilation, hyperplasia and periglandular fibrosis. Endometrial biopsies were taken from 23 mares with different grades of endometrial degeneration. Solid structures were identified within the lumina of the uterine glands and shown to be calcified by histochemical staining. Most of them were not homogenous but composed of a mixture of mineral and organic substances. Further examinations of these mineralised structures by immunohistochemical methods revealed the presence of the non-collagenous matrix proteins osteopontin, osteonectin and bone sialoprotein, which are known to be involved in calcification processes such as urolithiosis. Osteopontin and bone sialoprotein were identified within the calculi, frequently arranged in concentric layers. Osteonectin was the only matrix protein that was also present in the glandular epithelium. Osteocalcin was not found in either the calculi or the glandular epithelial cells.

Evaluating the possibility of performing a caesarean section on a cow with dystocia, the economic value of the animal usually plays a central role. The aim of this retrospective study was to analyse and to determine possible factors influencing the fertility. In 1998, 1999 and the first half-year of 2000 a total of 207 cows had a caesarean section. 68% of the inseminated cows which gave birth to a living calf became pregnant again, whereas only 46% of the cows with a dead calf were successfully reinseminated. Thus, 59% of all inseminated cows became pregnant, 2.5% of them had an abortion. The occurrence of retained fetal membranes or of endometritis has been shown to have negative effects on fertility. Only 30% of subsequent inseminations were successful in cows which had suffered from endometritis. The probability of being affected by endometritis was twice as high after birth of a dead calf than after a living calf.

Objective: To use threshold concentrations of acetone and beta-hydroxybutyrate in milk and serum, respectively; identify risk for ketosis and endometritis; and assess analyses of blood and milk samples as predictors of risk for ketosis in high-yielding dairy cows., Animals: 90 multiparous Holstein cows., Procedure: At intervals before and after parturition, blood samples were obtained for determination of glucose, nonesterified fatty acids, leptin, insulin, insulin-like growth factor-1, and beta-hydroxybutyrate concentrations. Samples of milk were obtained at similar intervals after parturition for determination of fat content and concentrations of acetone, protein, and lactose. Reproductive examination of each cow was performed weekly., Results: For each cow, threshold concentrations of acetone and beta-hydroxybutyrate were calculated as 75th and 90th percentiles of maximum postpartum concentrations of acetone in milk (0.40 and 0.87 mmol/L) and beta-hydroxybutyrate in serum (2.30 and 3.51 mmol/L). Significant decrease in milk production (442 to 654 kg of energy-corrected milk/305-day period per cow) was associated with acetone or beta-hydroxybutyrate in excess of threshold values. Milk acetone concentrations > 0.40 mmol/L were associated with 3.2 times higher risk for endometritis. Low plasma glucose, high serum beta-hydroxybutyrate, and high milk acetone concentrations during week 1 after parturition were indicators of increased risk for ketosis later during lactation., Conclusions and Clinical Relevance: Determination of milk acetone concentration during the week after parturition may identify cows at risk for ketosis and endometritis; with appropriate interventions, development of disease and production losses may be reduced.

Spontaneous endometriosis was diagnosed in 43 baboons over a 14-year period. Thirty-seven have died; five remain alive; one was sold and lost to follow-up. The average age at diagnosis was 17.2 years; 29 (67%) were between 12 and 21 years of age. Fifteen (35%) were diagnosed by biopsy and received surgical excision of the endometriotic tissue; four of these were identified during caesarian section, confirming one prior report of endometriosis in pregnant animals. Twenty-eight (65%) were diagnosed at or shortly preceding necropsy. When diagnosed by a palpable abdominal mass, there was a significantly greater likelihood the animal died or was killed as a result of complications of endometriosis. When diagnosis was at necropsy, there was a significantly greater likelihood that the animal died from causes unrelated to endometriosis. Early identification with surgical removal appears to provide a benefit for both survival and delivering offspring after diagnosis. In twenty-one baboons (49%), endometriosis affected multiple sites within the peritoneal cavity. In the remaining baboons, lesions were more localized. Ovarian involvement was seen in sixteen (37%) of these baboons. This paper is the first to describe significant ovarian involvement in baboons, previously considered a limitation of the usefulness of this species as an animal model. We also describe the first reported endometriosis seeding of an abdominal surgery scar in a baboon. Many of these baboons were middle aged, had few or no offspring, or had evidence of a long duration of uninterrupted menstrual cycles, consistent with risk factors for women. Endometriosis was an incidental finding in 17 (40%) of these baboons, consistent with previous reports of minimal endometriosis as a common asymptomatic finding in baboons and in women. Overall, endometriosis in baboons presents a spontaneously occurring animal model that shares important features with the disease in women and the rhesus macaque.

The purpose of this study was to evaluate the effects of estrogen and progesterone on the vaginal mucosa and their role in vaginal transmission of simian immunodeficiency virus. Incidentally, endometrial hyperplasia was observed in estrogen-treated monkeys at necropsy. Six adult female rhesus monkeys (Macaca mulatta) were ovariectomized and 120 days later received two subcutaneous implants, each containing 200 mg estradiol. The animals were sacrificed 17-27 months later and the uterus examined at necropsy. All the monkeys had simple endometrial hyperplasia, some with polyps or adenomyosis, at the time of necropsy. The severity of the changes correlated with the time between implantation and necropsy. The lesions were similar to endometrial hyperplasia caused by unopposed estrogen in women, but occurred over a time period that is suitable for experimental manipulation. Rhesus monkeys could be used as a model to test the safety of various combinations of sex steroids for the prevention of postmenopausal symptoms in women.

During exploratory laparotomy, a 10-year-old female rhesus macaque was found to have a 6.0 x 9.5 x 2.0-cm multichambered, yellow, cystic mass cranial to the uterus, from which large amounts of opaque, white fluid were discharged into the abdominal cavity. The animal was euthanized, and the body was submitted for gross and histologic evaluation. Sections of the mass examined microscopically consisted of sheets of polygonal to round cells, with well defined cell borders and moderate amounts of eosinophilic cytoplasm. Scattered throughout these cells were few, variably sized glandular structures composed of columnar to cuboidal epithelium. Glandular epithelial cells were positive for keratin, and the sheets of polygonal cells were positive for vimentin and negative for keratin and CD 68. Gross and histologic appearance, immunohistochemical findings, and history of medroxyprogesterone acetate injections were compatible with a diagnosis of stromal decidualization of endometriosis. Subsequent biopsies of similar lesions in other rhesus macaques in the colony being treated with medroxyprogesterone acetate for endometriosis revealed comparable histologic findings.

A focal uterine adenomyosis is described in two bitches. In both cases, the uterus showed knobbly enlargements of 4 to 8 cm in diameter, which resulted in distinct clinical symptoms. Other pathological changes of the uterus were not present. One bitch was presented because of a history of vaginal discharge of several months' duration. Radiographs, as well as ultrasonography, revealed a soft tissue lesion at the cervix. The other bitch showed a marked reduction in its general condition and a sudden onset of a tense abdomen. Radiologically, a lesion of soft tissue opacity was observed in the mid-abdomen and was seen to originate from the left uterine horn during exploratory laparotomy. A torsion of the lesion was present, which explained the clinical signs in this second case.

Periglandular fibrosis and cystic dilation of uterine glands are associated with equine endometriosis. The presence of extracellular matrix proteins (collagen type I, III and IV, laminin and fibronectin) in healthy and endometriotic specimens was demonstrated by immunohistochemistry. The distribution of collagen I, but not collagen III, was dependent on the stage of the oestrous cycle. The arrangement of collagen I and collagen III in endometriotic specimens was similar to that in normal endometrium. In periglandular fibrosis, collagen IV, laminin and fibronectin deposition outside the basement membrane was observed. In these regions, stromal cells were characterized immunohistochemically as myofibroblasts because of their expression of a-smooth muscle actin, and occasionally tropomyosin and desmin. Periglandular differentiation of contractile cells could be interpreted as a reaction to support the extrusion of secretions in cystic dilated glands. Moreover, the changes of extracellular matrix proteins are characteristic for neoplastic lesions, although further development of endometriosis to benign or malignant tumours is not known in horses. Knowledge of the factors responsible for these fibroblastic modulations may be the key to explaining the pathogenesis of endometriosis.

One of the major progesterone-dependent endometrial proteins in the mare is a novel 19 kDa lipocalin (P19). This protein is secreted by the endometrial glands and is readily detectable in uterine secretions during the luteal phase of the oestrous cycle and early pregnancy. The function of P19 is unknown, but since most lipocalins act as carriers of small hydrophobic molecules, it probably transports a maternal factor to the conceptus during pregnancy. In this study, a high titre antiserum raised against recombinant-derived P19 was used to detect by immunohistochemistry the protein in endometrial biopsies from normal healthy mares and mares with endometrosis. Immunoreactive P19 was undetectable in prepubertal fillies and in anoestrous mares and was barely detectable in oestrous mares. However, it was present in large amounts during dioestrus and very early pregnancy, and in moderate amounts after day 20 of gestation. In six subfertile mares with endometrosis, an abnormal pattern was found at all stages of the reproductive cycle, especially in the 'gland nests'. These showed either an absence of P19 or an accumulation of the protein due to a lack of secretion, thus indicating asynchronous glandular activity. These results identified a high proportion of abnormal, asynchronous endometrial glands in a group of subfertile mares and indicated that abnormal secretion of P19 may be one of the reasons for the reduced fertility rates observed in aged mares with endometrosis.

We describe endometriosis in an aged rhesus macaque. There was a large mass and a related paraovarian cyst, typical of the disease. Endometriosis is a common finding in nonhuman primate. In this report, we also review the pathophysiology of the disease and summarize the historical and more recent relevant literature. Given the frequency of endometriosis in the rhesus monkey and the long-life spans (15-30 years) of nonhuman primates in captivity, endometriosis should be suspected in animals displaying the earliest signs of the disease: anorexia, dysmenorrhea, menorrhagia, irregular menstrual cycles, or infertility. Despite recent advances in the diagnosis and therapeutic strategies for endometriosis in women, the disease remains a significant cause of morbidity and ultimately, a cause of mortality, in the older nonhuman primate.