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The diagnosis rate of chronic endometritis (CE), closely associated with infertility, recurrent pregnancy loss, and recurrent implantation failure, remains low in clinical practice. The monocyte percentage (MP) has been identified as a biomarker predicting prognosis in various severe diseases. Although monocytes have been linked to clinical endometritis in animals, their associations with CE in infertile patients remains unclear. This cross-sectional study included patients pathologically diagnosed with CE at a single center in 2021. Demographic data, history of abortion, causes of infertility, Ureaplasma urealyticum infection history, laboratory findings, and histological information were recorded. The correlation between MP and CE was investigated using logistic regression analysis, and subgroup analyses were conducted based on age, gravidity, parity, and follicular phase. The cohort consisted of 631 individuals, including 494 patients with CE, corresponding to a CE prevalence of 78%. Univariate logistic regression analysis revealed an inverse correlation between MP and CE risk (odds ratio [OR] = 0.85; 95% confidence interval [CL], 0.76–0.96; P  < 0.01). Multivariate regression after adjusting for all covariates yielded an OR of 0.82 (95% CI 0.71–0.95). Furthermore, the stratified and subgroup analyses yielded consistent results. Sensitivity analyses excluding participants with pathological endometrial changes (OR = 0.83; 95% CI 0.71–0.96), those in the non-follicular phase (OR = 0.78; 95% CI 0.66–0.92), and those with both endometrial abnormality and non-follicular phase status (OR = 0.82; 95% CI 0.7–0.95) further confirmed the correlation between MP and CE risk. MP was significantly associated with CE in infertile participants in models adjusted for all covariates, suggesting that MP may be a valuable parameter for early CE prediction.

This study investigated differences in uterine and serum metabolome associated with clinical cure failure of metritis in dairy cows. Metritis was diagnosed in lactating Holstein cows from two Florida dairies and defined by the presence of fetid, watery, reddish-brown vaginal discharge from 4 to 12 days postpartum (dpp). Cows with metritis (n = 24) were paired with cows without metritis of similar parity and dpp (n = 24). On the day of metritis diagnosis (day 0), all cows with metritis received antimicrobial therapy. The continued presence of the fetid, watery, reddish-brown discharge on day 5 (n = 16) was defined as clinical cure failure, whereas clinical cure was defined by its absence (n = 8). Metabolome analyses of uterine lavage (days 0 and 5) and serum samples (day 0) were conducted using untargeted gas chromatography time-of-flight mass spectrometry. Normalized data were analyzed using partial least squares–discriminant analysis and ANOVA, adjusting P-values for multiple comparisons. Differences in the uterine metabolome on day 0 associated with clinical cure failure were linked to carbohydrate, amino acid, and lipid metabolism. Greater concentrations of arachidonic acid, ribose, and glutaric acid were associated with clinical cure failure, suggesting a greater degree of tissue lesion and inflammation. No differences in the serum metabolome were associated with cure failure. No differences in uterine metabolome were associated with clinical cure failure on day 5. The findings suggest that clinical cure failure is associated with a greater uterine inflammatory process that did not persist until cure assessment day. Summary Sentence Clinical cure failure in dairy cows with metritis is linked to distinct uterine metabolome profiles, inflammatory processes, and energy metabolism present on the day of metritis diagnosis but not on cure assessment day. Graphical Abstract

PurposeThe current gold standard for chronic endometritis (CE) diagnosis is immunohistochemistry (IHC) for CD-138. However, IHC for CD-138 is not exempt from diagnostic limitations. The aim of our study was to evaluate the reliability and accuracy of MUM-1 IHC, as compared with CD-138.MethodsThis is a multi-centre, retrospective, observational study, which included three tertiary hysteroscopic centres in university teaching hospitals. One hundred ninety-three consecutive women of reproductive age were referred to our hysteroscopy services due to infertility, recurrent miscarriage, abnormal uterine bleeding, endometrial polyps or myomas. All women underwent hysteroscopy plus endometrial biopsy. Endometrial samples were analysed through histology, CD138 and MUM-1 IHC. The primary outcome was to evaluate the diagnostic accuracy of MUM-1 IHC for CE, as compared with CD-138 IHC.ResultsSensitivity and specificity of CD-138 and MUM-1 IHC were respectively 89.13%, 79.59% versus 93.48% and 85.03%. The overall diagnostic accuracy of MUM-1 and CD-138 IHC were similar (AUC = 0.893 vs AUC = 0.844). The intercorrelation coefficient for single measurements was high between the two techniques (ICC = 0.831, 0.761–0.881 95%CI). However, among CE positive women, MUM-1 allowed the identification of higher number of plasma cells/hpf than CD-138 (6.50 [SD 4.80] vs 5.05 [SD 3.37]; p = 0.017). Additionally, MUM-1 showed a higher inter-observer agreement as compared to CD-138.ConclusionIHC for MUM-1 and CD-138 showed a similar accuracy for detecting endometrial stromal plasma cells. Notably, MUM-1 showed higher reliability in the paired comparison of the individual samples than CD-138. Thus, MUM-1 may represent a novel, promising add-on technique for the diagnosis of CE.

Cattle with subclinical endometritis (SCE) are sub-fertile and diagnosing subclinical uterine disease remains a challenge. The hypothesis for this study was that endometrial inflammation is reflected in mRNA expression patterns of peripheral blood leucocytes. Transcriptome profiles were evaluated in healthy cows and in cows with SCE using circulating white blood cells (WBC) and endometrial biopsy samples collected from the same animals at 45–55 days postpartum. Bioinformatic analyses of microarray-based transcriptional data identified gene profiles associated with distinct biological functions in circulating WBC and endometrium. In circulating WBC, SCE promotes a pro-inflammatory environment, whereas functions related to tissue remodeling are also affected in the endometrium. Nineteen differentially expressed genes associated with SCE were common to both circulating WBC and the endometrium. Among these genes, transcript abundance of immune factors C3, C2, LTF, PF4 and TRAPPC13 were up-regulated in SCE cows at 45–55 days postpartum. Moreover, mRNA expression of C3, CXCL8, LTF, TLR2 and TRAPPC13 was temporally regulated during the postpartum period in circulating WBC of healthy cows compared with SCE cows. This observation might indicate an advantageous modulation of the immune system in healthy animals. The transcript abundance of these genes represents a potential source of indicators for postpartum uterine health

This study aimed to evaluate the relationship between prepartum subclinical hypomagnesemia (pre-SHMg) and the occurrence of dystocia, metritis, clinical mastitis, lameness, and subclinical hypomagnesemia postpartum (post-SHMg) in pasture-based dairy cows. Also, the difference in means of prepartum magnesium (Mg) concentration by postpartum health events was evaluated. A total of 890 dairy cows from 32 commercial farms located in southern Chile were enrolled. Cows were examined twice, once between 30 and 3 days before and once between 3 and 30 days after calving. Blood samples were collected on both assessments, and cows were considered as having SHMg if serum total Mg < 0.65 mmol/L. On the postpartum visit, cows were evaluated for metritis and lameness. Information about clinical mastitis and dystocia was collected from on-farm records. Data were analyzed using multivariable mixed linear models and multivariable mixed logistic regression models. The overall prevalence of pre-SHMg was 9.9%, and its presence was associated with the occurrence of post-SHMg (odd ratio [OR] = 5.7; P < 0.0001) and metritis (OR = 3.1; P = 0.04). However, we did not detect an association between pre-SHMg and dystocia, clinical mastitis, or lameness after calving. Prepartum serum Mg concentrations were lower in cows that developed post-SHMg than those that did not (LSM ± SE = 0.75 ± 0.02 mmol/L vs. 0.83 ± 0.02 mmol/L; P < 0.0001). In conclusion, pre-SHMg was associated with a higher risk of post-SHMg and metritis in grazing dairy cows but not other postpartum health events.

The aim of the study was to evaluate the concentrations of proinflammatory cytokines: tumor necrosis factor (TNF-α) and interleukin-6 (IL-6), anti-inflammatory cytokine interleukin-10 (IL-10), and acute phase proteins (APPs)—haptoglobin (Hp) and serum amyloid A (SAA) in serum and uterine washings of cows with subclinical endometritis, and compare them to healthy animals. The study was performed on 24 cows on day 60 after delivery. The cows were divided into two groups based on the results of cytological tests: 12 cows with subclinical endometritis and 12 healthy cows. Experimental material consisted of blood serum and uterine washings. The levels of the following cytokines in the study material were determined with ELISA: TNF-α, IL-6, IL-10 and APPs - Hp and SAA. The results show that the levels of TNF-α ( p  < 0.01), IL-6, IL-10 as well as SAA and Hp were significantly higher in the serum of cows with subclinical endometritis compared to the controls ( p  < 0.001). Uterine washings had significantly higher levels of IL-6, IL-10, and Hp in the experimental cows compared to the controls ( p  < 0.001). The demonstrated differences in the concentration of cytokines and APP between cows with subclinical endometritis and healthy cows, in both the serum and uterine washings, may suggest the usefulness of these parameters in the diagnosis of subclinical endometritis in cows in the late postpartum period.

Endometritis is an inflammatory disorder of the endometrial lining of the uterine tissue in postpartum stage. Endometritis mostly progresses subclinically and causes infertility through the disruption of the hormonal balance. It has been shown in many studies that resveratrol has anti-inflammatory and antioxidant properties. However, the possible beneficial effects of resveratrol in endometritis have not been determined yet. The aim of the present study is to evaluate the treatment potential of resveratrol in an experimentally induced endometritis model in rats. Endometritis was induced in 12-week-old female, nonpregnant, Sprague Dawley rats. The animals were divided into six groups: control (NaCl 0.9%) and endometritis (NaCl 0.9%), marbofloxacin + PGF2α, marbofloxacin, marbofloxacin + resveratrol, and resveratrol groups. To induce endometritis, 5 mg/kg/s.c. progesterone was given for 5 days, and then Escherichia coli (50 μl, 1 × 105 cfu/rat) was injected in the right cornu uteri following laparotomy. Sixteen hours after bacterial inoculation, the treatment protocol was applied for 14 days. At the end of the experiment, the total oxidant status (TOS) and total antioxidant status (TAS) were examined spectrophotometrically in uterus tissues. The severity of inflammation in uterus samples and follicular activity in ovarian tissues were histopathologically evaluated. In addition, serum cytokine levels were determined. While TAS in uterine tissue significantly increased in the resveratrol group when compared to that of the other groups (p < 0.05), there was no difference between the groups in TOS (p > 0.05). The inflammation of the endometrium and the numbers of corpus luteum in the endometritis group were highly significant when compared to those of the other groups (p < 0.05). The recovery of inflammation and follicular activity were similar to those of the other groups in resveratrol group. However, it was realized that resveratrol administration reduced serum cytokine levels. According to the results of the current study, resveratrol was found to be effective in the treatment of endometritis with its antioxidant and anti-inflammatory functions.

Background Endometritis is a common problem in a broodmare practice, often leading to infertility. The diagnosis is based on several methods such as cytology, bacteriology and histopathology; however the outcome of these methods may be inconclusive even when used together. The objectives of this study were: (1) to investigate the usefulness of acute phase proteins as an additional diagnostic tool for diagnosis of subclinical endometritis in mares and (2) to evaluate the association between macroscopic changes in uterine flushes and inflammation of the uterus. Materials were collected from 53 Icelandic mares with subclinical endometritis. Endometrial swabs and uterine lavage for cytological and bacteriological examinations and two endometrial biopsies were taken. Blood samples were collected 12–24 h after ovulation to determine the concentrations of serum amyloid A and haptoglobin in the 53 subfertile mares and, for comparison, from 20 non-pregnant mares that later conceived. Results Twenty-five mares were classified as positive for endometritis based on endometrial biopsy, which was used as the ‘gold standard’. We observed a correlation between cloudy efflux in the lavage and (1) polymorphonuclear cell (PMN) infiltration of the endometrium ( P  = 0.031), (2) positive cytology in samples obtained by cotton swabs ( P  = 0.019) and uterine lavage ( P  = 0.011), and (3) positive microbiology from samples obtained by cotton swabs ( P  = 0.001) and uterine lavage ( P  = 0.047). The degree of agreement between PMN infiltration and positive cytology from samples taken by cotton swabs and uterine lavage was fair to moderate. We found no association between the concentration of acute phase proteins and infiltration of the endometrium by PMNs, or with positive results of cytological and microbiological examinations. Conclusions Measurement of serum amyloid A and haptoglobin was not proven useful for diagnosis of subclinical endometritis in Icelandic mares. Macroscopic changes in the fluid collected by lavage were not consistently indicative of infection, but when present they indicate inflammation in the uterus with a high probability.

This study was undertaken to elucidate the adverse effect of lead on female reproductive system following in vivo exposure in rats. Animals of Group II, III and IV received lead acetate in drinking water (30, 100 and 300 ppm, respectively) for 28 days whereas Group I served as control. Lead levels in digested blood and bone samples were measured using atomic absorption spectrophotometer. Marked and a significant decrease in per cent body weight gain was observed in rats of Group IV and III, respectively, compared to that in the control group. Relative uterine weights were found to decrease by 27% in Group III and IV compared to control and low dose lead treated (30 ppm) rats. Lead levels were found to increase in a linear manner in blood along with a marked increase in bone levels in 100 ppm exposure group while there was a decrease in both the blood and bones levels at 300 ppm exposure. Compared to plasma progesterone levels in rats of the control group, a nonsignificant (12.46-21.13%) reduction in plasma progesterone were observed in different lead-treated groups. No apparent gross pathological lesions were observed in any of the vital organs, including uterus. However, histopathological examination of uteri of different groups revealed lead-induced dose-dependent inflammatory changes, which were characterized by thickening of the endometrium, narrowing of uterine lumen, damage to endometrial glands and vacuolar degeneration in endometrial epithelial cells. Findings of this study suggest lead-induced pathophysiological alterations in myometrium, which in turn may affect the reproductive efficiency of animals.

Background Postpartum endometritis in cattle is a multifactorial disease with high economic impact. Both, clinical endometritis (CE) and subclinical endometritis (SCE) result in decreased reproductive performance. Results from in vitro studies led to the implication that non-esterified fatty acids (NEFA), beta-hydroxybutyric acid (BHBA), bilirubin, and urea could be used as predictors for endometritis in veterinary practice. In this field study, we set out to establish optimal predictor cut points of these metabolic parameters for the detection of CE and SCE. Serum samples were collected one week prior to parturition (wk -1), in the first week postpartum (wk +1) and between 28 and 35 days postpartum (wk +5) from 209 Holstein-Friesian cows. At wk +5, all cows were examined for signs of CE and SCE. Results Higher concentrations of urea at wk +1 were associated with increased odds of CE (OR = 1.7, P = 0.04) in primiparous (PP) cows. A predictor cut point of 3.9 mmol/L (sensitivity: 61%, specificity: 70%) was determined. In multiparous (MP) cows, the logistic regression model revealed that higher concentrations of NEFA at wk -1 were associated with increased odds of CE and SCE (healthy vs. CE: OR = 9.1, P = 0.05; healthy vs. SCE: OR = 12.1, P = 0.04). A predictor cut point of 0.3 mmol/L (sensitivity: 38%, specificity: 87% and sensitivity: 35%, specificity: 89%, respectively) was determined. Increasing concentrations of urea at wk +5 were associated with decreased odds of CE (healthy vs. CE: OR = 0.6, P = 0.01; SCE vs. CE: OR = 0.5, P = 0.03). A predictor cut point of 3.8 mmol/L (sensitivity: 52%, specificity: 81%) was determined. For BHBA and bilirubin relationships with CE or SCE were not detected. Conclusions The corresponding combinations of sensitivity and specificity of the determined predictor cut points were not satisfactory for practical use. Thus, the analysed parameters, i.e. NEFA, BHBA, bilirubin, and urea, at the chosen time points, i.e. at wk -1, at wk +1, and at wk +5 relative to calving, are unsatisfactory for disease prediction. Further research is required to clarify the questions raised by the current study.