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Purpose: To evaluate the proposed criteria in a large sample and in additional subgroups in order to test the validity of the hysteroscopic features widely-accepted as suggestive of CE., Method(s): All patients (n: 2675) underwent outpatient hysteroscopy, with the vaginoscopic approach technique. Hysteroscopic features such as, stromal oedema, diffuse or focal hyperaemia, "strawberry aspect", micropolyposis and endometrial polyps, are often indicate the presence of chronic endometritis. All hysteroscopic features, alone and in combination were applied in 7 (seven) different subgroups of the sample: total sample, women in reproductive age, women with infertility issues/IVF screening, women with history of recurrent miscarriages, menopausal women, and women with hysteroscopic indication of Abnormal Uterine Bleeding (AUB) in women of reproductive age and postmenopausal bleeding (PMB). From each case, endometrial samples were obtained and immunohistochemistry, identifying CD-138, was applied in order to diagnose CE., Result(s): A total of 2675 patients were included of which, 1444 women were found with at least one of the proposed hysteroscopic features mentioned above. Stromal oedema, focal or diffuse hyperaemia and "strawberry aspect" in combination with micropolyposis demonstrated higher rates of diagnostic accuracy in the detection of CE correlated to histologic confirmation. Micropolyposis, stromal oedema, focal or diffuse hyperaemia and "strawberry aspect" offer great diagnostic accuracy in the hysteroscopic detection of Chronic Endometritis, regardless reproductive status and/or clinical presentation. Endometrial polyps are not valid hysteroscopic features in cases of suspected CE., Conclusion(s): Diagnostic hysteroscopy can accurately diagnose cases of CE, based on stromal oedema, focal or diffuse hyperaemia and "strawberry aspect", in combination with micropolyposis. In subgroups of infertile women, higher diagnostic accuracy based on the hysteroscopic features mentioned, was more likely to be achieved. Whether endometrial polyps are suggestive of CE, when identified during office hysteroscopy, remains controversial., Competing Interests: Declaration of Competing Interest All authors declare no conflict of Interest., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background: The purpose of the present study was to evaluate the relationship between chronic endometritis and the epithelial-mesenchymal transition in the endometrium of infertile patients in the implantation phase., Methods: Endometrial biopsy specimens from 66 infertility patients were analyzed. The presence of chronic endometritis was investigated by immunostaining for CD138. Immunohistochemical staining for E-cadherin, N-cadherin, Slug, and Snail was performed, and the expression profiles were statistically analyzed according to the presence of chronic endometritis. When the loss of E-cadherin expression and/or the positive expression of N-cadherin was detected, the specimen was considered epithelial-mesenchymal transition-positive. Epithelial-mesenchymal transition-positive cases were also statistically analyzed according to the presence of chronic endometritis. The characteristics of the patients in the epithelial-mesenchymal transition-positive and epithelial-mesenchymal transition-negative groups were compared. The association between variables, including age, body mass index, gravidity, parity, and each causative factor of infertility and epithelial-mesenchymal transition positivity was analyzed., Results: The rates of the loss of E-cadherin expression, the gain of N-cadherin and epithelial-mesenchymal transition positivity were significantly higher in chronic endometritis patients. The expression of Slug, cytoplasmic Snail, and nuclear Snail was also detected at significantly higher rates in chronic endometritis patients. Chronic endometritis were related to the epithelial-mesenchymal transition., Conclusion: The epithelial-mesenchymal transition was frequently detected in the endometrium in infertile patients with chronic endometritis. Since the epithelial-mesenchymal transition is associated with chronic endometritis, the epithelial-mesenchymal transition appears to be involved in the alteration of mechanisms of implantation., Competing Interests: The authors have declared that no competing interests exist.

Chronic inflammatory processes affecting the endometrium, as encountered in endometriosis, adenomyosis, and chronic endometritis, alter endometrial receptivity. These disorders are associated with early pregnancy losses and possibly recurrent pregnancy losses (RPL). In the cases of endometriosis, other factors associated with the disease also are susceptible of causing miscarriages and possibly RPL, such as an impact of intrapelvic inflammatory processes affecting the oocyte and embryo in case of natural conception. Conversely these latter effects obviously are bypassed in case of assisted reproductive technology. Chronic inflammation of the endometrium in the condition known as chronic endometritis also causes early pregnancy losses and RPL with beneficial effects achieved when specific treatment is undertaken., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Our objectives were to compare the effects of ceftiofur crystalline free acid (CCFA) and ampicillin trihydrate (AMP) treatments of cows diagnosed with metritis on uterine health, behavior, reproductive, and productive responses. A controlled randomized clinical trial was designed. Metritis was defined as vaginal discharge (VD) = 5 (fetid, watery, red/brown) within 21 d in milk (DIM) and rectal temperature (RT) <39.5°C, whereas VD = 5 and RT ≥39.5°C was defined as puerperal metritis. On the day of diagnosis (d 0), cows were paired by parity and severity of metritis (metritis vs. puerperal metritis) and assigned randomly to the AMP and CCFA treatments. Cows enrolled in the AMP (n = 308) treatment were moved to a nonsalable-milk pen, where they were treated once daily for 5 d, and were moved back to their original pen 72 h after the last treatment (d 7). Cows enrolled in the CCFA (n = 310) treatment remained in their original pen and received 2 treatments of CCFA, 72 h apart. Rectal temperature was measured daily from d 0 to 6 and on d 11. Vaginal discharge was evaluated on d 4, 6, and 11 to assess cure. Cure was defined as the absence of treatment with additional antimicrobial before experiment d 11, VD <5, and RT <39.5°C. Cows were examined at 28 ± 3 DIM for purulent VD (PVD) and at 35 ± 3 DIM for cytological endometritis. Pregnancy was diagnosed at 40 ± 3 and 60 ± 7 d after first and second artificial inseminations. Cure of metritis did not differ between treatments on d 11 (AMP = 64.6 ± 3.1, CCFA = 63.5 ± 3.1%). Cows treated with AMP had greater RT from experiment d 1 to 6 compared with cows treated with CCFA (AMP = 39.1 ± 0.02, CCFA = 39.0 ± 0.02°C). Cows in the AMP treatment had greater prevalence of PVD at 28 ± 3 DIM (AMP = 82.6 ± 2.3, CCFA = 74.4 ± 2.7%) and tended to have greater prevalence of cytological endometritis at 35 ± 3 DIM (AMP = 77.8 ± 6.2 vs. CCFA = 61.7 ± 7.5%) than CCFA-treated cows. Treatment did not affect the hazard of pregnancy among multiparous cows; however, among primiparous cows, CCFA treatment reduced the hazard of pregnancy and increased the median days to pregnancy (AMP = 145 vs. CCFA = 169 d). Finally, average daily milk yield up to 14 wk postpartum was not affected by treatment (AMP = 38.0 ± 0.4, CCFA = 37.5 ± 0.4 kg). We conclude from the current experiment that CCFA was more effective in reducing RT and improving uterine health of metritic cows; however, the improved hazard of pregnancy of primiparous cows treated with AMP is important and warrants further investigation., (Copyright © 2021 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

In postpartum buffaloes, the process of uterine involution and changes in blood metabolic profile has not been studied in relation to development of subclinical endometritis (SCE). In this study, buffaloes (n = 100) approaching calving were identified. Weekly blood samples were collected on the day of calving up to 6 weeks post-calving. The diameter of uterine horns and onset of ovarian cyclicity (corpus luteum) were recorded through ultrasonography. On the basis of polymorphonuclear cell (PMN) cell count in endometrial cytology at days 45-50 postpartum, buffaloes were divided into two groups, viz., with SCE (> 5% PMN; n = 38) and without SCE (≤ 5% PMN; n = 62). Buffaloes with SCE took longer (P < 0.05) time to complete uterine involution and had larger (P < 0.05) uterine horn diameter between 3rd and 6th weeks postpartum and lower prostaglandin F2α metabolite (PGFM) concentration on the day of calving (P < 0.05) and 1 week (P < 0.001) post-calving than without SCE group. Buffaloes with SCE had lower (P < 0.001) concentration of glucose at weeks 2 and 3, higher (P < 0.001) β-hydroxybutyric acid (BHBA) at week 3, and lower serum albumin concentration throughout the sampling period (P < 0.05 to 0.001) except at 1 week post-calving as compared to without SCE group. The urea concentration was significantly lower (P < 0.05 to 0.001) in buffaloes with SCE from 4 weeks post-calving onwards than without SCE group. The calcium concentration was lower in buffaloes with SCE at weeks 5 (P < 0.001) and 6 (P < 0.05) postpartum, whereas the concentration of magnesium and phosphorus was uniform between the two groups. No significant (P > 0.05) difference in onset of ovarian cyclicity between the 2 groups was observed, whereas buffaloes with SCE had longer (P = 0.001) median days open (141 days) than their counterpart (117 days). The first service conception rate, cumulative pregnancy rate, and pregnancy rate at 150 days postpartum were lower (P < 0.05) in buffaloes with SCE than without SCE group. In summary, higher BHBA and lower serum concentrations of glucose, albumin, urea, and calcium control onset of subclinical endometritis which in turn has negative impact on fertility of buffaloes.

Purpose: Chronic endometritis (CE) is a frequent hysteroscopic and histological finding which affects embryo transfer implantation during IVF-ICSI cycles. In particular, CE impairs proper decidualization and, subsequently, implantation. Although this correlation has been clearly clarified, a pathophysiological explanation assembling all the studies performed has not been elucidated yet. For this reason, we have structured a systematic review considering all the original articles that evaluated a pathological element involved in CE and implantation impairment., Methods: The authors searched electronic databases and, after screening, collected 15 original articles. These were fully scanned and used to create a summary pathway., Results: CE is primarily caused by infections, which lead to a specific cytokine and leukocyte pattern in order to prepare the uterus to fight the noxa. In particular, the immunosuppression requested for a proper semi-allogenic embryo transfer implantation is converted into an immunoreaction, which hampers correct embryo implantation. Moreover, endometrial vascularization is affected and both irregular vessel density and luminal thickening and thrombosis reduce what we have first identified as endometrial flow reserve. Finally, incorrect uterine wave propagation could affect embryo contact with decidua., Conclusion: This is the first summary of evidence on CE pathophysiology and its relationship with infertility. Understanding the CE pathophysiology could improve our knowledge in embryo transfer success.

Infertility is a common consequence of cows suffering from postpartum uterine diseases. Diseases from a uterine origin in early lactation affect both uterine and ovarian tissues decreasing the probability of pregnancy. The objective of the present study was to determine the impact of clinical metritis, clinical endometritis, and subclinical endometritis on days open in cows from high-altitude tropical dairy herds. A single cohort longitudinal study was conducted from January 2018 to February 2019, which included 248 cows enrolled from five commercial high-altitude tropical dairy herds in the northern region of the Department of Antioquia, Colombia. A directed acyclic graph was used to identify minimal sufficient adjustment sets for each exposure variable of interest. Based on the directed acyclic graph, three models (one for each of clinical metritis, clinical endometritis, and subclinical endometritis) were proposed to assess the impact of postpartum uterine diseases on days open. The time at risk was defined as the days elapsed from calving until pregnancy (event or censure). Observations were right-censored if cows were either culled, dead, were lost to follow up, suffered a systemic illness that required the use of parenteral drugs, or if they were not pregnant at 210 postpartum days. Three Cox proportional hazards models were proposed to estimate the Hazard Ratios (HR) at any point in the follow-up period for each exposure variable. The hazard of pregnancy was significantly lower for cows with metritis (40 %; HR = 0.60; 95 % CI: 0.43 - 0.86), clinical endometritis (69 %; HR = 0.31; 95 % CI: 0.22 - 0.45), and subclinical endometritis (76 %; HR = 0.24; 95 % CI: 0.16 - 0.36) compared to their herd mates without these conditions. These results provide evidence of the negative impact of postpartum uterine diseases on time to pregnancy in grazing lactating dairy cows from high-altitude tropical herds., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Research Question: What is the prevalence of disrupted markers of endometrial function among women experiencing recurrent implantation failure (RIF), and does the prevalence differ from a control cohort?, Design: Prospective controlled cohort study. In total, 86 women with a history of RIF and 37 women starting their first fertility treatment were recruited for this study. Endometrial and blood profiling were carried out in a hormone-substituted cycle using oestradiol and progesterone. Endometrial biopsies were analysed by histology, immune cell profiling, and the endometrial receptivity array (ERA®) test (Igenomix, Valencia, Spain). The vaginal microbiome was analysed using a NGS-based technology (ArtPRED, Amsterdam, the Netherlands). Blood tests included oestradiol, progesterone, prolactin, thyroid-stimulating hormone, vitamin D and anti-phospholipid antibody levels., Results: Patients who had experienced RIF produced a range of test abnormalities. Compared with controls, women with RIF had a higher prevalence of chronic endometritis (24% versus 6%), a lower vitamin D level and a borderline lower progesterone level. Women who had experienced RIF had a more favourable vaginal microbiome compared with controls. Although the RIF cohort was older than the controls (mean age 33.8 years versus 30.2 years), no differences between the groups were observed in immune cell profiling and the ERA test., Conclusion: These data demonstrate that a single test or treatment for the endometrial factor in RIF is unlikely to be clinically effective. Diagnosing the endometrium in women with RIF permits targeted rather than blind interventions. Relative vitamin D deficiency, lower mid-luteal progesterone and chronic endometritis are ready targets for treatment. Understanding the role and treatment of an unfavourable vaginal microbiome in RIF needs further investigation., (Copyright © 2020 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

The first aim of this study was to evaluate the relationship between the concentrations of plasma insulin-like growth factor-I (IGF-I) in the transition period and the incidence of clinical endometritis postpartum. The second aim was to evaluate the relationship between the concentration of plasma IGF-I in the transition period and the estrous synchrony response and pregnancy rate to a controlled internal drug release (CIDR) protocol. A total of 402 dairy cows, 250 multiparous and 152 primiparous, were enrolled. A blood sample was taken from all cows 2 and 1 wk precalving and wk 1, 3, 4, and 5 postcalving for subsequent analysis of IGF-I. Vaginal discharge score as a measurement of uterine health was recorded in wk 3, 4, and 5 postcalving. Estrous cycles of all cows were synchronized on ≥37 d in milk (mean = 59; range 37-93) using an 8-d CIDR protocol. All cows were scanned at 32 to 35 d after insemination to confirm pregnancy. Data were analyzed using Proc Mixed and Proc Logistic models in SAS (version 9.3; SAS Institute Inc., Cary, NC). Plasma IGF-I concentrations were significantly greater in the primiparous cows than in the multiparous cows, both before and after calving, and were therefore analyzed separately. In multiparous cows plasma IGF-I concentrations postcalving were significantly lower among cows with uterine infection than in those without infection, and multiparous cows with a plasma IGF-I concentration less than 40 ng/mL 1 wk after calving were 3 times more likely to suffer from a uterine infection 4 to 5 weeks postcalving (odds ratio 2.8; 95% confidence interval 1.0-7.6). Plasma IGF-I concentrations were significantly greater after calving in the 121 primiparous cows that exhibited estrus post-CIDR protocol (mean 125 ng/mL) than in the 25 primiparous cows that did not respond (mean 95 ng/mL). Multiparous cows with greater plasma IGF-I concentrations postcalving had a significantly greater chance of conceiving (mean plasma IGF-I concentration of conceiving cows = 86 ng/mL; nonconceiving = 70 ng/mL). These results show an association between greater concentrations of plasma IGF-I postcalving and response to CIDR protocol in primiparous animals (mean plasma IGF-I concentration of responders = 116 ng/mL; nonresponders = 95 ng/mL). In contrast no association was detected between concentrations of plasma IGF-I in relation to the response to the CIDR protocol in multiparous cows. In conclusion, changes in circulating concentrations of plasma IGF-I early postpartum may help predict reproductive status of dairy cows., (Copyright © 2020 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Endometritis is a prevalent post-partum uterine infection in dairy cows resulting in suboptimal reproductive performance. The hypothesis was that endometritis status is associated with suboptimal reproductive performance of postpartum dairy cows managed under zero-grazing feeding practice on smallholder farms. In this study, there was evaluation of effects of endometritis diagnosed at 38.5 ± 14.7 days postpartum (dpp) on subsequent reproductive performance. Reproductive performance of 436 cows from 345 farms was recorded for 210 dpp. Values for reproductive performance indicators were less (P < 0.05) in cows determined to be positive compared to negative for endometritis. Cows that tested positive, as compared to negative, for endometritis had longer periods after parturition until initiation of oestrous cycles (median, interquartile range; 85.0, 57.5-127.0 and 62.6, 49.0-90.0 days, respectively), longer durations before being detected pregnant (95.5, 61.8-145.5 and 63.0, 50.0-83.0 days, respectively), lesser pregnancy rates as a result of the first breeding postpartum (16.5% and 32.7%, respectively), more natural-mating or artificial inseminations per pregnancy (1.3 ± 0.1 and 1.1 ± 0.0, respectively) and more occurrences of anoestrus postpartum (48.4% and 11.7%, respectively). These results provide evidence of a strong association between endometritis and suboptimal fertility performance in zero-grazed cows on smallholder farms in Rwanda. Considering there were 70.2% of cows in the present study were diagnosed with endometritis, this is indicative of a widespread herd health issue, warranting that field veterinary practitioners prioritise endometritis in their herd health service delivery to smallholder dairy farmers for effective disease management and herd sustainability., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background : Streptococcal Toxic Shock Syndrome (STSS) is a serious condition that can arise from streptococcal postpartum endometritis. It is associated with a substantial increase in mortality rate and can rarely result in multiorgan infarction. Early recognition plays a vital role in patients' outcome. Objective : To report a case of complicated STSS and review the literature for previous case reports of streptococcal postpartum endometritis to determine if STSS diagnostic criteria (published by the Centers for Disease Control and Prevention) were fulfilled. Case presentation : This is a 41-year-old woman who presented 5 days after an uncomplicated vaginal delivery with endometritis complicated by invasive group A β-hemolytic streptococcus (GAS) infection and confirmed toxic shock syndrome. The patient was initially admitted to the critical care unit due to hemodynamic compromise requiring intravenous (IV) fluids, IV antibiotic therapy with penicillin and clindamycin, and IV immunoglobulin therapy. The patient subsequently developed multi-organ infarctions, acute respiratory distress syndrome requiring noninvasive respiratory support, and severe reactive arthritis. Literature review revealed 15 case reports of GAS postpartum endometritis, five met criteria for confirmed STSS. One patient died from severe septic shock leading to cardiopulmonary arrest. Thirteen out of 15 cases of postpartum endometritis occurred after uncomplicated vaginal delivery. Conclusion : STSS is a serious and possibly fatal medical condition that requires early diagnosis and treatment to prevent poor patient outcomes and death. Careful consideration to the patient's postpartum clinical presentation with the implementation of an intradisciplinary approach should be utilized.

Background: In several mammals, subfertility or infertility associated with endometritis was reported. Although there have been studies about endometritis in bitches, the pathophysiological mechanisms are not completely known., Aim: This study aimed to evaluate the immunohistochemical expression of Cyclooxygenase 2 (COX2) in clinically healthy bitches with normal uterine tissue and bitches with endometritis., Methods: Forty-eight mixed breed bitches in diestrus were used. Uterine biopsies were collected for diagnosis [normal endometrium ( n = 15; NE), cystic endometrial hyperplasia ( n = 1), atrophy ( n = 2), acute endometritis ( n = 9; AE), subacute endometritis ( n = 7; SE), and chronic endometritis ( n = 14; CE)]. Immunostaining and quantification of positively stained cells was performed on full-thickness uterine biopsies. Data were analyzed by the GLIMMIX procedure of SAS., Results: COX2 immunostaining was scattered and restricted to cells in the stroma in bitches with NE. However, in bitches with endometritis, strong staining was observed in the luminal epithelium, glandular epithelium, and stromal cells. Staining was also observed in inflammatory cells localized in the stroma as well as inside of the glands. The percentage of COX2 positive stromal cells in bitches with AE, SE, and CE was significantly higher compared with NE ( p < 0.005). In addition, the percentage of COX2 positive stromal cells in bitches with SE, and CE was significantly lower compared with AE ( p < 0.003)., Conclusion: COX2 could be involved in the pathophysiological mechanisms producing endometritis without the presence of cystic endometrial hyperplasia in bitches. However, further researches on this topic are required., Competing Interests: The authors declare that there is no conflict of interest.

The adaptation of the uterine environment into a favorable immunological and inflammatory milieu is a physiological process needed in normal pregnancy. A uterine hyperinflammatory state, whether idiopathic or secondary to hormonal or organic uterine disorders (polycystic ovary syndromes, endometriosis/adenomyosis and fibroids), negatively influences the interactions between decidua and trophoblast, early in gestation, and between chorion and decidua later in pregnancy. Abnormal activation of uterine inflammatory pathways not only contributes to the pathogenesis of the obstetric syndromes, i.e. recurrent pregnancy loss (RPL), pre-term delivery (PTD) and pre-eclampsia (PE), but also to correlates with severity. In this review, we summarize recent advances in the knowledge of uterine molecular mechanisms of inflammatory modulation in normal pregnancy and obstetric syndromes (RPL, PTD and PE). In particular, we focus on two regulators of uterine/placental inflammation: the NLRP3 inflammasome and the chemokines decoy receptor D6. We performed comprehensive review of the literature in PubMed and Google Scholar databases from 1994 to 2018. The available evidence suggests that: (i) the expression of inflammasome NLRP3 is increased in the endometrium of women with unexplained RPL, in the chorioamniotic membranes of women with PTL and in the placenta of women with PE; (ii) there is a role for abnormal expression and function of D6 decoy receptor at the feto-maternal interface in cases of RPL and PTD and (iii) the function of placental D6 decoy receptor is impaired in PE. A wider comprehension of the inflammatory molecular mechanisms involved in the pathogenesis of the obstetric syndromes might lead to the identification of new potential therapeutic targets., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To explore the predictive value of endometrial CD138 expression in the natural cycle preceding frozen embryo transfer in patients with normal endometrial dating and histopathologic features, who previously failed the transfer of two high-quality fresh embryos., Design: Retrospective analysis., Setting: University-affiliated hospital., Patient(s): Women with normal endometrial dating and histopathologic features who previously failed the transfer of two high-quality fresh embryos, and who then underwent an endometrial scratching operation preceding a natural cycle., Intervention(s): Paraffin-embedded endometrial samples cut into sections for immunohistochemistry staining of CD138 (syndecan-1) expression, then clinical information for these patients reviewed and analyzed., Main Outcome Measure(s): Clinical rates of pregnancy and implantation., Result(s): A total of 141 women met the inclusion criteria. Of these patients, about 31.2% (44 of 141) were positive for CD138 expression, with CD138 counts ranging from 0 to 33. Receiver operating characteristic (ROC) curves were analyzed to determine whether the number of cells expressing CD138 (CD138 + cells) predicted a successful pregnancy. The areas under the ROC curves based on CD138 + cell density and CD138 + cell count were 0.660 and 0.658, respectively. The clinical pregnancy and embryo implantation rates in patients not expressing CD138 (80.04% and 64.9%, respectively) were statistically significantly higher than rates in CD138 + patients (52.7% and 46.8%, respectively). In addition, the higher the number of cells expressing CD138, the worse the outcome of the pregnancy. Finally, clinical data showed that free pelvic fluid on the day of endometrial sampling (identified using transvaginal ultrasound) might be a risk factor for CD138 expression., Conclusion(s): Endometrial CD138 + count might be a valuable marker predicting pregnancy outcomes after frozen embryo transfer in patients with normal endometrial dating and histopathologic features who previously failed the transfer of two high-quality fresh embryos., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Endometritis, which is usually caused by bacterial infection, is characterized by high levels of pro-inflammatory cytokines and a high infertility rate. Triggering receptor expressed on myeloid cells-1 (TREM-1) has been recognized as a potent amplifier of inflammatory reactions. Studies have demonstrated reduced inflammatory responses and mortality rates of animals with bacterial infection due to the blocking of TREM-1 expression. However, whether TREM-1 deficiency could alleviate the inflammatory reaction in bacterial endometritis is still unclear. Here, TREM-1 knock-out (Trem-1 -/- ) mice were used to inhibit TREM-1 signalling to evaluate its role in inflammatory reactions after a highly pathogenic LPS infection in mice uteri. The results demonstrated that TREM-1 deficiency attenuated the inflammation in mice uteri; markedly reduced the number of polymorphonuclear neutrophils; and suppressed interleukin-1β (IL-1β), IL-6, and tumour necrosis factor-α (TNF-α) concentrations in serum as well as their production in inflamed uteri after LPS stimulation. Our results illustrate an anticipated pathogenic impact of TREM-1 on endometritis during LPS infection and indicate that blocking of TREM-1 in LPS-induced endometritis holds considerable promise for blunting excessive inflammation., (© 2019 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.)

Salpingitis is a common cause for subfertility and infertility both in humans and animals. However, the effects of salpingitis on tubal function and reproductive success are largely unknown. Therefore we set out to investigate the effects of inflammation on sperm and oocyte transport and gameto-maternal interaction in the oviduct using the bovine as a model. For this purpose, oviducts revealing mild (n = 45), moderate (n = 55) and severe (n = 45) inflammation were obtained from cows immediately after slaughter and investigated by live cell imaging, histochemistry and scanning electron microscopy. Our studies showed that endometritis was always correlated with salpingitis. Moderate and severe inflammation caused a significant increase in the thickness of tubal folds (p < 0.05). Severe inflammation was characterized by luminal accumulations of mucus and glycoproteins, increased apoptosis, loss of tight junctions and shedding of tubal epithelial cells. The mean ciliary beat frequency (CBF) in the ampulla was significantly reduced as compared to the controls (p < 0.05). The higher the grade of inflammation, the lower was the CBF (p < 0.001). In severe inflammation, spermatozoa were stuck in mucus resulting in decreased sperm motility. Our results imply that tubal inflammation impairs proper tubal function and leads to reduced sperm fertilizing capacity.

Endometritis in dairy cows is a major global issue and has been associated with a decrease in reproductive performance. The aim of this study was to quantify the effect of endometritis (as defined by the presence of any abnormal vaginal discharge after 21 days post-partum) on post-partum ovarian cyclicity in dairy cows. Milk progesterone analysis was used to monitor reproductive cyclicity in 170 dairy cows across three different commercial herds. Associations between the occurrence of endometritis and the incidence risk of a variety of atypical cycle profiles during the calving to conception period were investigated to establish the importance of endometritis on post-partum ovarian activity. Endometritis increased the incidence odds of atypical ovarian profiles (P < 0.05) with prolonged luteal activity being the most affected (P < 0.05), but also showed prolonged time (3 days) to onset of luteal activity after parturition (P < 0.05). Using milk progesterone analysis, we found a relatively low incidence odds for reproductive cycle problems in healthy cows during the calving to conception period. However, the incidence odds of cycle problems, in particular prolonged luteal activity, were high in cows that had experienced endometritis, which would have significantly impaired reproductive function., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

This study reports on the influence of experimentally-induced uterine inflammation on chemical phenotypes, number and distribution of neurons in the dorsal root ganglia (DRGs) innervating the uterus in sexually mature gilts. On day 17 of the first studied estrous cycle, the uterine horns were injected with retrograde tracer Fast Blue (FB). After 28 days (on an expected day 3 of third studied estrous cycle), 50 ml of either saline (group SAL) or Escherichia coli (E. coli) suspension (10 9 colony-forming units/ml, group E. coli) were injected into each uterine horn. In the control pigs (group CON), only laparotomy was performed. Eight days later DRGs and uteri were collected. All infected gilts developed severe form of acute endometritis. By use of double immunofluorescence labelling the numbers of uterine perikarya expressing substance P (SP), calcitonin gene-related peptide (CGRP), neurokinin A (NKA), galanin (GAL) and pituitary adenylate cyclase-activating polypeptide (PACAP) were analyzed. Injection of E. coli decreased the total number of the FB positive perykaria in the Th10-S4 DRGs. We revealed an increase in the populations of uterine perikarya coded SP + /CGRP - , SP + /NKA - , SP - /NKA + , SP + /GAL + , SP + /GAL - , SP - /GAL + , SP + /PACAP + and SP - /PACAP + . Our results suggest that uterine inflammation affects both the spatial and neurochemical organization pattern of uterine sensory innervation. Additionally, the inflammation may affect the transmission of sensory information from uterus to spinal cord., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The aim of the present study was to clarify the changes in complete blood count, blood biochemistry, and the gene expressions of pro-inflammatory cytokines of peripheral white blood cells in postpartum dairy cows with metritis., Results: The cows were assigned to the control group (n = 28) or the metritis group (n = 28), retrospectively. Blood samples were taken 7 days before the estimated parturition (- 7 d), on the day of parturition (0 d), and 7 and 30 d after parturition. There was no difference in blood indexes between the control group and the metritis group at - 7 d. The WBC, granulocytes and monocytes were generally higher at 7 and 30 d in the metritis group than the control. In comparison with the controls, all liver function parameters and triglyceride levels at 0, 7 and 30 d, and the creatinine level at 7 and 30 d were higher in cows with metritis. The concentrations of Ca and P at 0, 7 and 30 d, and of glucose at 0 d were lower for cows in the metritis group compared with cows in the control group. Among these parameters, the WBC at 30 d, the aspartate aminotransferase activity (AST) at 7 d exceeded normal ranges (WBC: 5.0 ~ 16.0 × 10 9 /L; AST: 42.5 ~ 98 U/L), whereas the concentrations of glucose and Ca from 0 to 30 d were below normal ranges (glucose: 2.5 ~ 4.5 mmol/L; Ca: 2.2 ~ 2.5 mmol/L) in the metritis group. The gene expressions of pro-inflammatory cytokines in the metritis group were higher than those in the control group, including the IL-1α at 7d, the IL-1β at - 7, 0 and 7 d, the IL-6 at - 7, 0, 7 and 30 d, the IL-8 at 0, 7 and 30 d, and the TNF-α at 7 and 30 d., Conclusion: The cows with metritis experienced systemic inflammation for 4 weeks after calving, the impaired hepatic function, and the altered metabolic status with increased triglyceride level and decreased concentrations of glucose, Ca and P.

Bacterial infection of the uterus causes clinical endometritis in 15 to 20% of postpartum dairy cows and reduces fertility, even after the resolution of disease. However, it is difficult to disentangle the mechanisms linking reduced fertility with endometritis because cows have multiple confounding postpartum conditions. The aim of the present experiment was to develop an in vivo model of clinical endometritis in Holstein heifers using pathogenic Escherichia coli and Trueperella pyogenes. Estrous cycles of heifers were synchronized using a 5-d Co-Synch protocol, and subsequently received exogenous progesterone to elevate circulating progesterone at the time of uterine infusion. Endometrial scarification was performed before uterine infusion of live pathogenic Escherichia coli and Trueperella pyogenes, or sterile vehicle. Effects of infusion were evaluated by measuring rectal temperature, plasma haptoglobin, hematology, grading pus in the vaginal mucus, quantifying 16S rRNA in vaginal mucus, and transrectal ultrasonography. Bacterial infusion increased the median vaginal mucus to grade 2 by d 3 postinfusion, and to grade 3 from d 4 to 6 postinfusion. Control heifers maintained a median vaginal mucus grade ≤1 from d 1 to 6. Transrectal ultrasound revealed the accumulation of echogenic fluid in the uterus of heifers following bacterial infusion, which was absent in control heifers. Total 16S rRNA in vaginal mucus was elevated in bacteria-infused heifers compared with control heifers at d 5. Rectal temperature was increased in bacteria-infused heifers. Plasma haptoglobin, general health, and appetite did not differ between groups. As indicated by increased vaginal mucus grade after bacterial infusion and absence of systemic signs of illness, this model successfully induced symptoms resembling clinical endometritis in virgin Holstein heifers. The model allows the isolation of effects of uterine disease on fertility from confounding factors that can occur during the postpartum period in dairy cows., (Copyright © 2019 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Background/aim: Patients diagnosed with chronic endometritis (CE) may fail to respond to standard antibiotic treatment. The driver behind the approach reported here was the imperative need for alternative therapeutic solutions., Case Report: This case report presents a woman with CE and premature ovarian insufficiency having experienced repeated implantation failures following donated embryo transfers. The patient was diagnosed with CE through hysteroscopy, microbiological analysis and scanning electron microscopy. Following the suggested antibiotic treatment, she underwent a new embryo transfer, but with subsequent pregnancy loss. Following a second antibiotic scheme, all diagnostic procedures certified the persistence of CE. The patient underwent autologous, intrauterine platelet-rich plasma treatment and a subsequent embryo transfer. The diagnostic procedures indicated no signs of CE, while the embryo transfer resulted in a twin pregnancy and birth., Conclusion: Platelet-rich plasma may be employed as a first-line CE treatment, especially for patients who fail to respond to conventional antibiotic schemes., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Adenosine monophosphate-activated protein kinase (AMPK) is a highly conserved heterotrimeric complex that acts as an intracellular energy sensor. Based on recent observations of AMPK expression in all structures of the female reproductive system, we hypothesized that AMPK is functionally required for maintaining fertility in the female. This hypothesis was tested by conditionally ablating the two catalytic alpha subunits of AMPK, Prkaa1 and Prkaa2, using Pgr-cre mice. After confirming the presence of PRKAA1, PRKAA2 and the active phospho-PRKAA1/2 in the gravid uterus by immunohistochemistry, control (Prkaa1/2 fl/fl ) and double conditional knockout mice (Prkaa1/2 d/d ) were placed into a six-month breeding trial. While the first litter size was comparable between Prkaa1/2 fl/fl and Prkaa1/2 d/d female mice (P = 0.8619), the size of all subsequent litters was dramatically reduced in Prkaa1/2 d/d female mice (P = 0.0015). All Prkaa1/2 d/d female mice experienced premature reproductive senescence or dystocia by the fourth parity. This phenotype manifested despite no difference in estrous cycle length, ovarian histology in young and old nulliparous or multiparous animals, mid-gestation serum progesterone levels or uterine expression of Esr1 or Pgr between Prkaa1/2 fl/fl and Prkaa1/2 d/d female mice suggesting that the hypothalamic-pituitary-ovary axis remained unaffected by PRKAA1/2 deficiency. However, an evaluation of uterine histology from multiparous animals identified extensive endometrial fibrosis and disorganized stromal-glandular architecture indicative of endometritis, a condition that causes subfertility or infertility in most mammals. Interestingly, Prkaa1/2 d/d female mice failed to undergo artificial decidualization. Collectively, these findings suggest that AMPK plays an essential role in endometrial regeneration following parturition and tissue remodeling that accompanies decidualization.

Metritis in dairy cows has been associated with changes in behavior at the feed bunk, but little is known about the effects on behavior at the lying stall. The aim of this study was to investigate stall use by primiparous dairy cows diagnosed with metritis, specifically time spent in the stall, social interactions at the stall, and lying-related behaviors. After parturition, primiparous cows were housed in a mixed-parity pen with a constant group size of 20. Cows had access to 12 electronic feed bins, 2 electronic water bins, and 24 lying stalls. Four cameras installed above the experimental pen allowed for observation of cows in the feeding and lying area. Every 3 d after parturition, cows were examined for metritis by evaluation of the visual appearance and olfactory character of vaginal discharge. Cows diagnosed with metritis (n = 16) were compared with healthy individuals (i.e., cows without metritis or other clinical disease, n = 16). Healthy individuals were selected based on data availability, body weight, and calving date and, based on these criteria, paired with metritic cows. Video of the 3 d before diagnosis (d -3 to d -1) in the metritic animals (and video from the corresponding days in milk for paired healthy cows) were used to measure behavior. Behaviors assessed included those in the stall (lying, perching, and standing fully in the stall), social behaviors (when a cow either displaced or was displaced by another cow; i.e., actor and reactor replacements), and lying-related behaviors (including visits when the cow entered and left the stall without lying down, aborted lying events when behaviors indicative of the onset of a lying bout were not followed by the cow lying down, and latency to lie down, defined as the time between an aborted lying event and the first lying bout). Cows with metritis spent more time standing fully in the stall on all 3 d, resulting in more time spent standing on d -2 and -1. Cows with metritis tended to have more aborted lying events on d -2, and significantly more on d -1. Cows with metritis tended to be replaced more often at the lying stall on d -3 and tended to have a longer latency to lie down on d -2. We observed no differences between health groups in the number of actor replacements or the number of visits to the stall. In summary, cows with metritis spent more time standing fully in the lying stall and had more aborted lying events. These results suggest that primiparous cows with metritis may be identified by altered behavior at the lying stall., (Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Introduction: Metritis is an uterine pathology that causes economic losses for the dairy industry. It is associated with lower reproductive efficiency, increased culling rates, decreased milk production and increased veterinary costs., Objectives: To gain a more detailed view of the urine metabolome and to detect metabolite signature in cows with metritis. In addition, we aimed to identify early metabolites which can help to detect cows at risk to develop metritis in the future., Methods: We used nuclear magnetic resonance spectroscopy starting at 8 and 4 weeks prior to the expected day of parturition, during the week of diagnosis of metritis, and at 4 and 8 weeks after diagnosis of metritis in Holstein dairy cows., Results: At 8 weeks before parturition, pre-metritic cows had a total of 30 altered metabolites. Interestingly, 28 of them increased in urine when compared with control cows (P < 0.05). At 4 weeks before parturition, 34 metabolites were altered. At the week of diagnosis of metritis a total of 20 metabolites were altered (P < 0.05). The alteration continued at 4 and 8 weeks after diagnosis., Conclusions: The metabolic fingerprints in the urine of pre-metritic and metritic cows point toward excretion of multiple amino acids, tricarboxylic acid cycle metabolites and monosaccharides. Combination of galactose, leucine, lysine and panthotenate at 8 weeks before parturition might serve as predictive biomarkers for metritis.

The objective of this research was to determine the effect of disease misclassification on the estimated effect of metritis on milk production. Misclassification introduces bias that usually results in an underestimation of the association between exposure (disease) and the outcome of interest (milk production). This distorted measure of association results from the comparison of an affected population (some of which may not truly be affected) to a nonaffected population (which often includes affected subjects that are unidentified). A convenience sample of DairyComp305 (Valley Agricultural Software, Tulare, CA) data representing 1 yr of calvings (n = 3,277) from 1 Midwestern Holstein herd was used. This herd was chosen because of its ongoing efforts to consistently and completely record all clinical diseases, including the incidence of both mild and severe metritis cases. Metritis was defined as the presence of a flaccid uterus containing fetid fluids or a foul watery discharge within 14 d of calving. Cows that appeared clinically normal other than the discharge were considered mild and those with systemic signs of disease were classified as severe. The original data set included metritis recorded as mild, severe, or not recorded (NR), where no metritis was observed, and was considered to contain the metritis true severity (TrS). First, to evaluate the effect of misclassification bias, we retrospectively randomized 45% of mild metritis to be classified as NR to simulate inconsistent disease recording (IR); then, in a separate model, all mild metritis cases were changed to NR to simulate a situation of very poor disease recording (PR), where only the most severe cases are recorded. The TrS, IR, and PR data sets were analyzed separately in JMP (SAS Institute Inc., Cary, NC). An ANOVA was conducted for second test 305-d mature-equivalent milk projection (2nd305ME), and nonsignificant variables were removed, but the variable metritis was forced into all models. Based upon the TrS model, adjusting for effects of lactation group, month of calving, dystocia, twins, retained placenta, early-lactation mastitis, displaced abomasum, and significant interactions, a case of mild metritis was associated with 384 kg less 2nd305ME and a case of severe metritis was associated with 847 kg less 2nd305ME compared with no metritis. For the IR model, a case of mild metritis was associated with 315 kg less 2nd305ME and a case of severe metritis was associated with 758 kg less 2nd305ME compared with no metritis. For the PR model, severe metritis was associated with 680 kg less 2nd305ME compared with NR. The IR and PR models underestimated 2nd305ME loss for severe metritis cases by 89 and 166 kg/cow, and resulted in 180,441 and 330,256 kg of total milk loss unaccounted for at the herd level, respectively, compared with TrS. Overall, misclassification of metritis cases results in greater bias and largely underestimates the true association between metritis and the consequence costs of the disease., (The Authors. Published by FASS Inc. and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).)

Potential beneficial effects of lactic acid bacteria on the genital health of cows become of particular interest when considering the importance of an optimal uterine health status for the success of breeding in dairy farming. Therefore, the aim of the present study was to analyse the influence of an intrauterine administration of the Lactobacillus buchneri DSM 32407 on reproductive performance, uterine health status, endometrial mRNA expression of pro-inflammatory factors of cows with signs of subclinical endometritis (SCE). L. buchneri DSM 32407 (n = 56; [LAC]) or a placebo (n = 60; [PLA]) was administered on day 24-30 postpartum. Endometrial cytobrush samples of cows with SCE were taken before the administration and at three following weeks (n = 16 cows each for LAC/SCE and PLA/SCE). A higher proportion of cows of the LAC and LAC/SCE group was pregnant after the first service and median days to conception for cows pregnant on day 200 pp were shorter. Three weeks after the administration, the endometrial mRNA expression of CXCL1/2, CXCL3, CXCR2, IL1B, IL8 and PTPRC was lower in the LAC/SCE group compared with the PLA/SCE group. These findings suggest that the presence of L. buchneri DSM 32407 contributes to a uterine environment that results in a better reproductive performance.

Background: Chronic endometritis (CE) is a continuous inflammation of uterine endometrium, and it is usually symptomless. As CE has been thought not to affect the reproductive status and general health of affected women, its significance has not been explored. However, recent studies have shown that CE is related with repeated implantation failures after in vitro fertilization-embryo transfer, unexplained infertility, and recurrent miscarriages. As decidua differentiates to support the implantation process and maintains the pregnancy, we hypothesized that CE may influence the process of decidualization., Methods: Seventeen patients were employed in the experiment involving culture of endometrial stromal cells (ESCs). After obtaining endometrial samples, ESCs were harvested and cultured for 13 days. The concentrations in culture media and the protein expressions in ESCs of prolactin (PRL) and insulin-like growth factor binding protein-1 (IGFBP-1), two well known decidualization markers used in a large number of in vitro models, were analyzed by ELISA and Western blotting, respectively, and the cell numbers were also counted. The mRNA levels of PRL and IGFBP-1 were tested by quantitative real time polymerase chain reaction (RT-PCR). Since sex hormone induce proliferation and differentiation to decidua via binding to the sex hormone receptors (ERα, ERβ, PRA, and PRB), their expression was assessed in another 17 patients' paraffin-embedded endometrial tissue specimens by immunohistochemistry and semi-quantified by H-score., Results: Increased cell numbers and reduced secretion of PRL and IGFBP-1 were detected by ELISA in the ESCs of CE patients after culture for 13 days compared with non-CE patients. The decreased protein expression of IGFBP-1 in ESCs of CE patients was detected by Western blotting. The decreased expression of PRL mRNA and IGFBP-1 mRNA were detected by RT-PCR. Increased expressions of ERα, ERβ, PRA, and PRB were observed in the stromal cells of CE patients in comparison to non-CE patients, whereas increased expressions of ERα and ERβ were detected in the glandular cells of CE., Conclusion: Our data suggests that CE modifies decidualization of human ESC through untuning the function of sex steroid hormone receptor.

Nitric oxide (NO) may have a role in persistent breeding-induced endometritis in mares through an inhibitory effect on uterine contractility. The objectives of this study were to test the effect of NO on spontaneous uterine contractility in-vitro and to evaluate whether this effect varied between the longitudinal and circular muscle layers of the uterus. Reproductive tracts were collected from eight euthanized non-pregnant mares (age 4-19 years; body weight 405-530 kg). Transrectal examination of the reproductive tract was performed before euthanasia to evaluate stage of the estrous cycle and presence of any apparent abnormality. After euthanasia, one uterine tissue sample was collected for histological evaluation and four full-thickness uterine tissue strips (10-12 mm × 2 mm), two parallel to each muscle layer, were excised for in-vitro contractility evaluation. Strips were suspended in tissue chambers containing Krebs-Henseleit solution, with continuous aeration (95% O 2 -5% CO 2 ; pH 7.4) at 37 °C. After equilibration, spontaneous contractility was recorded (pre-treatment) and strips excised in each direction were randomly allocated to each of two groups: 1) SNAP (S-nitroso-N-acetylpenicillamine, an NO donor); or 2) NAP (N-acetyl-d-penicillamine, vehicle and time-matched control). These were treated at 15 min intervals with increasing concentrations (10 -7  M to 10 -3  M) of SNAP and NAP, respectively. Contractility data was recorded throughout the experiment. An interaction effect of group-by-concentration was observed (P < 0.0001). The mean contractility after treatment with 10 -4  M and 10 -3  M SNAP were significantly lower than the pre-treatment contractility and the mean contractility after treatment with lower SNAP concentrations. In contrast, contractility did not change significantly in the NAP treated controls. The effect of treatment on uterine contractility was not influenced by age or weight of the mare, stage of estrous cycle, uterine histology grade, or muscle layer. Secondary findings included significant main effects of stage of estrous cycle (increased contractility in estrus compared to diestrus), uterine histology grade (decreased contractility in grade IIB compared to grade I) and age (decreased contractility in mares aged > 8 years compared to mares aged ≤ 8 years). In conclusion, results of this study indicate that NO has a dose-dependent inhibitory effect on spontaneous uterine contractility irrespective of the muscle layer in the mare., (Copyright © 2017 Elsevier Inc. All rights reserved.)

This study was conducted to evaluate the effects of induced endometritis on uterine blood flow in cows. Transrectal Doppler sonography was performed on uterine arteries of six cyclic cows before and for 4 days after inducing acute endometritis by intrauterine infusion of 720 mg of policresulen, and for 4 days of the following estrous cycle. Time-averaged maximum velocity (TAMV) increased (p < 0.001) and pulsatility index (PI) decreased (p < 0.0001) within 1 h of policresulen administration, and did not change (p > 0.05) in the next 4 days of the same cycle. TAMV and PI values in the subsequent cycle did not differ (p > 0.05) from the values measured before infusion and showed no changes (p > 0.05) within the cycle. Blood flow parameters were not related (p > 0.05) to plasma concentrations of progesterone and estrogen. All cows showed an acute endometritis determined by histopathological findings of biopsy samples taken 1 day after infusion and fibrotic endometrial alterations detected in the subsequent cycle. No relationships were observed between fibrotic changes of the endometrium and uterine blood flow during either cycle. In conclusion, acute inflammation is accompanied by a rise in uterine blood flow, but fibrotic alterations do not seem to be related to Doppler sonographic findings.

The objectives of this study were to evaluate the reproductive and productive performance of dairy cows with and without puerperal metritis and to evaluate the effectiveness of using a long-acting ceftiofur preparation. Dairy cows in one dairy farm, calving from July 2009 to January 2010, were examined between 3 and 14 days postpartum and classified on the basis of vaginal discharge into three groups: cows with normal discharge (control; C); cows with a bloody mucus purulent or pathologic nonfetid discharge (PnFD), and cows with bloody mucopurulent or purulent fetid discharge (PFD). Cows in C and PnFD groups were not treated, whereas those in the PFD group were randomly allocated to receive 2.2 mg/kg of ceftiofur subcutaneously behind the ear (PFD-T) or remain untreated (PFD-No T). From the 640 cows examined, 58.2% formed the C group, 13.4% formed the PnFD group, and 28.4% formed the PFD group. Survival curves differed between cows in the C group and PFD-No T group (P = 0.0013) and between PFD-No T versus PFD-T group (P = 0.0006). Survival curves of PnFD were intermediate and did not differ from those in the C group (P = 0.2) and PFD-T group (P = 0.1) but tended to be different from the PFD-No T group (P = 0.056). The postpartum interval to achieve a 25% pregnancy rate was 72 days for cows in the C group, 73 days for the PFD-T group, 83 days for PnFD group, and 95 days for the PFD-No T group. The chance of pregnancy in a cow in the C group was 1.98 times higher (95% confidence interval = 1.33, 3.08) and in cows in the PFD-T group was 2.16 times higher (95% confidence interval = 1.37, 3.50) than that in the PFD-No T group. Finally, the chance of pregnancy in cows in the PnFD group tended to be higher (P = 0.08) than that in the PFD-No T group but did not differ from the other two groups. Cumulative 305-day milk production was higher (P < 0.0001) in C group than those with vaginal discharge, regardless of fetidness and regardless of treatment. It is concluded that puerperal metritis affects the reproductive and productive performance of dairy cows and the treatment with ceftiofur was effective in reducing the adverse effects on reproductive performance but not on milk production., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The aim of the study was to investigate the effect of Bovine Herpesvirus 4 (BoHV-4) and Histophilus (H.) somni on fertility rate of cows in a Hungarian Holstein-Friesian dairy herd with purulent vaginal discharge (PVD). Non-pregnant cows (n = 188) with mature corpus luteum were treated with cloprostenol and 3 days later if they did not show oestrus, were examined by rectal palpation. Animals showing PVD (n = 60/31.9%/) and 14 controls with normal vaginal discharge (Score 0) were randomly selected and further examined by ultrasonography and blood samples were collected for detecting BoHV-4 DNA and transcervical guarded swabs were collected from the uterus for bacteriological examination. Although the majority of the examined animals were infected with BoHV-4 and H. somni including the control animals as well, in group of animals with PVD score 3, fewer animals became pregnant and the duration between the first treatment to pregnancy was significantly extended. Based on these clinical and comparative data, our results confirm that these two microorganisms together may impair important reproductive parameters which may cause large economic losses to dairy farms., (© 2015 Blackwell Verlag GmbH.)

The objective of this study was to determine whether cervicitis in dairy cows is an independent disease or occurs concomitantly with inflammation of the uterus, and to clarify possible effects of cervicitis on reproductive performance. Dairy cows (n = 416) from 33 dairy farms were examined by rectal palpation and vaginoscopy between 42 and 50 days postpartum. Inclusion criteria for this study were absence of abnormal vaginal discharge and abnormalities of the uterus (fluctuation) at rectal palpation. Cervicitis was diagnosed when the second cervical fold was swollen and prolapsed with (C2) or without (C1) reddening. Cytobrush samples from the uterus (n = 370) and the cervix (n = 402) were collected, and the percentage of neutrophils in the uterus (PMNU) and the cervix as indicators of inflammation (threshold: ≥5%) was determined. In addition, endometrial biopsies for histology were collected, 300 of which were suitable for evaluation. Cervicitis (C1/C2) was diagnosed in 253 of 416 (60.8%) of cows. Of these, the prolapsed cervical mucosa was hyperemic (C2) in 29.1% of cases. Of 370 available uterine cytology samples, 221 cows had a clinical cervicitis; however, 170 (76.9%) had PMNU less than 5%. Of 300 uterine histologic examinations, 82 (27.3%) did not reveal any abnormalities; the remaining cows either had uterine inflammation and/or degenerative uterine changes such as endometriosis and angiosclerosis. Furthermore, of 300 biopsied animals, 184 revealed a cervicitis (C1/C2); however, 30.4% of these animals had no histopathologic uterine findings. For further analysis, only animals either without histopathologic findings and normal uterine cytology or with solely endometritis (defined as PMNU ≥ 5% and/or positive histopathology of the uterine tissue) were evaluated (n = 157). Of these, 95 cows had cervicitis. Unexpectedly, 63 of 95 (66.3%) cows had cervicitis without endometritis. With regard to reproductive performance, days to first service were not affected by cervicitis. Number of days open in animals with cervicitis but without endometritis tended to be lower than in cows with cervicitis plus endometritis (P = 0.092). Also, number of days open relative to percentage of neutrophils greater than 5% was lower when the cervical compared to the uterine mucosa was affected (P < 0.05). Total conception and pregnancy rates of animals 200 days into lactation decreased significantly in cows with severe cervical inflammation (C2). In conclusion, the results of this study suggested that cervicitis occurs independent of endometritis, and a higher degree of cervicitis is associated with poorer reproductive performance., (Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.)

The process of implantation is highly complex and involves a delicate interplay between the embryo and the appropriate maternal environment. The failure to implant is thought to be due to maternal factors or embryonic factors. Inflammation can be a part of the normal physiologic process during implantation; however, there are also pathologic entities that adversely affect uterine receptivity. This review will focus on chronic endometritis and hydrosalpinges as two specific inflammatory processes that contribute to implantation failure. For both chronic endometritis and hydrosalpinges, we will review the diagnosis, pathophysiology, and effect on implantation following treatment. The existing literature conclusively demonstrates that hydrosalpinges should be addressed by either laparoscopic salpingectomy or proximal tubal occlusion prior to in vitro fertilization. The picture for chronic endometritis is less clear since the diagnosis and treatment of chronic endometritis are not standardized, and there are no available randomized controlled trials on this topic. Future studies may target gene expression arrays as a method for further elucidating the role of inflammatory markers in normal and abnormal implantation processes., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

The effect of leukotriene (LT) C4 (LTC4) and LTD4 on the contractility of an inflamed porcine uterus was investigated. On Day 3 of the estrous cycle (Day 0 of the study), either saline or Escherichia coli suspension was injected into each uterine horn. Although acute endometritis developed in all bacteria-inoculated gilts, a severe acute endometritis was noted more often on Day 8 than on Day 16. Myometrial and endometrial/myometrial strips were incubated with LTC4 or LTD4 alone, or together with a cysteinyl-LT receptor antagonist (BAY-u9773). Leukotriene C4 increased the contraction intensity in the saline- and bacteria-treated uteri on Day 8; however, its effect was lower in the myometrium of inflamed uteri. Contraction frequency was found to decrease in the saline-treated uteri as opposed to inflamed ones, in which it was elevated. On Day 16, contraction intensity increased in response to LTC4 in the saline-treated uteri but was reduced in the inflamed organs. The value of this parameter was lower in the inflamed uteri than that in the saline-treated ones. Leukotriene D4 (Days 8 and 16) augmented contractility in the saline-treated uteri, but despite increasing its intensity in the inflamed organs, it decreased contraction frequency. Leukotriene C4 or LTD4, added to BAY-u9773-pretreated saline- and bacteria-treated uteri on both days, decreased the contraction intensity. On Day 16 after treatment with BAY-u9773 and LTC4, contraction intensity in the endometrium/myometrium of the inflamed uteri was lower than that in the saline-treated organs. Data show that both LTC4 and LTD4 affect the contractility of inflamed porcine uteri, though LTC4 exerts a weaker contractile effect., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To evaluate the alterations in endometrial waves (EW) originating from the contraction of the subendometrial myometrial layer in the periovulatory and midluteal phases in women diagnosed with chronic endometritis (CE)., Design: Case-control study., Setting: University hospital., Patient(s): Forty-five women referred for hysteroscopy and diagnosed with CE., Intervention(s): Three-minute recording of transvaginal ultrasound scanning on sagittal uterine plane at periovulatory (cycle days 11-14) and midluteal phase (cycle days 19-22)., Main Outcome Measure(s): Direction and frequency of EW measured by transvaginal ultrasound scan., Result(s): The direction and frequency of EW were analyzed offline as accelerated (four to eight times normal speed) image sequences using video editing software, and the results were compared with 45 cycling women without CE. The EW pattern was significantly different when comparing the women with CE and controls at both the periovulatory and midluteal phases. During the periovulatory phase, we observed retrograde contractions in 26.7% versus 88%, anterograde in 24% versus 0, opposing in 22.7% versus 12%, not propagated in 13.3% versus 0, and absent in 13.3% versus 0, respectively, in the CE cases versus the control group. During the midluteal phase, we observed not propagated (41.3% vs. 61.3%), opposing (24% vs. 25.4%), absent (16.1% vs. 13.3%), anterograde (13.3% vs. 0), and retrograde (5.3% vs. 0), respectively, in the CE cases versus the control group., Conclusion(s): Women with CE show altered EW patterns in both the periovulatory and midluteal phases. Altered uterine contractility may aid in explaining the symptoms related to CE such as pain, abnormal uterine bleeding, infertility, and possibly endometriosis., (Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Study Question: What is the prevalence of chronic endometritis (CE) in women with repeated unexplained implantation failure (RIF) at IVF, and how does antibiotic treatment affect the reproductive outcome?, Summary Answer: Chronic endometritis, associated with infection with common bacteria or mycoplasma, is common in women complaining of RIF and antibiotic treatment significantly improves the reproductive outcome at a subsequent IVF cycle., What Is Known Already: We have reported that CE is a frequent finding in women with repeated pregnancy loss and a significantly higher rate of successful pregnancies was achieved after adequate antibiotic treatment. Moreover, CE was identified in 30.3% of patients with repeated implantation failure at IVF and women diagnosed with CE had lower implantation rates (11.5%) after IVF cycles. In contrast, other authors reported that the clinical implication of CE should be considered minimal and that the reproductive outcome at IVF/ICSI cycles was not negatively affected by CE., Study Design, Size, Duration: A retrospective study was performed from January 2009 through June 2012 on 106 women with unexplained infertility and a history of RIF., Participants/materials, Setting, Methods: All patients underwent hysteroscopy and endometrial sampling for histology and microbiological investigations. Women diagnosed with CE underwent antibiotic treatment and the effect of treatment was confirmed by hysteroscopy with biopsy. Within 6 months after treatment all women had a further IVF attempt. The IVF outcomes were compared in women without signs of CE (Group 1) and persistent CE (Group 2) after antibiotic treatment. Clinical pregnancy rate (PR), and live birth rate (LBR) were compared at post-treatment IVF attempt., Main Results and the Role of Chance: Seventy (66.0%) women were diagnosed with CE at hysteroscopy. In 61 (57.5%) CE was confirmed by histology and 48 (45.0%) by cultures. Common bacteria and mycoplasma were the most prevalent agents. In 46 (75.4%) out of 61 women, with diagnosis of CE at hysteroscopy and histology, examinations were normal after appropriate antibiotic treatment control (Group 1) while in 15 (24.6%) cases signs of CE were still present (Group 2). At IVF attempt after treatment, a significantly higher PR and LBR was reported in women from Group 1 compared with women from Group 2 (65.2 versus 33.0% P = 0.039; 60.8 versus 13.3%, P = 0.02, respectively)., Limitations, Reasons for Caution: Possible biases related to retrospective studies and to preferential referral of patients with CE, and limited number of cases., Wider Implications of the Findings: A prospective randomized clinical trial is needed to confirm our findings but in women with RIF a hysteroscopic evaluation of the uterine cavity to exclude CE should be considered and appropriate antibiotic treatment should be given before submitting the patient to a further IVF attempt., (© The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Subclinical endometritis (SEM) is poorly investigated in beef cows, as stated in the literature. This project aims to evaluate the rate and the consequences of SEM in Piedmontese cows, with a focus on bacteriological findings and fertility parameters. Uterine cytology was performed for 97 subjects; a total of 31% of the cows were diagnosed as being positive for SEM and as having an 8% neutrophil (PMN) presence on the slide, which is considered as the best cut-off to diagnose the pathology. Only 13% of the cows positive for SEM were pregnant within 130 dpp and generally showed increases of 40 days in the partum to conception interval compared with the negative cows (142 vs 182, p = 0.01). Cows positive for both bacteriology and cytology showed a lower fertility than cows with only inflammation or only a bacterial presence (p = 0.0004). Bacterial isolation detected different species, but no difference in regard to the impact of these bacteria on SEM was shown. Parity, presence of calves, hygiene condition, age and number of service did not affect whether a cow was positive for subclinical endometritis (p < 0.05). The housing system (free stalls vs tie stalls) used seems to affect the SEM rate in Piedmontese cows; cows bred in tie stalls were more likely to be positive for SEM (OR = 2.2; p = 0.04). In conclusion, cytology seems to be a good technique for the diagnosis of subclinical endometritis in beef cows, and as in dairy cows, subclinical endometritis has a detrimental effect on fertility, causing an increase in partum to conception and a decrease in the rate of cows who become pregnant within 130 dpp, particularly for those cows housed in a tie stall., (© 2014 Blackwell Verlag GmbH.)

The objective of the present work was to study the functional characteristics of the microcirculation system in the women of late reproductive age presenting with chronic endometritis before and after a course of contrast massage. Three types of functional changes in the microcirulation system were distinguished based on the results of laser-assisted Doppler flowmetry. All of them were characterized by high coefficients of correlation with the results of dopplerometry of uterine blood flow and underwent dynamic changes in the course of the treatment. The study has demonstrated the high therapeutic effectiveness of the contrast massage technique as a tool for inducing hemodynamic changes in the small pelvis basin in the women suffering from chronic endometritis.

Multiparous Holstein cows (n=108) were used to determine the associations of cytological endometritis (CE) with plasma nonesterified fatty acids (NEFA) and β-hydroxybutyrate (BHBA) as markers of energy metabolism, calculated energy balance (EB), and plasma haptoglobin (Hp) as a marker of inflammation during the periparturient period and early lactation. Evaluation of endometrial cytology by low-volume uterine lavage was conducted on 1d between 40 and 60 d postcalving. The incidence of CE among cows sampled was 40%. The area under the curve (AUC) was calculated for both NEFA and BHBA using data collected from 3 wk before to 3 wk after parturition. Data for NEFA and BHBA AUC were stratified into prepartum (wk -3 to parturition) and postpartum (parturition to wk +3) for statistical analysis. Prepartum AUC for neither NEFA nor BHBA was associated with subsequent CE; however, cows that subsequently developed CE tended to have higher postpartum AUC for NEFA and had higher postpartum AUC for BHBA. Consistent with the results for plasma NEFA and BHBA, calculated EB during the prepartum period was not different in cows that did or did not develop CE; however, cows with CE had lower EB during the 6-wk postpartum period compared with cows without CE. Analysis of EB by week (wk -3 to -1 before calving and wk +1 to +6 postcalving) indicated that EB in cows with CE was lower at wk +1, +2, and +3 and tended to be lower at wk +6 than cows without CE. Plasma Hp concentrations were analyzed from wk +1 to +8 of lactation; concentrations of Hp were not different during either wk +1 or the entire postpartum period between cows that did or did not develop CE. These results suggest that lower energy status during the first 3 wk postpartum, but not necessarily systemic inflammation, is associated with subsequent development of CE., (Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the association between endometriosis and chronic endometritis., Methods: Endometrial specimens were obtained from 71 patients, 34 with endometriosis (endometriosis group) and 37 without endometriosis (non-endometriosis group), who underwent hysterectomy, and the specimens were immunostained for the plasmacyte marker CD138. The rate of chronic endometritis was compared between the endometriosis group and the non-endometriosis group. Furthermore, the 71 patients were also divided into two groups, 28 with chronic endometritis (chronic endometritis group) and 43 without chronic endometritis (non-chronic endometritis group). Logistic regression analysis was performed with variables including age, body mass index (BMI), gravidity and parity, and diagnoses of leiomyoma, adenomyosis, and endometriosis on pathology to examine the independent effect of each variable on chronic endometritis. Patients suffering from cervical invasive carcinoma, endometrial carcinoma, and endometrial polyps or treated with gonadotropin-releasing hormone agonists, progestins, or oral contraceptives before surgery were excluded., Results: Chronic endometritis was identified in 52.94% of the endometriosis group and 27.02% of the non-endometriosis group (p<0.05). Logistic regression analysis revealed that endometriosis was associated with chronic endometritis., Conclusions: This result suggests a strong association between endometriosis and chronic endometritis.

Background: Disturbed uterine involution impairs ovarian function in the first weeks after calving. This study analyzed the long-term effect of metritis on luteal function of 47 lactating Holstein-Friesian cows during the first four postpartum estrous cycles. Cows with abnormal uterine enlargement and malodorous lochia were classified as having metritis (group M, n = 18), and all others were considered healthy (group H, n = 29). Luteal size was measured once between days 9 and 13 of the first (group H, n = 11; group M, n = 12), second (group H, n = 23; group M, n = 18) and fourth (group H, n = 11; group M, n = 7) postpartum luteal phases. Serum progesterone concentration was measured at the same time. Sixteen cows (group H, n = 9; group M, n = 7) underwent transvaginal luteal biopsy for gene expression analysis of steroidogenic regulatory proteins during the second and fourth cycles. Cows with persistence of the corpus luteum (CL) underwent determination of luteal size, luteal biopsy and serum progesterone measurement once between days 29 and 33, followed by prostaglandin treatment to induce luteolysis. The same procedures were repeated once between days 9 and 13 of the induced cycle., Results: The cows in group M had smaller first-cycle CLs than the cows in group H (p = 0.04), but progesterone concentrations did not differ between groups. Luteal size, progesterone concentration and gene expression did not differ between the two groups during the second and fourth cycles. Compared with healthy cows (10%), there was a trend (p = 0.07) toward a higher prevalence of persistent CLs in cows with metritis (33%). Persistent CLs were limited to the first cycle. Persistent CLs and the induced cyclic CLs did not differ with regard to the variables investigated., Conclusions: An effect of metritis on luteal activity was apparent in the first postpartum estrous cycle. However, after the first postpartum cycle, no differences occurred in analyzed parameters between metritis and control cows. Therefore, a metritis is able to impair luteal activity transiently, but does not seem to have a long-term effect on luteal function.

Persistence of free fluid in the uterine lumen of bitches with endometrial hyperplasia appears to be diagnostic for mating-induced endometritis and is associated with reduced chances of pregnancy. This study investigated the possibility that reduced fertility might be associated with an effect of uterine fluid on sperm. Uterine lavage fluid was collected pre- and post-insemination from normal bitches without ultrasonographically-detectable luminal fluid (n=4), and previously non-pregnant bitches with endometrial hyperplasia and luminal fluid (n=4). Concentrations of polymorphonuclear neutrophils (PMNs) were measured and the effect of the fluid on the attachment of spermatozoa to the uterine epithelium was studied using medium (M) 199 as a control. To elucidate whether any effect was accounted for by the presence of PMNs, attachment was also measured in M199 with PMNs added at the concentration found in lavage fluid. Pre-insemination lavage fluid from both groups contained low concentrations of PMNs which increased post-insemination; the increase was larger for bitches with uterine fluid. Compared with M199 controls, lavage fluid reduced the attachment of spermatozoa; fluid from bitches with endometrial hyperplasia and uterine fluid had a greater effect than normal bitches, and post-insemination fluid had a greater effect than pre-insemination fluid. Spermatozoal attachment was reduced by a similar magnitude for M199 with added PMNs, although post-insemination fluid from bitches with endometrial hyperplasia reduced attachment more than M199 with added PMNs. Poor fertility in bitches with uterine luminal fluid might be partially associated with impaired attachment of spermatozoa to uterine epithelium, mediated principally, but not solely, by PMN influx into the uterine lumen., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The materno-fetal transfer of nanoparticles is a critical issue in designing theranoustic nanoparticles for in vivo applications during pregnancy. Recent studies have reported that certain nanoparticles can cross the placental barrier in healthy pregnant animals depending on the size and surface modification of the nanoparticles and the developmental stages of the fetuses. However, materno-fetal transfer under pathological pregnant conditions has not been examined so far. Here, it is shown that intrauterine inflammation can enhance the materno-fetal transfer of nanoparticles in the late gestation stage of murine pregnancy in a size-dependent manner. Three different-sized gold nanoparticles (Au NPs) with diameters of 3 (Au3), 13 (Au13) and 32 (Au32) nm are applied. The accumulation of Au3 and Au13 nanoparticles in the fetuses is significantly increased in intrauterine inflammatory mice compared with healthy control mice: the concentration of Au3 is much higher than Au13 in fetal tissues of intrauterine inflammatory mice. In contrast, Au32 nanoparticles cannot cross the placental barrier either in healthy or in intrauterine inflammatory mice. The possible underlying mechanism of the increased materno-fetal transfer of small-sized nanoparticles on pathological conditions is inferred to be the structural and functional abnormalities of the placenta under intrauterine inflammation. The size of the nanoparticles is one of the critical factors which determines the extent of fetal exposure to nanoparticles in murine pregnancy under inflammatory conditions., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Intrauterine inflammation adversely affects cardiopulmonary, systemic, and cerebral hemodynamics in preterm neonates, but its impact on responses to endotracheal tube (ETT) suction, known to affect hemodynamics, is unknown. We hypothesized that intrauterine inflammation would alter the cardiopulmonary and cerebral hemodynamic response to open ETT suction in preterm lambs., Methods: Chronically instrumented fetuses received intra-amniotic lipopolysaccharide (LPS; to induce intrauterine inflammation) or saline at 118 d of gestation (term ~147 d). At 125 d of gestation, lambs were delivered and mechanically ventilated. Open ETT suction was performed 30 min after delivery. Pulmonary and cerebral arterial pressures and flows were recorded continuously., Results: Intrauterine inflammation reduced pulmonary blood flow (PBF) and increased pulmonary vascular resistance (PVR) after preterm birth. PBF and left-ventricular output (LVO) increased during and immediately after ETT suction in both groups, but the values were higher in LPS-exposed lambs. Preductal oxygenation significantly decreased during ETT suction but to a greater extent in LPS-exposed lambs. Cerebral blood flow and systemic arterial pressure were increased by open ETT suction similarly in the two groups., Conclusion: Intrauterine inflammation exacerbates the neonatal hemodynamic response to open ETT suction.

Background: In our model of a congenital heart defect (CHD) with increased pulmonary blood flow (PBF; shunt), we have recently shown a disruption in carnitine homeostasis, associated with mitochondrial dysfunction and decreased endothelial nitric oxide synthase (eNOS)/heat shock protein (Hsp)90 interactions that contribute to eNOS uncoupling, increased superoxide levels, and decreased bioavailable nitric oxide (NO). Therefore, we undertook this study to test the hypothesis that L-carnitine therapy would maintain mitochondrial function and NO signaling., Methods: Thirteen fetal lambs underwent in utero placement of an aortopulmonary graft. Immediately after delivery, lambs received daily treatment with oral L-carnitine or its vehicle., Results: L-Carnitine-treated lambs had decreased levels of acylcarnitine and a reduced acylcarnitine:free carnitine ratio as compared with vehicle-treated shunt lambs. These changes correlated with increased carnitine acetyl transferase (CrAT) protein and enzyme activity and decreased levels of nitrated CrAT. The lactate:pyruvate ratio was also decreased in L-carnitine-treated lambs. Hsp70 protein levels were significantly decreased, and this correlated with increases in eNOS/Hsp90 interactions, NOS activity, and NOx levels, and a significant decrease in eNOS-derived superoxide. Furthermore, acetylcholine significantly decreased left pulmonary vascular resistance only in L-carnitine-treated lambs., Conclusion: L-Carnitine therapy may improve the endothelial dysfunction noted in children with CHDs and has important clinical implications that warrant further investigation.

A vast majority of the world buffalo resource is concentrated in tropical and subtropical countries. Apart from heat stress and poor nutritional availability, endometritis is one of the most commonly encountered reproductive problems limiting fertility and consequently productive potential of the species. As demonstrated recently, endometritis impairs growth and follicular fluid composition of the largest follicle in buffalo. In the present study, the effect of endometritis on luteal development, function, nitric oxide (NO), and ascorbic acid was investigated. Reproductive tracts were collected from 90 cyclic buffaloes at an abattoir and grouped into endometritic (n = 36) or non-endometritic (n = 54) buffaloes based on physical examination of uterine mucus, white side test, and uterine cytology. Samples with pus-containing mucus, positive reaction on white side test, and/or >5 % neutrophils were considered to be positive for endometritis. Corpora lutea were enucleated, weighed, classified into stages I to IV, and assayed for progesterone (P(4)), NO, and ascorbic acid concentrations. Endometritic buffaloes had lesser (P < 0.0001) luteal weight and P(4), NO, and ascorbic acid concentrations than non-endometritic buffaloes. The findings indicated that endometritis impairs corpus luteum development and function in buffalo. Reduced luteal NO and ascorbic acid concentrations during endometritis are novel findings.

The goal of the study was to estimate the content of prostacyclin (PGI(2)), the levels of PGI synthase (PTGIS) and receptor (PTGIR) protein expression, and the cellular localization of these factors in the inflammatory-changed porcine uterus. The effect of PGI(2) on the contractility of the inflamed uteri was also determined. On Day 3 of the estrous cycle (Day 0 of the study), 50 mL of either saline or Escherichia coli suspension (10(9) colony-forming units/mL) were injected into each uterine horn. Acute endometritis developed in all bacteria-inoculated gilts, however on Day 8 of the study a severe form of acute endometritis was noted more often than on Day 16. Bacteria injections increased the contents of 6-keto-prostaglandin F(1α) in endometrium, myometrium, washings, and the level of PTGIS in endometrium on Days 8 and 16, and the content of PTGIR in endometrium on Day 16. In the inflamed uteri on both study days, stronger immunoreactivity for PTGIS was observed in part of the luminal and glandular epithelial cells and in a portion of the endometrial arteries, and for PTGIR in part of the luminal epithelium and endothelial cells in a portion of the endometrial arteries. On Day 8, PGI(2) decreased contraction intensity in endometrium/myometrium and myometrium of the saline-treated uteri and increased the contraction intensity in both types of strips from the inflamed organs. Our study reveals that inflammation of the porcine uterus upregulates PGI(2) synthesis and that PGI(2) increases contractility, which suggests that PGI(2) might be essential for the course of uterine inflammation., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The objectives of this study were to assess the clinical and metabolic risk factors for clinical endometritis, the likelihood for having a normal vaginal discharge during postpartum, and the effects of endometritis on milk yield, reproductive efficiency, and metabolic status in Holstein cows. The study was conducted in a commercial dairy herd (Cordoba, Argentina) where 303 Holstein cows were enrolled. Cows were body condition scored (1 to 5) and tail bled on -14, 7, 21, 31, 41, and 50 d relative to parturition. Cows having a vaginal discharge with presence of pus between 21 and 41 d postpartum (dpp) were diagnosed as having clinical endometritis. Plasma blood samples were analyzed for nonesterified fatty acids (NEFA), β-hydroxybutyrate (BHBA), and blood urea nitrogen using commercial kits and insulin-like growth factor 1, insulin, and leptin by RIA. Data were analyzed with PROC MIXED, PROC GENMOD, and PROC PHREG of SAS (SAS Institute Inc., Cary, NC). Abnormal calving and puerperal metritis increased the risk for endometritis [adjusted odds ratio (AOR)=2.21 for both]. High prepartum NEFA and high postpartum BHBA increased the risk for endometritis (AOR=1.003 and 1.001, respectively), whereas high prepartum blood urea nitrogen reduced it (AOR=0.853). Cut-offs of 456.6 μM NEFA and 402.5 μM BHBA had sensitivities of 0.69 and 0.58, and specificities of 0.88 and 0.86, respectively. The likelihood for having normal vaginal discharge increased with time (∼1% × dpp) and with normal calving. Cows with endometritis had higher milk yield than normal herdmates (27.8±0.9 vs. 25.7±0.4 kg/d), lower risk for pregnancy by 100 dpp (AOR=0.10), higher nonpregnancy risk by 200 dpp (AOR=2.87), and higher risk for culling than normal cows (AOR=2.28). Cows with endometritis had a lower hazard rate (0.44) for pregnancy and had approximately 70 d longer calving-to-conception intervals. Finally, endometritis had no effect on metabolic hormones. In conclusion, the risk for clinical endometritis increases with abnormal calving and puerperal metritis, as prepartum NEFA and postpartum BHBA concentrations increase. Prepartum NEFA and postpartum BHBA could be useful for the prediction of endometritis. Last, clinical endometritis has detrimental effects on reproductive efficiency, as affected cows take longer to get pregnant and are at higher risk for culling., (Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the impact of cytologically determined endometritis (CE) diagnosed according to three different cytological thresholds in the 4th and 6th week postpartum (p. p.) on the subsequent reproductive performance in dairy cows., Material and Methods: Dairy cows (n = 222) were clinically examined in the 4th week (Exam I) and in the 6th week (Exam II) p. p. and endometrium samples were collected for cytological examination using the cytobrush method. Three cytological thresholds (percent of polymorphonuclear leucocytes to epithelial cells) were used for categorization of cows: 1) > 18% at Exam I and > 10% at Exam II; 2) > 8% at Exams I and II; 3) > 5% at Exams I and II. The animals were categorized as endometritis positive (CE+) or negative (CE-) according to all cytological thresholds at Exams I and II. For all six experimental groups the following reproductive parameters were calculated: first insemination pregnancy rate, number of services per conception, intercalving period, and total pregnancy rate on day 300 p. p., Results: According to different thresholds prevalence of CE ranged from 48.0% to 65.9% at Exam I and from 26.0% to 34.7% at Exam II. The first insemination pregnancy rate was statistically lower in all CE positive groups at Exam I. Number of inseminations per conception was higher (p < 0.05) in each CE positive cows with exception of group CE+ at Exam II. Intercalving periods were longer in CE cows, and significant (p < 0.05) difference was found for groups ICE+ and ICE- at Exam I. Overall pregnancy rates were similar in cytologically determined endometritis and control cows., Conclusion and Clinical Relevance: Impaired fertility at herd level may concern only particular reproductive indices. It seems that each herd with subclinical endometritis needs to be evaluated and managed individually, according to the different housing, feeding, and environmental conditions. The first of three thresholds used to cytologically diagnose endometritis seems to be the most reliable when applied in the 4th week p. p.