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The uterine environment provides necessary conditions for the existence of endometrial microbiota, which in turn plays an important role in maintaining the homeostasis of the uterine environment. The endometrial microbiome is highly susceptible to external factors such as age, hormones, menstrual, pregnancy, etc. When the microbiota is imbalanced, it will further promote the occurrence of uterine diseases such as endometritis and endometrial cancer. Regulating the microbiome of the endometrium is of positive significance for promoting uterine health. Among them, antibiotics, probiotics, prebiotics, and microbial transplantation may be important pathways for regulating endometrial microbiota in the future. However, there is currently no unified plan for evaluating the endometrial microbiota. In addition, due to the small sample size, it is easy to be contaminated by exogenous bacterial DNA, which poses great challenges for studying the mechanism of microbial community regulating uterine health. Therefore, there are still many areas worth exploring for the future of endometrial microbiome. [ABSTRACT FROM AUTHOR]

Simple Summary: Donkeys play crucial roles in agriculture and human livelihoods globally. Reproductive disorders in donkeys pose significant challenges to their health and well-being. While donkeys share many similarities with horses, specific aspects of donkey disorders remain poorly understood. Knowledge about reproductive disorders of donkeys is important for accurate diagnosis and effective treatment for these animals. This review aims to provide a brief update on reproductive disorders of donkeys including common infectious and non-infectious causes for infertility and pregnancy loss. Understanding reproductive health in donkeys plays a crucial role in enhancing the welfare status of donkeys and decreasing associated economic loss. Reproductive disorders in donkeys present a significant challenge to their health and welfare, impacting their roles in agriculture, conservation, and companionship. With the development of large-scale donkey farming in recent years, reproductive disorders have become a limiting factor for the expansion of the donkey population. In general, donkeys suffer from a similar array of diseases like horses, but little is known about the specificities of donkey reproductive disorders. This review synthesizes current knowledge on the pathogenesis, distribution, presentation, diagnosis, treatment, and prognosis of a diverse array of reproductive disorders affecting donkeys. There are similar infectious and non-infectious causes for infertility and pregnancy loss in jennies compared with mares, but a difference in disease susceptibility does exist, which may be attributed to genetic influence, pathogen specificity, the environment, and reproductive management practices. Diagnostic and treatment plans need to be tailored towards the particularities of donkey reproductive disorders to increase donkey populations and to enhance the standard of care for this species. Enhancing reproductive health in donkeys not only ensures their sustainable use but also promotes their welfare and longevity in diverse human–animal interactions. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. The objective was to assess differences in productive and reproductive performance, and survival associated with vaginal discharge characteristics and fever in postpartum dairy cows located in western and southern states of the United States. This retrospective cohort study included data from 3 experiments conducted in 9 dairies. Vaginal discharge was evaluated twice within 12 DIM and scored on a 5-point scale. The highest vaginal discharge score observed for each cow was used to allocate them into 1 of 5 possible groups (VD group) as follows: VD 1 and 2 (VD 1/2; n = 1,174) = clear mucus or lochia with or without flecks of pus; VD 3 (n = 1,802) = mucopurulent with <50% pus; VD 4 (n = 1,643) = mucopurulent with ≥50% of pus or nonfetid reddish-brownish mucus, n = 1,643; VD 5 = fetid, watery, and reddish-brownish, n = 1,800. All VD 5 cows received treatment according to each herd's protocol. Rectal temperature was assessed in a subset of VD 5 cows, and subsequently divided into fever (rectal temperature ≥39.5°C; n = 334) and no fever (n = 558) groups. A smaller proportion of cows with VD 5 (67.6%) resumed ovarian cyclicity compared with VD 1/2 (76.2%) and VD 4 (72.9%) cows; however, a similar proportion of VD 5 and VD 3 (72.6%) cows resumed ovarian cyclicity. A smaller proportion of VD 5 (85.8%) cows received at least one AI compared with VD 1/2 (91.5%), VD 3 (91.0%), or VD 4 (91.6%) cows. Although we did not detect differences in pregnancy at first AI according to VD, fewer cows with VD 5 (64.4%) were pregnant at 300 DIM than cows with VD 1/2 (76.5%), VD 3 (76.2%), or VD 4 (74.7%). Hazard of pregnancy by 300 DIM was smaller for VD 5 compared with VD 1/2, VD 3, or VD 4 cows. A greater proportion of VD 5 cows were removed from the herd within 300 DIM compared with other VD groups. Milk production was 760 kg lower within 300 DIM for VD 5 compared with VD 2, VD 3, and VD 4, whereas VD 2, VD 3, and VD 4 had similar milk production. We did not detect an association between fever at diagnosis of VD 5 and reproductive performance or milk production. A greater proportion of VD 5 cows without fever were removed from the herd by 300 DIM compared with VD 5 cows with fever. Differences in productive and reproductive performance, and removal of the herd were restricted to fetid, watery, and reddish-brownish vaginal discharge, which was independent of fever. [ABSTRACT FROM AUTHOR]

Background: Thomas Cullen described bleeding abnormalities and dysmenorrhea as the "expected" presentations of adenomyomas. Adenomyosis is included within the FIGO classification of structural causes of abnormal uterine bleeding (AUB). Nevertheless, this long-standing association has been questioned by some authors who reported a high incidence of adenomyosis in uteri removed for indications other than AUB or dysmenorrhea. Here, we examine evidence for the link between adenomyosis and AUB. Methods: A comprehensive Medline literature review of all publications to October 2023. Results: Sixty-three articles were identified and included in the review. Despite a large body of studies, the available literature does not provide conclusive evidence of a link between adenomyosis and AUB. This is because of unsuitable study design, or poor characterization of the study population or of the inclusion or exclusion criteria. Additional challenges arise because of the lack of agreed criteria for diagnosing adenomyosis and the often absence of detailed assessment of menstrual blood loss. Adenomyosis often coexists with other conditions that have also been linked to similar symptoms, and many cases of adenomyosis are asymptomatic. Conclusion: Most of the existing literature and studies that addressed treatment outcome of adenomyosis started from the premise that a link between the condition and AUB had been proven. Yet, published information shows that aspects such a relationship is still uncertain. Further research is needed to address the relation between AUB and adenomyosis burden (or subtypes), distribution, and concomitant pathology. [ABSTRACT FROM AUTHOR]

Abstract Background Metritis is a prevalent uterine disease that affects the welfare, fertility, and survival of dairy cows. The uterine microbiome from cows that develop metritis and those that remain healthy do not differ from calving until 2 days postpartum, after which there is a dysbiosis of the uterine microbiome characterized by a shift towards opportunistic pathogens such as Fusobacteriota and Bacteroidota. Whether these opportunistic pathogens proliferate and overtake the uterine commensals could be determined by the type of substrates present in the uterus. The objective of this study was to integrate uterine microbiome and metabolome data to advance the understanding of the uterine environment in dairy cows that develop metritis. Holstein cows (n = 104) had uterine fluid collected at calving and at the day of metritis diagnosis. Cows with metritis (n = 52) were paired with cows without metritis (n = 52) based on days after calving. First, the uterine microbiome and metabolome were evaluated individually, and then integrated using network analyses. Results The uterine microbiome did not differ at calving but differed on the day of metritis diagnosis between cows with and without metritis. The uterine metabolome differed both at calving and on the day of metritis diagnosis between cows that did and did not develop metritis. Omics integration was performed between 6 significant bacteria genera and 153 significant metabolites on the day of metritis diagnosis. Integration was not performed at calving because there were no significant differences in the uterine microbiome. A total of 3 bacteria genera (i.e. Fusobacterium, Porphyromonas, and Bacteroides) were strongly correlated with 49 metabolites on the day of metritis diagnosis. Seven of the significant metabolites at calving were among the 49 metabolites strongly correlated with opportunistic pathogenic bacteria on the day of metritis diagnosis. The main metabolites have been associated with attenuation of biofilm formation by commensal bacteria, opportunistic pathogenic bacteria overgrowth, tissue damage and inflammation, immune evasion, and immune dysregulation. Conclusions The data integration presented herein helps advance the understanding of the uterine environment in dairy cows with metritis. The identified metabolites may provide a competitive advantage to the main uterine pathogens Fusobacterium, Porphyromonas and Bacteroides, and may be promising targets for future interventions aiming to reduce opportunistic pathogenic bacteria growth in the uterus.

In an 8-year period at two medical center, 138 patients underwent uterine artery embolization, and 11 of them were diagnosed with uterine necrosis. Among them, three were successfully conceived. However, one of them developed an arteriovenous malformation after an artificial abortion, and another experienced complications, including placenta previa and placenta accreta spectrum, which resulted in early preterm delivery and recurrent postpartum hemorrhage, necessitating subtotal hysterectomy. Therefore, it is crucial to prepare for potential adverse pregnancy outcomes in subsequent pregnancies for patients with a history of uterine necrosis.

Background: Metritis is a prevalent uterine disease that affects the welfare, fertility, and survival of dairy cows. The uterine microbiome from cows that develop metritis and those that remain healthy do not differ from calving until 2 days postpartum, after which there is a dysbiosis of the uterine microbiome characterized by a shift towards opportunistic pathogens such as Fusobacteriota and Bacteroidota. Whether these opportunistic pathogens proliferate and overtake the uterine commensals could be determined by the type of substrates present in the uterus. The objective of this study was to integrate uterine microbiome and metabolome data to advance the understanding of the uterine environment in dairy cows that develop metritis. Holstein cows (n = 104) had uterine fluid collected at calving and at the day of metritis diagnosis. Cows with metritis (n = 52) were paired with cows without metritis (n = 52) based on days after calving. First, the uterine microbiome and metabolome were evaluated individually, and then integrated using network analyses. Results: The uterine microbiome did not differ at calving but differed on the day of metritis diagnosis between cows with and without metritis. The uterine metabolome differed both at calving and on the day of metritis diagnosis between cows that did and did not develop metritis. Omics integration was performed between 6 significant bacteria genera and 153 significant metabolites on the day of metritis diagnosis. Integration was not performed at calving because there were no significant differences in the uterine microbiome. A total of 3 bacteria genera (i.e. Fusobacterium, Porphyromonas, and Bacteroides) were strongly correlated with 49 metabolites on the day of metritis diagnosis. Seven of the significant metabolites at calving were among the 49 metabolites strongly correlated with opportunistic pathogenic bacteria on the day of metritis diagnosis. The main metabolites have been associated with attenuation of biofilm formation by commensal bacteria, opportunistic pathogenic bacteria overgrowth, tissue damage and inflammation, immune evasion, and immune dysregulation. Conclusions: The data integration presented herein helps advance the understanding of the uterine environment in dairy cows with metritis. The identified metabolites may provide a competitive advantage to the main uterine pathogens Fusobacterium, Porphyromonas and Bacteroides, and may be promising targets for future interventions aiming to reduce opportunistic pathogenic bacteria growth in the uterus. [ABSTRACT FROM AUTHOR]

Simple Summary: Uterine health is crucial for cows to become pregnant and maintain farm profitability. However, when cows suffer from uterine diseases, it not only affects their fertility but also leads to increased antibiotic usage, impacting both animal health and farm economics. Probiotics, which are beneficial bacteria, offer a promising solution to improve cow health and reproductive success. Research suggests that certain probiotics can enhance cow fertility. Administering these probiotics directly into the cow's vagina may strengthen uterine health, especially after giving birth. While initial findings are promising, further large-scale studies are needed to confirm their effectiveness. This paper underscores the importance of establishing clear guidelines for using probiotics in cow management, including selecting appropriate strains and administering them correctly. Moving forward, continued research is necessary to fully understand the benefits of probiotics in maintaining cow health and improving fertility. Uterine disease in cattle impairs reproductive performance and profitability and increases antibiotic use and antimicrobial resistance. Thus, probiotics offer a promising alternative therapy. This review presents conceptual findings on the efficacy of probiotics in managing uterine diseases and fertility in cows. Probiotics containing Lactobacillus spp. and Bifidobacterium spp. individually or as composite formulations are known to improve fertility. Strategic intravaginal administration of these formulations would likely enhance uterine immunity, particularly during the postpartum period. While current findings on the benefits to uterine health are encouraging, there is still significant knowledge missing, including a lack of empirical information from large-scale field trials. This review underscores the need for evidence-based guidelines for probiotics, such as genomic selection of formulations, targeted delivery, or potential synergy with other interventions. Future research should address these gaps to maximize the potential of probiotics in managing uterine diseases and enhancing the reproductive health of dairy cattle. [ABSTRACT FROM AUTHOR]

Up to 50 % of dairy cows fail to resolve uterine involution and develop chronic clinical (CE) or subclinical endometritis (SE) 21 days after calving. Clinical endometritis is associated with purulent discharge, while SE is not associated with overt clinical signs. Along with numerous knowledge gaps related to its pathogenesis, SE does not allow for a straightforward and effective therapy. Therefore, it is crucial to unravel differences in the expression of genes among healthy, CE, and SE cows. This might contribute to the discovery of new drug candidates and, in consequence, a potentially effective treatment. In the present study, cows between 21 and 28 days postpartum (PP) were examined using vaginoscopy for the presence of vaginal discharge and endometrial cytology for the determination of the endometrial polymorphonuclear cell (PMN) percentage. Next, an endometrial biopsy sample was taken to investigate the expression of 13 selected candidate genes by qPCR. Uterine health status was assigned to healthy (absence of abnormal vaginal discharge and ≤5 % PMN, n = 13), SE (absence of abnormal vaginal discharge and >5 % PMN, n = 30), and CE (mucopurulent or purulent vaginal discharge and >5 % PMN, n = 9). At the same time, a blood sample was collected to assess serum progesterone concentration and to categorize cows as low (≤1 ng/mL) or high (>1 ng/mL) in progesterone. High expression of IL1B, IL6, IL17A, CXCL8, PTGES, PTGS1, PTGS2, and INHBA genes and low expression of FST was noted in the endometrium of CE compared to healthy cows. Increased endometrial INHBA expression was observed in both SE and CE compared to healthy cows. Interestingly, greater expression of PTGES and PRXL2B genes and lower expression of PTGS2 were characteristic of SE versus CE or healthy. Among cows with no overt clinical symptoms of uterine disease (healthy and SE), the endometrial expression of IL1 B, CXCL8, and PTGES was greater in cows with high versus low serum progesterone. Several genes were differentially expressed among healthy, SE, and CE cows indicating different pathways for the development of different uterine diseases. In conclusion, we found progesterone-independent SE markers, which suggests that low endometrial PTGS2 expression may be indicative of an inadequate immune response and thus contribute to the pathogenesis of SE. • Progesterone concentration did not affect mRNA expression of INHBA, FST, or INHA. • INHBA, POSTN, and FST may play significant roles in endometrial inflammation. • Cytokine expression (IL1B, IL6, IL17A, CXCL8) was upregulated in cows with CE compared to SE. [ABSTRACT FROM AUTHOR]

Reproductive disorders in donkeys present a significant challenge to their health and welfare, impacting their roles in agriculture, conservation, and companionship. With the development of large-scale donkey farming in recent years, reproductive disorders have become a limiting factor for the expansion of the donkey population. In general, donkeys suffer from a similar array of diseases like horses, but little is known about the specificities of donkey reproductive disorders. This review synthesizes current knowledge on the pathogenesis, distribution, presentation, diagnosis, treatment, and prognosis of a diverse array of reproductive disorders affecting donkeys. There are similar infectious and non-infectious causes for infertility and pregnancy loss in jennies compared with mares, but a difference in disease susceptibility does exist, which may be attributed to genetic influence, pathogen specificity, the environment, and reproductive management practices. Diagnostic and treatment plans need to be tailored towards the particularities of donkey reproductive disorders to increase donkey populations and to enhance the standard of care for this species. Enhancing reproductive health in donkeys not only ensures their sustainable use but also promotes their welfare and longevity in diverse human–animal interactions.

Abstract Background Helcococcus ovis (H. ovis) is an emerging bacterial pathogen that commonly causes opportunistic respiratory, mammary, and uterine infections across mammalian hosts. This study applied long- and short-read whole genome sequencing technologies to identify virulence factors in five H. ovis isolates with low, medium, and high virulence phenotypes. Results The resulting assemblies contained one circular chromosome ranging from 1,744,566 to 1,850,083 bp in length and had a mean GC content of 27.6%. Phylogenetic and nucleotide identity analyses found low virulence strain KG38 to be part of a clade that forms an outgroup apart from the rest of the H. ovis taxon. Assembling the first complete genomes of the species revealed major genomic rearrangements in KG38. One to six prophage regions were identified in each genome. A novel pathogenicity island was found exclusively in the two high virulence strains (KG37 and KG104), along with two hypothetical transmembrane proteins designated as putative VFs. Finally, three zinc ABC transporters and three Type-II/IV secretion systems were identified as possible virulence determinants in this species. The low virulence strain KG38 has fewer intact paralogs of these operons in its genome compared to the higher virulence isolates, which strongly suggests a role in virulence. This strain is also missing four putative virulence factors (VFs) found in other isolates associated with adherence (collagen adhesin precursor), immune evasion (choline-binding protein A and a PspA-like hypothetical protein) and cell wall synthesis (glycerol-3-phosphate cytidylyltransferase). Conclusions In this study, we assembled reference-quality complete genomes for five H. ovis strains to identify putative virulence factors. Phylogenetic analyses of H. ovis isolates revealed the presence of a clade representing a potentially novel species within the genus Helcococcus. A novel pathogenicity island and two hypothetical transmembrane proteins were found exclusively in high-virulence strains. The identification of Zinc ABC transporters and Type-II/IV secretion systems as possible virulence determinants, along with the differences in operon content between the low and high virulence isolates, strongly suggests they also play a role in the bacterium’s pathogenicity. Taken together, these findings are a valuable first step toward deciphering the pathogenesis of H. ovis infections.

Cesarean scar pregnancy (CSP) is a rare complication that occurs in less than 1% of ectopic pregnancies, and uterine didelphys is one of the rarest uterine forms. We report a successful laparoscopic excision and repair of CSP in a woman with uterine didelphys and a double vagina. A 34-year-old gravida one, para one woman with a history of low transverse cesarean section presented to our hospital with a suspected CSP. She was confirmed to have uterine didelphys with a double vagina during an infertility examination 7 years earlier. Magnetic resonance imaging showed a 2.5-cm gestational sac-like cystic lesion in the lower segment of the right uterus at the cesarean scar. We decided to perform a laparoscopic approach after informing the patient of the surgical procedure. The lower segment of the previous cesarean site was excised with monopolar diathermy to minimize bleeding. We identified the gestational sac in the lower segment of the right uterus, which was evacuated using spoon forceps. The myometrium and serosa of the uterus were sutured layer-by-layer using synthetic absorbable sutures. No remnant gestational tissue was visible on follow-up ultrasonography one month after the surgery. This laparoscopic approach to CSP in a woman with uterine didelphys is an effective and safe method of treatment. In women with uterine anomalies, it is important to confirm the exact location of the gestational sac by preoperative imaging for successful surgery.

Background: Thomas Cullen described bleeding abnormalities and dysmenorrhea as the “expected” presentations of adenomyomas. Adenomyosis is included within the FIGO classification of structural causes of abnormal uterine bleeding (AUB). Nevertheless, this long-standing association has been questioned by some authors who reported a high incidence of adenomyosis in uteri removed for indications other than AUB or dysmenorrhea. Here, we examine evidence for the link between adenomyosis and AUB. Methods: A comprehensive Medline literature review of all publications to October 2023. Results: Sixty-three articles were identified and included in the review. Despite a large body of studies, the available literature does not provide conclusive evidence of a link between adenomyosis and AUB. This is because of unsuitable study design, or poor characterization of the study population or of the inclusion or exclusion criteria. Additional challenges arise because of the lack of agreed criteria for diagnosing adenomyosis and the often absence of detailed assessment of menstrual blood loss. Adenomyosis often coexists with other conditions that have also been linked to similar symptoms, and many cases of adenomyosis are asymptomatic. Conclusion: Most of the existing literature and studies that addressed treatment outcome of adenomyosis started from the premise that a link between the condition and AUB had been proven. Yet, published information shows that aspects such a relationship is still uncertain. Further research is needed to address the relation between AUB and adenomyosis burden (or subtypes), distribution, and concomitant pathology.

Uterine disease in cattle impairs reproductive performance and profitability and increases antibiotic use and antimicrobial resistance. Thus, probiotics offer a promising alternative therapy. This review presents conceptual findings on the efficacy of probiotics in managing uterine diseases and fertility in cows. Probiotics containing Lactobacillus spp. and Bifidobacterium spp. individually or as composite formulations are known to improve fertility. Strategic intravaginal administration of these formulations would likely enhance uterine immunity, particularly during the postpartum period. While current findings on the benefits to uterine health are encouraging, there is still significant knowledge missing, including a lack of empirical information from large-scale field trials. This review underscores the need for evidence-based guidelines for probiotics, such as genomic selection of formulations, targeted delivery, or potential synergy with other interventions. Future research should address these gaps to maximize the potential of probiotics in managing uterine diseases and enhancing the reproductive health of dairy cattle.

Background: Helcococcus ovis (H. ovis) is an emerging bacterial pathogen that commonly causes opportunistic respiratory, mammary, and uterine infections across mammalian hosts. This study applied long- and short-read whole genome sequencing technologies to identify virulence factors in five H. ovis isolates with low, medium, and high virulence phenotypes. Results: The resulting assemblies contained one circular chromosome ranging from 1,744,566 to 1,850,083 bp in length and had a mean GC content of 27.6%. Phylogenetic and nucleotide identity analyses found low virulence strain KG38 to be part of a clade that forms an outgroup apart from the rest of the H. ovis taxon. Assembling the first complete genomes of the species revealed major genomic rearrangements in KG38. One to six prophage regions were identified in each genome. A novel pathogenicity island was found exclusively in the two high virulence strains (KG37 and KG104), along with two hypothetical transmembrane proteins designated as putative VFs. Finally, three zinc ABC transporters and three Type-II/IV secretion systems were identified as possible virulence determinants in this species. The low virulence strain KG38 has fewer intact paralogs of these operons in its genome compared to the higher virulence isolates, which strongly suggests a role in virulence. This strain is also missing four putative virulence factors (VFs) found in other isolates associated with adherence (collagen adhesin precursor), immune evasion (choline-binding protein A and a PspA-like hypothetical protein) and cell wall synthesis (glycerol-3-phosphate cytidylyltransferase). Conclusions: In this study, we assembled reference-quality complete genomes for five H. ovis strains to identify putative virulence factors. Phylogenetic analyses of H. ovis isolates revealed the presence of a clade representing a potentially novel species within the genus Helcococcus. A novel pathogenicity island and two hypothetical transmembrane proteins were found exclusively in high-virulence strains. The identification of Zinc ABC transporters and Type-II/IV secretion systems as possible virulence determinants, along with the differences in operon content between the low and high virulence isolates, strongly suggests they also play a role in the bacterium's pathogenicity. Taken together, these findings are a valuable first step toward deciphering the pathogenesis of H. ovis infections. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to determine the prevalence of pathology confirmed adenomyosis in women with chronic pelvic pain (CPP) who underwent surgical management with total hysterectomy, and to identify associated risk factors and demographic variables. Methods: This is a retrospective cohort study involving 1186 patients treated in a CPP-specialty clinic who underwent surgical management with hysterectomy between January 2010 and December 2021. Results: About 532/1186 (44.9%) of the cohort were diagnosed with adenomyosis on pathology following total hysterectomy. The average age of patients with adenomyosis was older than those without adenomyosis [41 years vs 38 years (p < 0.001)]. There were no statistically significant differences in symptoms of menstrual bleeding, pelvic pain, dysmenorrhea, or dyspareunia. Those with adenomyosis were more likely to be Hispanic (p < 0.001), have a history of pregnancy (p < 0.001), and have chronic cervicitis (p = 0.037). Uterine weight was significantly higher in the group with adenomyosis (p = 0.033) especially when excluding leiomyoma (p = 0.006). Discussion: The prevalence of adenomyosis on surgical pathology in a CPP cohort was higher than that reported for the general population. Uterine weights are higher in adenomyosis, even when controlling for leiomyoma. Classically attributed symptoms of adenomyosis were not useful predictors for the disease. [ABSTRACT FROM AUTHOR]

ABSTRACT: Uterine diseases and heat stress (HS) are major challenges for the dairy cow. Heat stress alters host immune resilience, making cows more susceptible to the development of uterine disease. Although HS increases the incidence of uterine disease, the mechanisms by which this occurs are unclear. We hypothesize that evaporative cooling (CL) to alleviate HS in prepartum cows has carry-over effects on postpartum innate immunity. Nulliparous pregnant Holstein heifers were assigned to receive either forced CL that resulted in cool conditions (shade with water soakers and fans; n = 14) or to remain under HS conditions (barn shade only; n = 16) for 60 d prepartum. Postpartum, all cows were housed in a freestall barn equipped with shade, water soakers, and fans. Respiratory rate and rectal temperature during the prepartum period were greater in HS heifers compared with CL heifers, indicative of HS. Although milk production was decreased in HS cows compared with CL cows, the incidence of uterine disease and content of total or pathogenic bacteria in vaginal mucus on d 7 or d 21 postpartum was not affected by treatment. Whole blood was collected on d 21 and subjected to in vitro stimulation with lipopolysaccharide. Lipopolysaccharide-induced accumulation of IL-1β, IL-10, and MIP-1α was greater in blood collected from HS cows compared with CL cows. Our results imply that prepartum HS during late pregnancy has carry-over effects on postpartum innate immunity, which may contribute to the increased incidence of uterine disease observed in cows exposed to prepartum HS.

We aimed to compare the viability of circulating polymorphonuclear leukocyte (cPMN) and endometrial PMN (ePMN) and their function dynamics in postpartum dairy cows with subclinical (SCE) or clinical endometritis (CE). To do so, blood samples from 38 Holstein cows were collected at −7, 9, 21, and 36 d relative to calving, and endometrial cytology samples from 32 Holstein cows were harvested at 9, 21, and 36 d postpartum. Uterine health status was assessed at 36 d postpartum, and cows were classified as healthy (absence of abnormal vaginal discharge and ≤5% ePMN), SCE (absence of abnormal vaginal discharge and >5% ePMN), or CE (mucopurulent or purulent vaginal discharge and >5% ePMN). Viability (viable, apoptotic, and necrotic) and function parameters phagocytosis (PC), oxidative burst, and intracellular proteolytic degradation were evaluated for cPMN via flow cytometry. For ePMN, only viability and PC were evaluated. The association of cPMN and ePMN viability and functional parameters with reproductive tract health classification were fitted in mixed linear regression models, accounting for repeated measures, sampling day, and interactions of reproductive tract status and day. Cows with CE had a lower proportion of cPMN viability (84.5 ± 2.1%; least squares means ± standard error) and a higher proportion of apoptosis (14.4 ± 2.0%) than healthy (92.4 ± 1.3 and 6.7 ± 1.3%, respectively) or SCE (95.3 ± 2.4 and 3.8 ± 2.3%, respectively) at 9 d postpartum. Interestingly, cPMN intracellular proteolytic degradation was lower [6.2 ± 0.1 median fluorescence intensity (MFI)] in SCE compared with healthy (6.7 ± 0.08 MFI) or CE (6.8 ± 0.1 MFI) at d 9 postpartum. No other differences in cPMN function were found among experimental groups. The proportion of necrotic ePMN was higher for healthy (49.6 ± 5.1%) than SCE (27.4 ± 7.3%) and CE (27.7 ± 7.3%) cows at 36 d postpartum. Also, at 36 d postpartum, the proportion of ePMN performing PC was higher in CE (47.0 ± 8.6%) than in healthy (18.4 ± 7.6%) cows, but did not differ from SCE cows (25.9 ± 8.7%). Results of the present study suggest that cPMN viability and function at 9 d postpartum are associated with the development of uterine disease. Furthermore, ePMN at 36 d postpartum are mostly necrotic in healthy cows but viable and functional in cows with CE, probably due to active uterine inflammation. Remarkably, ePMN in cows with SCE at 36 d postpartum are also mostly viable but seem to display a numerically lower proportion of PC compared with ePMN in CE cows. [ABSTRACT FROM AUTHOR]

Objectives were to evaluate differences in the uterine and serum metabolomes associated with metritis in dairy cows. Vaginal discharge was evaluated using a Metricheck device (Simcro) at 5, 7, and 11 d in milk (DIM; herd 1) or 4, 6, 8, 10, and 12 DIM (herd 2). Cows with reddish or brownish, watery, and fetid discharge were diagnosed with metritis (n = 24). Cows with metritis were paired with herdmates without metritis (i.e., clear mucous vaginal discharge or clear lochia with ≤50% of pus) based on DIM and parity (n = 24). Day of metritis diagnosis was considered study d 0. All cows diagnosed with metritis received antimicrobial therapy. The metabolome of uterine lavage collected on d 0 and 5, and serum samples collected on d 0 were evaluated using untargeted gas chromatography time-of-flight mass spectrometry. Normalized data were subjected to multivariate canonical analysis of population using the MultBiplotR and MixOmics packages in R Studio. Univariate analyses including t -test, principal component analyses, partial least squares discriminant analyses, and pathway analyses were conducted using Metaboanalyst. The uterine metabolome differed between cows with and without metritis on d 0. Differences in the uterine metabolome associated with metritis on d 0 were related to the metabolism of butanoate, amino acids (i.e., glycine, serine, threonine, alanine, aspartate, and glutamate), glycolysis and gluconeogenesis, and the tricarboxylic acid cycle. No differences in the serum metabolome were observed between cows diagnosed with metritis and counterparts without metritis on d 0. Similarly, no differences in uterine metabolome were observed between cows with metritis and counterparts not diagnosed with metritis on d 5. These results indicate that the establishment of metritis in dairy cows is associated with local disturbances in amino acid, lipid, and carbohydrate metabolism in the uterus. The lack of differences in the uterine metabolome on d 5 indicates that processes implicated with the disease are reestablished by d 5 after diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Dairy cows diagnosed with metritis may experience a greater degree of oxidative stress (OS) and a deficit in the antioxidative capacity compared to healthy cows. We aimed to assess circulating OS markers and endometrial cell mitochondrial function, intracellular reactive oxygen species (ROS) production, and mean endometrial nuclear cell area in postpartum cows diagnosed with metritis or as healthy. From an initial pool of 121 Holstein cows, we retrospectively selected 34 cows and balanced for metritis (n = 17) or healthy (n = 17). Metritis was defined as an enlarged uterus with red-brown watery or thick off-white purulent discharge occurring within 21 days postpartum. Cows with no signs of clinical disease (including dystocia or retained placenta) were referred to as healthy. Blood samples for serum reactive oxygen metabolites (d-ROM), antioxidants (OXY), and oxidative status index (OSI) tests, evaluated via photometric determination of plasma thiols, were performed at 7, 14, 21, 28, and 35 days postpartum. Furthermore, from the initial pool, a random subset of 5 cows diagnosed with metritis and 6 diagnosed as healthy we collected (at the same time points as for the blood samples) endometrial cytology samples using the cytobrush technique. From the uterine samples, we evaluated the endometrial cell mitochondrial function, intracellular ROS levels, and the endometrial cell nuclear area using MitoTracker Orange, dichlorodihydrofluorescein diacetate, and Hoechst 33258, respectively. Mixed linear regression models, accounting for repeated measurements, were fitted to assess the effect of metritis versus healthy on circulating and endometrial cell OS parameters and endometrial cell size. The effect of days postpartum and its interaction with uterine health status were forced into each model. Serum concentrations of d-ROMs and OSI were greater in metritis at 7, 14, and 35 days postpartum than in healthy cows. Interestingly, the mean endometrial cell nuclear area was lower in metritis than healthy cows at 14 and 21 days postpartum. We found no differences between metritis and healthy for endometrial cell mitochondrial function and intracellular ROS production. In conclusion, cows diagnosed with metritis experienced greater systemic OS levels than healthy cows, but their OS was not higher in the uterine milieu. • Cows diagnosed with metritis experience greater systemic levels of oxidative stress than healthy cows. • Endometrial mitochondrial function or intracellular ROS did not differ between healthy and metritis cows. • Oxidative stress serum markers can be used as a management tool to monitor the early stages of metritis. [ABSTRACT FROM AUTHOR]

Uterine diseases and heat stress (HS) are major challenges for the dairy cow. Heat stress alters host immune resilience, making cows more susceptible to the development of uterine disease. Although HS increases the incidence of uterine disease, the mechanisms by which this occurs are unclear. We hypothesize that evaporative cooling (CL) to alleviate HS in prepartum cows has carry-over effects on postpartum innate immunity. Nulliparous pregnant Holstein heifers were assigned to receive either forced CL that resulted in cool conditions (shade with water soakers and fans; n = 14) or to remain under HS conditions (barn shade only; n = 16) for 60 d prepartum. Postpartum, all cows were housed in a freestall barn equipped with shade, water soakers, and fans. Respiratory rate and rectal temperature during the prepartum period were greater in HS heifers compared with CL heifers, indicative of HS. Although milk production was decreased in HS cows compared with CL cows, the incidence of uterine disease and content of total or pathogenic bacteria in vaginal mucus on d 7 or d 21 postpartum was not affected by treatment. Whole blood was collected on d 21 and subjected to in vitro stimulation with lipopolysaccharide. Lipopolysaccharide-induced accumulation of IL-1β, IL-10, and MIP-1α was greater in blood collected from HS cows compared with CL cows. Our results imply that prepartum HS during late pregnancy has carry-over effects on postpartum innate immunity, which may contribute to the increased incidence of uterine disease observed in cows exposed to prepartum HS. [Display omitted] [ABSTRACT FROM AUTHOR]

Simple Summary: To analyze miRNA changes for female reproductive aging and organs with uteropathy in dogs, the miRNA expressions of female reproductive organs were compared and validated with real-time PCR. While aging is associated with microRNA (miRNA) expression, little is known about its role in the aging of dog reproductive organs. We examined miRNA expression in ovaries, oviducts, and uteri from young and old dogs and dogs with uteropathy to elucidate miRNA's role in aging. The ovaries, oviducts, and uteri of 18 dogs (Canis familiaris)—young (8.5 ± 1.9 months old), old (78.2 ± 29.0 months old), and those with uteropathy (104.4 ± 15.1 months old)—were collected for miRNA expression examination. Total RNA samples were extracted, reverse-transcribed to cDNA, and real-time PCR analysis was also performed. In ovaries, miR-708 and miR-151 levels were significantly higher in old dogs than in young dogs, and only let-7a, let-7b, let-7c, miR125b, and miR26a were significantly upregulated in dogs with uteropathy. In the oviducts and uteri of old dogs, miR-140, miR-30d, miR-23a, miR-10a, miR-125a, miR-221, and miR-29a were upregulated. Realtime quantitative PCR revealed that targeted mRNA was similarly regulated to miRNA. These results suggest that miRNAs of reproductive organs in dogs may be biological markers for aging and reproductive diseases and could be used for mediating aging. [ABSTRACT FROM AUTHOR]

Heat stress and uterine diseases, including metritis and endometritis, both reduce milk yields and reduce reproductive performance. Bacterial growth is promoted by elevated temperature while heat stress reduces host immune cell function, but it is not known whether increased environmental temperature promotes uterine disease by altering host immunity or bacterial growth. We hypothesize that seasonal variations in environmental temperature influence metritis incidence in the dairy cow independent of bacterial prevalence in the reproductive tract. To investigate how environmental temperature may impact metritis incidence, records of 3507 calvings in Florida over a 5-year period were evaluated. The incidence of metritis increased from 21.1% in the cool season (October through March) to 24.2% during the warm season (April through September, P < 0.05). To elucidate a link between environmental temperature and uterine disease, 102 cows were enrolled during the warm season (September 2017; n = 51) and cool season (February–March 2018; n = 51). Cows were maintained on pasture during the dry period and moved to free stall barns with fans and water soakers immediately prior to calving and remained in that environment after calving. Vaginal mucus was collected and scored on days 7 (to evaluate metritis) and 21 (to evaluate endometritis) postpartum to evaluate the incidence of uterine disease and quantify bacterial content and species using qPCR. Daily milk yield for the first 60 DIM was reduced during the warm season compared with the cool season (32.6 ± 1.62 vs 37.23 ± 1.60 kg, P < 0.05) consistent with effects of prepartum heat stress. Interestingly, more cows had persistent uterine disease on both d 7 and d 21 in the warm season compared with the cool season (58.0 vs 29.4%, P < 0.05). Regardless of calving season the total bacterial content in the vagina was greater on d 7 compared to d 21. While metritis incidence was increased in the warm season, the vaginal content of total bacteria, Escherichia coli , Trueperella pyogenes , Fusobacterium necrophorum and Prevotella melaninogenica were similar during the cool season and the warm season. Our data suggests that prepartum heat stress related to season of calving increased the incidence of metritis and persistence of uterine disease in the dairy cow independent of vaginal bacteria content. The possibility that prepartum heat stress perturbs host immune function and increases the risk of metritis when cows are exposed to an equivalent number of pathogenic bacteria requires further investigation. • Metritis occurs in up to 40% of dairy cows after calving and reduces fertility. • Elevated temperature can increase bacterial growth and impair immune function. • Calving in the summer increased the incidence and persistence of metritis. • Increased metritis in the summer is not associated with increased bacterial load in the vagina. • Findings imply that heat stress impacts host factors that increase the incidence of metritis. [ABSTRACT FROM AUTHOR]

Postpartum uterine disease in dairy cows affects ovarian function, but it is unclear how the type and timing of disease relates to ovarian function. To explore associations between uterine disease and contemporaneous ovarian function, postpartum uterine health was evaluated in 17 lactating primiparous Holstein cows that ovulated. Ovarian function was assessed by measuring daily hormone concentrations and the diameter of the largest follicle and subsequent corpus luteum. Metritis (≤14 d postpartum) was associated with reduced follicle diameter (P = 0.002) and tended to reduce plasma estradiol concentrations (P = 0.062) from d 7 to 16 postpartum compared to cows without metritis. Metritis was associated with reduced plasma progesterone (P = 0.026) but not corpus luteum diameter from d 17 to 26 postpartum. Endometritis (≥15 d postpartum) was associated with reduced corpus luteum diameter (P = 0.005) but did not alter plasma progesterone from d 17 to 26 postpartum compared to cows without endometritis. To explore longer term effects of uterine infection on luteal function, non-lactating primiparous Holstein cows received an intrauterine infusion of vehicle control (n = 11) or pathogenic Escherichia coli and Trueperella pyogenes to induce endometritis (n = 12) and corpora lutea were recovered on d 16 of the estrous cycle, 146 d after intrauterine infusion. Intrauterine infusion of bacteria had no effect on plasma progesterone or luteal diameter compared to control, and only altered the expression of 2 of 94 candidate genes (NCF1 and TLR9). Taken together, these studies imply that uterine diseases are principally associated with changes to ovarian function at a time contemporaneous with disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: The primary aim of this study was to describe the ultrasound features of various endometrial and other intracavitary pathologies in women without abnormal uterine bleeding (AUB) using the International Endometrial Tumor Analysis (IETA) terminology. The secondary aim was to compare our findings with published data on women with AUB.Methods: This was a prospective observational study of women presenting at one of seven centers specialized in gynecological ultrasonography, from 2011 until 2018, for indications unrelated to AUB. All patients underwent transvaginal ultrasound using the IETA examination and measurement techniques. Ultrasonography was performed as part of routine gynecological examination or follow-up of non-endometrial pathology, or as part of the work-up before undergoing treatment for infertility, uterine prolapse or ovarian pathology. Ultrasound findings were described using the IETA terminology. Endometrial sampling was performed after the ultrasound scan. The histological endpoints were endometrial atrophy, proliferative or secretory endometrium, endometrial hyperplasia without atypia, endometrial polyp, intracavitary leiomyoma, endometrial intraepithelial neoplasia (EIN), endometrial cancer (EC) and insufficient tissue. The findings in our cohort of women without AUB were compared with those in a published cohort of women with AUB who were examined with transvaginal ultrasound between 2012 and 2015 using the same IETA examination technique and terminology.Results: In this study (IETA3), we included 1745 women without AUB who underwent a standardized transvaginal ultrasound examination followed by either endometrial sampling with histological diagnosis (n = 1537) or at least 1 year of clinical and ultrasound follow-up (n = 208). Of these, 858 (49.2%) women were premenopausal and 887 (50.8%) were postmenopausal. Histology showed the presence of EC and/or EIN in 29 (1.7%) women, endometrial polyps in 1028 (58.9%), intracavitary myomas in 66 (3.8%), proliferative or secretory changes or hyperplasia without atypia in 144 (8.3%), endometrial atrophy in 265 (15.2%) and insufficient tissue in five (0.3%). Most cases of EC or EIN (25/29 (86.2%)) were diagnosed after menopause. The mean endometrial thickness in women with EC or EIN was 11.2 mm (95% CI, 8.9-13.6 mm), being on average 2.4 mm (95% CI, 0.3-4.6 mm) thicker than their benign counterparts. Women with malignant endometrial pathology manifested more frequently non-uniform echogenicity (22/29 (75.9%)) than did those with benign endometrial pathology (929/1716 (54.1%)) (difference, +21.8% (95% CI, +4.2% to +39.2%)). Moderate to abundant vascularization (color score 3-4) was seen in 31.0% (9/29) of cases with EC or EIN compared with 12.8% (220/1716) of those with a benign outcome (difference, +18.2% (95% CI, -0.5% to +36.9%)). Multiple multifocal vessels were recorded in 24.1% (7/29) women with EC or EIN vs 4.0% (68/1716) of those with a benign outcome (difference, +20.2% (95% CI, +4.6% to +35.7%)). A regular endometrial-myometrial junction was seen less frequently in women with EC or EIN (19/29 (65.5%)) vs those with a benign outcome (1412/1716 (82.3%)) (difference, -16.8% (95% CI, -34.2% to +0.6%)). In women with endometrial polyps without AUB, a single dominant vessel was the most frequent vascular pattern (666/1028 (64.8%)). In women with EC, both in those with and those without AUB, the endometrium usually manifested heterogeneous echogenicity, but the endometrium was on average 8.6 mm (95% CI, 5.2-12.0 mm) thinner and less intensely vascularized (color score 3-4: difference, -26.8% (95% CI, -52.2% to -1.3%)) in women without compared to those with AUB. In both pre- and postmenopausal women, asymptomatic endometrial polyps were associated with a thinner endometrium, and they manifested more frequently a bright edge, a regular endometrial-myometrial junction and a single dominant vessel than did polyps in symptomatic women, and they were less intensely vascularized.Conclusions: We describe the typical ultrasound features of EC, polyps and other intracavitary histologies using IETA terminology in women without AUB. Our findings suggest that the presence of asymptomatic polyps or endometrial malignancy may be accompanied by thinner and less intensely vascularized endometria than their symptomatic counterparts. © 2022 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Abstract Background Cystic endometrial hyperplasia-pyometra complex (CEH-P) is one of the most common uteropathies in bitches. In diseases with mild or obscure clinical signs and normal uterine size, a diagnosis based on a clinical assessment might be incorrect. The main aim of the research was to determine the morphological variables accompanying uterine diseases in bitches in microscopic evaluation. Consequently, the obtained results can be used to create a new classification system for uterine pathological changes during the development of the CEH-P, diagnosed by microscopic examination in bitches. Material for the study consisted of the uteri of 120 female dogs, aged 1–16 years, obtained during routine ovariohysterectomies. Macroscopic observation after a longitudinal incision of the uterine horns, allowed a preliminary classification of the uteri into research groups: control group (physiological uteri), and groups GI-III uteri collected form bitches with varying degrees of endometrial pathology. These preliminary classifications were then verified by histological analysis (H&E stain). Results The obtained results made it possible to determine and describe the prevalence (%) of pathological changes characteristic of the analyzed uterine diseases in the examined bitches. Histopathological analyses that were conducted have confirmed preliminary macroscopic evaluation for the control group, group GII (CEH), and group GIII (pyometra). In the uteri of the GI group, a severe congestion of the endometrium has been observed – this is typical of inflammation – which was not confirmed during histopathological examinations. However, these examinations revealed acute endometrial haemorrhage of varying severity. Conclusions Early reproduction disorders in bitches are, in general, not confirmed by clinical signs in the examined animals. The results show that during classification of typical morphological changes in the endometrium over the development of the CEH-P complex in bitches microscopic examinations are required. The obtained results indicate a frequent lack of consistency in the macroscopic assessment and histological analysis of the endometrium, observed in the analyzed uterine diseases, which in most cases is not followed by clinical symptoms. The presented classification of uterine diseases may be useful as a diagnostic tool in reproductive disorders in bitches and in examination in the field of basic research.

In Experiment 1, PBMC were isolated from cows considered healthy or with SCE (n=6/group) on Days 0 (estrus) and 7 (diestrus) of a synchronized estrous cycle. In Experiment 2, on D21 (D0 was defined as the day of Fixed Timed Artificial Insemination (FTAI), cows were evaluated by ultrasonography to assess luteal blood perfusion and PBMC were isolated. On D32, cows were classified into: healthy pregnant (n=7), pregnant with SCE (n=4), healthy non-pregnant (n=8), and non-pregnant with SCE (n=10). Gene expression of ISGs (ISG15, OAS1, MX1 and IFI6) and proinflammatory cytokines (IL1-β, TNF-α and IFN-γ) were determined. Expression of ISG15, MX1, IFI6, TNF-α and IFN-γ did not differ between SCE and healthy cows and between Days 0 and 7. Expression of OAS1 and IL1-β were higher (P=0.02) on Day 7 than Day 0, regardlees of the SCE presence. In Exp.2, ISG15 abundance was 2.5-fold greater (P=0.0008), TNF-α was 2.2-fold greater (P=0.05), and IL1-β tended (P=0.06) to be 2.4-fold higher in pregnant than non-pregnant cows. Luteal blood perfusion was greater (P=0.01) in pregnant animals. In conclusion, OAS1 and IL1-β are transcripts upregulated in PBMC at diestrus, regardless of SCE occurrence. Proinflammatory cytokines are not affected by SCE occurrence, but IL1-β and TNF-α are upregulated in pregnant animals on D21 of pregnancy. ISG15 abundance is a good pregnancy predictor, regardless SCE presence., Competing Interests: Conflicts of interest: The authors have no conflict of interest to declare., (Copyright © The Author(s).)

While aging is associated with microRNA (miRNA) expression, little is known about its role in the aging of dog reproductive organs. We examined miRNA expression in ovaries, oviducts, and uteri from young and old dogs and dogs with uteropathy to elucidate miRNA’s role in aging. The ovaries, oviducts, and uteri of 18 dogs (Canis familiaris)—young (8.5 ± 1.9 months old), old (78.2 ± 29.0 months old), and those with uteropathy (104.4 ± 15.1 months old)—were collected for miRNA expression examination. Total RNA samples were extracted, reverse-transcribed to cDNA, and real-time PCR analysis was also performed. In ovaries, miR-708 and miR-151 levels were significantly higher in old dogs than in young dogs, and only let-7a, let-7b, let-7c, miR125b, and miR26a were significantly upregulated in dogs with uteropathy. In the oviducts and uteri of old dogs, miR-140, miR-30d, miR-23a, miR-10a, miR-125a, miR-221, and miR-29a were upregulated. Realtime quantitative PCR revealed that targeted mRNA was similarly regulated to miRNA. These results suggest that miRNAs of reproductive organs in dogs may be biological markers for aging and reproductive diseases and could be used for mediating aging.

Background: Cystic endometrial hyperplasia-pyometra complex (CEH-P) is one of the most common uteropathies in bitches. In diseases with mild or obscure clinical signs and normal uterine size, a diagnosis based on a clinical assessment might be incorrect. The main aim of the research was to determine the morphological variables accompanying uterine diseases in bitches in microscopic evaluation. Consequently, the obtained results can be used to create a new classification system for uterine pathological changes during the development of the CEH-P, diagnosed by microscopic examination in bitches. Material for the study consisted of the uteri of 120 female dogs, aged 1–16 years, obtained during routine ovariohysterectomies. Macroscopic observation after a longitudinal incision of the uterine horns, allowed a preliminary classification of the uteri into research groups: control group (physiological uteri), and groups GI-III uteri collected form bitches with varying degrees of endometrial pathology. These preliminary classifications were then verified by histological analysis (H&E stain). Results: The obtained results made it possible to determine and describe the prevalence (%) of pathological changes characteristic of the analyzed uterine diseases in the examined bitches. Histopathological analyses that were conducted have confirmed preliminary macroscopic evaluation for the control group, group GII (CEH), and group GIII (pyometra). In the uteri of the GI group, a severe congestion of the endometrium has been observed – this is typical of inflammation – which was not confirmed during histopathological examinations. However, these examinations revealed acute endometrial haemorrhage of varying severity. Conclusions: Early reproduction disorders in bitches are, in general, not confirmed by clinical signs in the examined animals. The results show that during classification of typical morphological changes in the endometrium over the development of the CEH-P complex in bitches microscopic examinations are required. The obtained results indicate a frequent lack of consistency in the macroscopic assessment and histological analysis of the endometrium, observed in the analyzed uterine diseases, which in most cases is not followed by clinical symptoms. The presented classification of uterine diseases may be useful as a diagnostic tool in reproductive disorders in bitches and in examination in the field of basic research. [ABSTRACT FROM AUTHOR]

Background: Pyometra or pyometritis is a serious and common condition of intact female dogs characterized by the inflammation of the uterus with a buildup of purulent exudate. It may be classified as open or closed. If untreated, pyometra can lead to uterine rupture and sepsis. Pyometra may also predispose to uterine torsion, defined as a rotation of one or both uterine horns around its longitudinal axis. Uterine torsion in female dogs is rare, and usually with late pregnancy or parturition. This case report describes the clinical presentation and therapeutic management of uterine torsion correlated with open pyometra in a non-gravid bitch with no history of exogenous progesterone exposure. Case: A 10-year-old intact Yorkshire Terrier bitch weighing 3.2 kg was referred to a veterinary clinic in Porto Alegre, Brazil, with a 7 day history of prostration, anorexia, polydipsia, and sanguinopurulent vulvar discharge. Physical examination revealed pronounced abdominal tenderness. On abdominal ultrasonography, the uterus was enlarged and filled with cellular anechoic content, suggestive of pyometra. A complete blood count showed mild microcytic normochromic anemia and leukocytosis. The animal was stabilized and an urgent ovariohysterectomy was performed. Preanesthetic analgesia consisted of subcutaneous methadone 0.3 mg/kg. Anesthesia was induced with propofol 3 mg/kg i.v. and maintained with inhaled isoflurane. During the procedure, significant enlargement of the left uterine horn and slight enlargement of the right uterine horn were observed. In addition, a torsion was identified near the left ovary, with copious sanguinopurulent secretion. The animal remained under observation and fluid therapy for 48 h after the procedure and was discharged to postoperative follow-up. After discharge, the following treatment was medicine, local cleaning and rest for 14 days. Concluding the therapeutic process with a satisfactory outcome. Discussion: Uterine torsion is considered rare in female dogs, and when it does occur, it is usually associated with late pregnancy or parturition. In this case, pregnancy was not a predisposing factor, but the animal had pyometra, which may have contributed to the torsion. Exogenous progesterone administration to inhibit the estrous cycle significantly increases the risk of pyometra; however, in the case reported herein, there was no history of progesterone therapy. The most likely cause was prolonged, repeated progesterone stimulation in the luteal phase, since the animal developed pyometra at the age of 10. Both uterine torsion and pyometra may progress to cause severe systemic complications. However, none was observed in the present case. Despite the high mortality rate, the animal survived, probably due to the open pyometra, which is associated with better prognosis than closed pyometra. Nevertheless, drainage was not enough to relieve enlargement of the uterus and ligaments, which may have facilitated torsion. Pyometritis associated with uterine torsion has rarely been reported in the literature, especially in small animals. Early diagnosis is key, as is surgical treatment via ovariohysterectomy. The surgical procedure had therapeutic purpose and was managed satisfactorily. The mechanism of uterine torsion has yet to be fully elucidated, which highlights the importance of this report. Additionally, it is rare in dogs, with very few reports in the non-gravid uterus. [ABSTRACT FROM AUTHOR]

In an 8-year period at two medical center, 138 patients underwent uterine artery embolization, and 11 of them were diagnosed with uterine necrosis. Among them, three were successfully conceived. However, one of them developed an arteriovenous malformation after an artificial abortion, and another experienced complications, including placenta previa and placenta accreta spectrum, which resulted in early preterm delivery and recurrent postpartum hemorrhage, necessitating subtotal hysterectomy. Therefore, it is crucial to prepare for potential adverse pregnancy outcomes in subsequent pregnancies for patients with a history of uterine necrosis.

Although gravid uterine incarceration is typically diagnosed during the early second trimester, we encountered two unusual cases in early pregnancy. A 34-year-old multiparous woman with adenomyosis presented at 7 + 2 weeks of gestation with increased urinary frequency and a sensation of incomplete bladder emptying. The uterine incarceration was successfully reduced by manual reduction and pessary insertion, and she delivered a normal infant at term. In the second case, a 31-year-old nulliparous woman with a large myoma complained of dysuria, acute urinary retention, and intense back pain at 6 weeks of gestation. Manual reduction was successful in the knee-chest position. Subsequent pessary insertion failed; however, a slight reduction in pain was achieved. After a week, the fetus spontaneously aborted. In summary, gravid uterine incarceration is a rare but potentially fatal condition for the fetus, and a suspicion of this condition in patients with urinary symptoms, especially urinary retention and pelvic pain, is important in the early gestation period.

Uterine disease early postpartum reduces fertility during the breeding period. One potential mechanism involves the reduced functional capacity of the uterus to support pregnancy. A second potential mechanism involves damage to ovarian follicles associated with systemic inflammation. We categorized lactating Holstein cows into healthy (n = 63) and diseased (n = 39) uterus groups based on the percentage of polymorphonuclear neutrophils in the uterine lumen during the second and third month postpartum and evaluated the functionality of their ovaries and their capacity to establish and maintain pregnancy. Cows were enrolled in a timed artificial insemination protocol (Presynch Ovsynch) so that the first artificial insemination was approximately 75 d postpartum. Ovarian follicles and corpora lutea were counted and measured using transrectal ultrasound, ovulatory responses were assessed, and luteal phase progesterone concentrations were measured. Pregnancy was detected on d 18, 20, 22, 25, 32, and 45 through chemical (d 18 to 25) or ultrasonographic methods (d 32 and 45). The percentage of cows ovulating during the Presynch period; the number, diameter, and ovulatory capacity of follicles during the Ovsynch period; and plasma progesterone concentrations following ovulation were similar for healthy and diseased cows. The initial period of pregnancy establishment (d 18 to 22) appeared to be unaffected by disease because a similar percentage of healthy and diseased cows were pregnant during this period. Embryonic loss occurred in both healthy and diseased cows after d 22. Based on a relatively small number of pregnancies (n = 30 healthy and n = 17 diseased), the cumulative embryonic loss after d 22 was greater in diseased compared with healthy cows. In short, uterine disease as defined in this study did not affect cyclicity, ovarian follicular growth, or plasma progesterone concentrations. Percentages of healthy and diseased cows that were pregnant were similar from d 18 to 22 after artificial insemination. Greater embryonic loss was observed after d 22 in diseased compared with healthy cows, but this observation was based on a small number of pregnancies and should be studied further in larger trials with greater statistical power. [ABSTRACT FROM AUTHOR]

The aim of the present study was to evaluate the biochemical profile and reproductive performance in postpartum dairy cows with clinical metritis. The research was carried out using performed on 213 pluriparous lactating cows from two dairy herds in southeast Brazil. Dairy cows were assigned into a group of healthy cows (n = 147) and cows with metritis (n = 66). Blood samples to assess serum albumin, cholesterol, fibrinogen, calcium, gamma‐glutammyltransferase (GGT), aspartate aminotransferase (AST) and β‐hydroxybutyrate (BHBA) concentrations were performed on day 8 ± 2 postpartum. Metritic cows had lower (p <.05) serum albumin, cholesterol and calcium concentration, and higher (p <.05) GGT and AST activity, and BHBA and fibrinogen concentrations when compared to the healthy group. The calving‐to‐conception interval and services per pregnancy were higher in metritic cows (p <.01) than in healthy cows and the conception rate at first service was lower in metric group (p <.01). Variable importance in projection plots demonstrated that cholesterol was the main discriminator between metritic and healthy cows. Our results indicated alterations in the biochemical profile and impaired reproduction performance in metritic cows. [ABSTRACT FROM AUTHOR]

This study compares serum markers for systemic inflammation, and liver, mineral, and energy status in samples obtained −7, 1, 3, 5, 7, 14 ± 1, 21 ± 1, and 35 d relative to calving from healthy dairy cows and those diagnosed with purulent vaginal discharge (PVD) or subclinical endometritis (SCE). Metabolites and markers measured in serum were total calcium, total protein, albumin, globulin, cholesterol, urea, glucose, gamma-glutamyl transferase, aspartate aminotransferase, glutamate dehydrogenase, β-hydroxybutyrate (BHB), non-esterified fatty acids (NEFA), haptoglobin (Hp), and insulin-like growth factor-1 (IGF-1). Holstein cows with no recorded clinical disease were classified healthy (neither PVD nor SCE; n = 38), PVD (n = 10) or SCE (n = 10) at 35 d postpartum. The cut-point for PVD was mucopurulent vaginal discharge or worse, measured with Metricheck, and for SCE > 5% endometrial polymorphonuclear cells (PMN). Purulent vaginal discharge and SCE were mutually exclusive categories. The association of each serum marker with reproductive tract health classification was fitted in mixed linear regression models, accounting for repeated measures, sampling day, parity, BCS, and interactions of reproductive tract status and day. Serum Hp concentrations were greater at 3, 5, 7, and 14 ± 1 d postpartum for SCE and at 7 and 35 d postpartum for PVD than in healthy cows. Albumin concentrations were lesser for PVD than healthy at 14 ± 1 d postpartum and lesser for SCE than healthy at 35 d postpartum. The week before calving, SCE had lesser total calcium than healthy cows, and at 7 and 14 ± 1 d postpartum PVD had lesser total calcium than healthy cows. At 14 ± 1 d postpartum, serum NEFA, BHB, and globulin were greater, and IGF-1 lower for SCE than PVD or healthy cows. For all other metabolites, no differences were found. Before diagnosis, PVD or SCE had more indication of postpartum systemic inflammation (high Hp and low albumin) than healthy cows, and markers of energy status were more compromised in SCE than in PVD or healthy cows. This supports the hypothesis that SCE is associated with maladaptation to postpartum metabolic demands and with metabolic inflammation. • Cows diagnosed with PVD or SCE at 35 d postpartum have greater Hp concentrations than healthy cows. • NEFA, BHB, IGF-1 and cholesterol differed in cows that were later diagnosed with SCE. • Variations in the energy metabolism and inflammatory profile precede distinct manifestations of reproductive tract disease. [ABSTRACT FROM AUTHOR]

Endometritis, diagnosed either by assessing the proportion of nucleated cells that are neutrophils (PMN%) following cytology of the endometrium or by assessing the degree of purulent material within the vagina (purulent vaginal discharge or PVD score), is prevalent among dairy cows. However, limited data exist as to the degree of variation among herds in the prevalence of endometritis diagnosed by these 2 methods. Thus, we undertook a study involving uterine cytological and vaginal sampling at a median of 41 d in milk of 1,807 cows from 100 seasonally breeding dairy herds in New Zealand. The optimal cut-point for PMN% was determined by receiver operator characteristic (ROC) curve analysis using conception to first artificial insemination (AI) as the outcome variable. The prevalence of disease was then calculated at the cow and herd levels, and an estimate of the effect of clustering of cow within a herd was calculated. Reproductive outcomes were collated and associations between endometritis and reproductive outcomes assessed using multivariable models. The optimal PMN% cut-point was ≥2%. The correlation of results for cows within a herd (the intraclass correlation) was 0.03, which was significant; hence, subsequent modeling accounted for this clustering. The cow-level prevalence of PMN% ≥2% was 27.0% [95% confidence interval (CI): 25.0 to 29.1%], whereas the mean within-herd prevalence of PMN% ≥2% was 27.1% (95% CI: 24.7 to 29.6%; range: 5.0 to 63.6%), and the prevalence among herds varied significantly. An elevated PMN% (≥2%) was significantly associated with a reduction in the proportion of cows conceiving to first AI (45.8 vs. 54.5%), a reduced proportion of cows submitted for AI in the first 3 wk of the seasonal breeding program (83.7 vs. 89.3%), and a lower proportion pregnant in the first 3 (44.4 vs. 55.4%) and 6 wk (67.5 vs. 76.4%) of the breeding program relative to cows with a low PMN% (i.e., <2%). A total of 24.6% of cows had a PVD score ≥2. The herd mean prevalence of PVD score ≥2 was 25.1% (95% CI: 22.5 to 27.7%; range: 5.0 to 65.0%) and varied significantly among herds. The level of agreement (kappa) between the PVD score and PMN% was low (16.8%) and nonsignificant. The effects of PVD score and PMN% on reproductive outcomes were independent. The within-herd median prevalence of endometritis based on combining both diagnostic tests and using a Bayesian latent class model was 22.9% (Bayesian 95% CI: 10.4 to 40.1%). We conclude that more than one-fifth of dairy cows have endometritis diagnosed either by PMN% or PVD in seasonal breeding herds when assessed at an average of 41 DIM, which was, on average, 30 d before the start of the seasonal breeding program. There is large and unexplained variation in prevalence of endometritis among herds. The 2 diagnostic methods were both associated with reproductive outcomes but have low levels of agreement between them and their effects appear to be independent. [ABSTRACT FROM AUTHOR]

Endometritis is an inflammation of the endometrium associated with bacterial infection. The pathogenesis of endometritis in cows is still not completely understood. The combined analysis of the markers of inflammation and oxidative stress has contributed to a better understanding of disease mechanisms, but is still unexplored in uterine disorders. Moreover, research provides evidence about an important role of the vagus nerve in regulating the innate immune function through the cholinergic anti-inflammatory pathway in response to bacterial infections. This new pathway has demonstrated a critical role in controlling the inflammatory system. The aim of this study was to evaluate the activity of cholinesterase in total blood, lymphocytes, and serum of dairy cows with clinical and subclinical endometritis. Sixty-one Holstein cows, between 30 and 45 days in milk, were classified into 3 groups of animals: presenting clinical endometritis (n = 22), subclinical endometritis (n = 17), and healthy (n = 22). Mean leukocyte counts did not differ among groups, but the neutrophil number was significantly higher in cows with clinical endometritis than those in healthy animals. Also, serum concentration of interleukin-1beta (pg/mL) was significantly higher in cows with endometritis. The activity of acetylcholinesterase in blood and lymphocytes increased in both groups with endometritis. Animals with endometritis presented an increase in lipid peroxidation, but the antioxidant enzyme activity (catalase levels) was higher in endometritis groups than in normal cows. In conclusion, the inflammatory process of clinical and subclinical endometritis leads to systemic lipid peroxidation despite the compensatory increase of the antioxidant enzyme. These data also provide evidence of an important role of the cholinergic pathway in regulating dairy cows with clinical and subclinical endometritis. [ABSTRACT FROM AUTHOR]

Diffusion tensor imaging (DTI) is able to quantify the velocity and direction of water molecules in human tissues, thus to reflect micro-structure of tissues as well as physiological and pathological changes. DTI related parameters fractional anisotropy (FA) and apparent diffusion coefficient (ADC) value can reveal microscopic structure quantitatively. Fiber tractography (FT) can visually display the direction and distribution of fiber bundles, providing more anatomical details noninvasively. Presently, the application of DTI in uterus has come to increasingly attention. DTI can well display fibrous structure of normal uterus and also be applied in uterine diseases, for instance, the differentiation of ordinary to degenerative uterine leiomyoma and postoperative efficacy evaluation after ultrasound ablation, the preoperative staging of endometrial and cervical cancer, determination of lymph node metastasis and prognosis evaluation, showing the microstructure of sacral nerve root to reflect the pathophysiological changes of endometriosis, providing more information for clinical diagnosis and contributes to the follow-up treatment options and prognosis evaluation. [ABSTRACT FROM AUTHOR]

This new 4-page document discusses the reproductive consequences of uterine disease in the dairy cow, potential mechanisms, and current treatments. Written by Rachel L. Piersanti and John J. Bromfield, and published by the UF/IFAS Department of Animal Sciences, March 2019. http://edis.ifas.ufl.edu/an354

Purulent vaginal discharge (PVD) is a prevalent uterine disease of dairy cows during the puerperium that affects the milk production and affects the profitability of farms. The objectives of this study were to evaluate the biochemical profile, the body condition score, the milk production of cows with PVD and the effects PVD on reproductive performance. A total of 338 Holstein dairy cows aged from 3 to 5 years, from three commercial dairy farms, from Brazil, were used. Blood samples were collected within 25 ± 3 days post‐partum from Holstein dairy cows without PVD (control cows, n = 242) and cows with PVD (n = 96), based on scoring of the vaginal discharge. The body condition score and milk production were recorded on the day of sampling. The biochemical profile encompassed albumin, urea, gamma‐glutamyl transferase, calcium, fibrinogen and cholesterol concentrations. The number of services per pregnancy was lower (p < 0.01), and the number of days until first insemination and the median time to pregnancy were higher in cows with PVD (p < 0.01) when compared with control cows. Milk production and body condition score were lower (p < 0.01) in cows with PVD than in control group. Cows with PVD had lower (p < 0.05) serum albumin, urea, calcium and cholesterol concentrations, and higher serum gamma‐glutamyl transferase activity and fibrinogen concentration than cows without PVD. Our results show that cows with PVD have changes in the biochemical profile and negative effects on production and reproduction performance. [ABSTRACT FROM AUTHOR]

Background: Uterine twisting in bitches is an uncommon disease in which the difficulty of diagnosis is due to nonspecific clinical signs. This condition is more commonly observed in pluriparous females and is usually associated with a pregnant uterus close to birth, or associated with hemometra, pyometra and neoplasms in non-pregnant bitches. This study reports a case of an 11-year-old Poodle bitch with a rare case of uterine twisting in a non-pregnant womb. Case: A 11-year-old Poodle dog, weighing 3.2 kg, was admitted at the institution with a history of anorexia, oligodipsia and apathy during one day. There was no information on the last phase of estrus or previous pregnancies. The patient arrived at the emergency room of the veterinary hospital with cardiorespiratory arrest and was resuscitated with mechanical ventilation, cardiac massage and administration of adrenaline (0.1 mg/kg IV, 1 mg/ml concentration), tramadol hydrochloride (2 mg/kg via IV) and oxygen therapy. Clinical examination revealed a distended and tense abdomen with a palpable mass in the mesogastric region. Ultrasound examination showed a heterogeneous structure (> 10cm. in diameter), with cavitary areas filled with heterogeneous anechoic content and septations, located between the liver and urinary bladder. It was not possible to identify in which organ or structure the mass originated, and the possibility of gestation and fetal death was discarded. The female died six hours after admission. The patient was submitted to necropsy and histopathological analysis revealed a dark red and enlarged segment of the uterine horn with a 360° twist, occupying most of the abdominal cavity. The left uterine horn was about 10 cm in diameter and firm, and cystic areas were observed on a reddish-black surface containing a large amount of bloody fluid. The right uterine horn was normal in appearance, but with a small amount of fluid, slightly viscous and translucent. The histopathological examination of the structure found in the left uterine horn showed areas of partially organized hematomas with red blood cells inside the vessels, without neoplastic or inflammatory cells. The definitive diagnosis was unilateral uterine twist, unrelated to the gestational or neoplastic process. Discussion: Uterine twist is an uncommon problem in most domestic species. The occurrence of this condition is higher in the gravid uterus, usually in pluriparous females at the end of gestation or delivery, or in non-pregnant bitches secondary to hemometra or pyometra. During uterine twist, occlusion of blood vessels occurs, with subsequent engorgement and vascular rupture, leading to intraluminal hemorrhage and tissue ischemia, which may lead to extravasation of blood into uterine lumen. Thus, the main suspect for the occurrence of unicornual twisting was hemometra in the left uterine horn, associated with relaxation of the uterine ligaments due to the advanced age of the patient. These factors may have favored abnormal mobility and the twist of the organ within the abdominal cavity, even in the absence of the most common predisposing factors, such as gestation and delivery. The rarity of the case is highlighted by the absence of a gestational process associated with the condition. In addition, due to the non-specific clinical signs, the difficulty in the accurate and immediate diagnosis was demonstrated, as well as the potential to cause a rapid clinical deterioration of the patient. [ABSTRACT FROM AUTHOR]

Spontaneous endometriosis is common in women, great apes and Old World monkeys, but rare in New World monkeys. We report on the clinical diagnosis and successful combination of surgical and medical treatment in a case of spontaneous endometriosis in a diabetic hooded capuchin. Addressing this painful condition had a positive welfare impact. [ABSTRACT FROM AUTHOR]

Bacterial contamination of the uterus following calving is ubiquitous in the dairy cow, 40% of cows develop postpartum uterine infection, including metritis. While predisposing factors like twinning and dystocia are associated with metritis, it is unclear why some cows remain healthy following calving and others develop uterine infection, negatively impacting animal health, milk production and economic return. Here, we profiled peripheral blood mononuclear cells of cows before calving and during postpartum metritis. We hypothesized that peripheral blood mononuclear cell function and proportions would be altered during the prepartum period in cows that develop postpartum metritis. Using flow cytometry we observed reduced proportions of peripheral CD3 + /CD4 + , CD4 + /CD62L + , FOXP3 + and CD21 + populations from −10 to 40 days relative to calving associated with metritis, while the proportion of peripheral CD3 + /CD4 + lymphocytes were specifically reduced in the prepartum period before the onset of metritis. Peripheral blood mononuclear cells from cows with metritis had a perturbed capacity to secrete IL-1β or IFNγ in response to in vitro stimulus; cells collected during the prepartum period from cows that would go on to develop metritis failed to increase IL-1β secretion in response to stimulation, while IFNγ secretion was altered at calving and postpartum in cows with metritis compared to healthy herd mates. No effect of metritis was observed in the capacity of cows to mount a humoral immune response to antigen administered on the day of calving. The studies discussed here suggest that while minor changes to the prepartum immune system are observed in cows that develop metritis, changes observed in the postpartum period are more prevalent and likely a consequences of disease and not causative. Future studies to modulate the prepartum immune system may help to limit postpartum metritis. [ABSTRACT FROM AUTHOR]