The roles of Braun Lipoprotein in inducing tolerance of bovine endometrium infected by Escherichia coli.

Escherichia coli (E. coli), a Gram-negative bacterium, is the primary pathogen responsible for endometritis in dairy cattle. The outer membrane components of E. coli, namely lipopolysaccharide (LPS) and bacterial lipoprotein, have the capacity to trigger the host's innate immune response through pattern recognition receptors (PRRs). Tolerance to bacterial cell wall components, including LPS, may play a crucial role as an essential regulatory mechanism during bacterial infection. However, the precise role of Braun lipoprotein (BLP) tolerance in E. coli-induced endometritis in dairy cattle remains unclear. In this study, we aimed to investigate the impact of BLP on the regulation of E. coli infection-induced endometritis in dairy cattle. The presence of BLP was found to diminish the expression and release of proinflammatory cytokines (IL-8 and IL-6), while concurrently promoting the expression and release of the anti-inflammatory cytokine IL-10 in endometrial epithelial cells (EECs). Furthermore, BLP demonstrated the ability to impede the activation of MAPK (ERK and p38) and NF-κB (p65) signaling pathways, while simultaneously enhancing signaling through the STAT3 pathway in EECs. Notably, BLP exhibited a dual role, acting both as an activator of TLR2 and as a regulator of TLR2 activation in LPS- and E. coli-treated EECs. In E. coli-infected endometrial explants, the presence of BLP was noted to decrease the release of proinflammatory cytokines and the expression of HMGB1, while simultaneously enhancing the release of anti-inflammatory cytokines. Collectively, our findings provide evidence that the bacterial component BLP plays a protective role in E. coli-induced endometritis in dairy cattle.

Inflammation in recurrent miscarriage - a comprehensive perspective from uterine microenvironment and immune cell imbalance to therapeutic strategies.

Recurrent miscarriage, poses a significant challenge for many couples globally, the causes of which are not fully understood. Recent studies have shown the intricate link between uterine inflammation and recurrent miscarriages. While inflammation is essential during early pregnancy stages, especially in embryo implantation, an imbalance can lead to miscarriage. Key inflammatory mediators and an imbalance in immune cells can significantly alter and contribute to recurrent miscarriages. Lifestyle factors like smoking and obesity exacerbate inflammatory responses, increasing miscarriage risks. Understanding the interaction between the uterine environment, immune cell imbalances, and recurrent miscarriages is essential for devising effective treatments. This paper presents the latest data on inflammation's role in recurrent miscarriage, emphasizing the significance of diagnosing chronic endometritis and immune imbalances, offering practical recommendations for treatment and diagnosis.

Interaction Between Chronic Endometritis Caused Endometrial Microbiota Disorder and Endometrial Immune Environment Change in Recurrent Implantation Failure.

Objective: To investigate the Interaction between chronic endometritis (CE) caused endometrial microbiota disorder and endometrial immune environment change in recurrent implantation failure (RIF). Method: Transcriptome sequencing analysis of the endometrial of 112 patients was preform by using High-Throughput Sequencing. The endometrial microbiota of 43 patients was analyzed by using 16s rRNA sequencing technology. Result: In host endometrium, CD4 T cell and macrophage exhibited significant differences abundance between CE and non-CE patients. The enrichment analysis indicated differentially expressed genes mainly enriched in immune-related functional terms. Phyllobacterium and Sphingomonas were significantly high infiltration in CE patients, and active in pathways related to carbohydrate metabolism and/or fat metabolism. The increased synthesis of lipopolysaccharide, an important immunomodulator, was the result of microbial disorders in the endometrium. Conclusion: The composition of endometrial microorganisms in CE and non-CE patients were significantly different. Phyllobacterium and Sphingomonas mainly regulated immune cells by interfering with the process of carbohydrate metabolism and/or fat metabolism in the endometrium. CE endometrial microorganisms might regulate Th17 response and the ratio of Th1 to Th17 through lipopolysaccharide (LPS).

Live S. aureus and heat-killed S. aureus induce different inflammation-associated factors in bovine endometrial tissue in vitro.

Staphylococcus aureus is majorly involved in bovine mastitis; however, it weakly induces pro-inflammatory factors in mammary gland epithelial cells. We aimed to clarify the involvement of S. aureus in other inflammation types and its relationship with inflammatory factor secretion in bovine endometritis. We used live S. aureus (LSA)- and heat-killed S. aureus (HK-SA)-treated bovine endometrial tissue in vitro. The HK-SA-treated group showed significantly higher IL-6, IL-1ß, TNF-α, CXCL1/2 and TLR2 expression than the LSA-infected group. Contrastingly, the LSA-infected group showed significantly higher PTGS2, mPGES-1, and EP4 expression than the HK-SA treated group. There was no significant between-group difference in hyaluronan-binding protein 1 expression, which suggested similar inflammatory responses. H&E results indicated that LSA and HK-SA induced shedding of endometrial gland epithelial cells. The LSA-infected group showed higher high-mobility group box 1 protein expression than the HK-SA treated groups, which indicated differences in signaling pathway activation. Further, the LSA-treated group had higher JNK and p38 MAPK levels while the HK-SA-treated group had higher IκB-α levels. There was no significant between-group difference in the ERK signaling pathway. Our findings indicate that the pathogen-associated molecular patterns (PAMPs) of S. aureus activate pro-inflammatory factor expression via the TLR2-ERK-NF-κB signaling pathway. Contrastingly, LSA induced PGE2 accumulation via the TLR2/MAPKs signaling pathway. This is the first report that S. aureus and the PAMPs of S. aureus activate different signaling pathways and that LSA mainly induce PGE2 accumulation rather than cytokine secretion.

MiR-193a-3p targets LGR4 to promote the inflammatory response in endometritis.

Solving the reproductive barriers of dairy cows has become one of the most critical factors determining the dairy industry's development. Clinically, inflammation disease like endometritis is the most crucial cause in reducing dairy production's financial viability. MiR-193 family can induce cell apoptosis and differentiation has been reported in various diseases. LGR4 plays a vital role in reproductive system development and immune system regulation, and it is closely related to animal reproductive function and cytokine regulation. In this study, we observed a negative relationship between miR-193a-3p and LGR4 expression level in both inflammatory tissues and cells. The expression level of miR-193a-3p and LGR4 in bovine endometrial epithelial cells (BENDs) is regulated by lipopolysaccharide (LPS) stimulation time and dose-dependent. Subsequently, miR-193a-3p mimics and inhibitors were used to explore its functions in the inflammation response process, finding that overexpression of miR-193a-3p markedly increases the expression level of pro-inflammatory cytokines induced by LPS, such as IL-1ß, IL-6 and TNF-α, while the group in which transfected inhibitor is on the contrary. Of note, immunofluorescence and western blot results showed that miR-193a-3p enhanced LPS-induced NF-κB p65 phosphorylation through targeting LGR4, whereas inhibiting miR-193a-3p could suppress the activation of NF-κB pathway significantly. In conclusion, our study firstly reported the mechanism by which miR-193a-3p targets LGR4 to elevate the inflammatory response in bovine endometrium injury, thereby implying that knockdown miR-193a-3p may lay the theoretical and practical basis for drug development of alleviating endometritis in dairy cows.

Enforced expression of miR-92b blunts E. coli lipopolysaccharide-mediated inflammatory injury by activating the PI3K/AKT/ß-catenin pathway via targeting PTEN.

Endometritis is a reproductive disorder characterized by an inflammatory response in the endometrium, which causes significant economic losses to the dairy farming industry. MicroRNAs (miRNAs) are implicated in the inflammatory response and immune regulation following infection by pathogenic bacteria. Recent miRNA microarray analysis showed an altered expression of miR-92b in cows with endometritis. In the present study, we set out to investigate the regulatory mechanism of miR-92b in endometritis. Here, qPCR results first validated that miR-92b was down-regulated during endometritis. And then, bovine endometrial epithelial cells (BEND cells) stimulated by high concentration of lipopolysaccharide (LPS) were employed as an in vitro inflammatory injury model. Our data showed that overexpression of miR-92b significantly suppressed the activation of Toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) in LPS-stimulated BEND cells, thereby reducing pro-inflammatory cytokines release and inhibiting cell apoptosis. Looking into the molecular mechanisms of regulation of inflammatory injury by miR-92b, we observed that overexpression of miR-92b restrained TLR4/NF-κB by activating the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT)/ß-catenin pathway. Furthermore, the luciferase reporter assay suggested that miR-92b targeted inhibition of phosphatase and tensin homolog (PTEN), an inhibitor of the PI3K/AKT/ß-catenin pathway. Importantly, in vivo experiments confirmed that up-regulation of miR-92b attenuated the pathological injury in an experimental murine model of LPS-induced endometritis. Collectively, these findings show that enforced expression of miR-92b alleviates LPS-induced inflammatory injury by activating the PI3K/AKT/ß-catenin pathway via targeting PTEN, suggesting a potential application for miR-92b-based therapy to treat endometritis or other inflammatory diseases.

MicroRNA: Could It Play a Role in Bovine Endometritis?

Endometritis in dairy cows is a major economic problem worldwide; without advances in lifestyle management and drug treatment, it causes high morbidity and death. Micro ribonucleic acid (miRNAs) these days is seen as an important part of gene control networks. It is a class of small nucleotides 20-25, single-stranded RNA molecules. In endometritis, the inflammatory response caused by the gram-negative bacteria Escherichia coli (E. coli) alters the expression of miRNA which can regulate the innate immune system. This manuscript reviews (1) the interaction of miRNAs with the signaling of NF-κB and dysregulation of miRNAs and NF-κB activity in endometritis and (2) the activity of miR-let-7c, miR-148a, and miR-488 in NF-κB activation and their effect on endometritis. Cows with reduced immunity are more vulnerable to transition diseases, such as endometritis. During post-partum, cows undergo stress, metabolic disorders, hormonal imbalance, negative energy balance, and changes in diet. One of the many categories of regulatory molecules, which explain its natural function and pathological impact on NF-κB dysregulation, is important to inform the complexity of the immune system and to develop treatments for endometritis. It shows that miRNAs could have multiple applications in veterinary medicine. Nevertheless, a comprehensive study of is essential which should be aimed at exploring the role of microRNA at physiological level and its effect due to dysfunction and dysregulation.

Beta-endorphin inhibits the inflammatory response of bovine endometrial cells through δ opioid receptor in vitro.

Postpartum uterine infections are common reproductive diseases in postpartum cows. Evidence has shown that plasma ß-endorphins increase during bovine uterine inflammation. However, the effect of ß-endorphins on the inflammatory response in bovine endometrium has not been clarified. The aim of this study was to investigate the effect of ß-endorphins on the inflammatory response of bovine endometrial epithelial and stromal cells, and to explore the possible mechanism. The cells were treated with E. coli lipopolysaccharide (LPS) to simulate inflammation, which was characterized by the significant activation of NF-κB signaling pathway and the increased gene expression of the downstream proinflammatory cytokines (approximately 1.2- to 15-fold increase, P < 0.05). By using Western blot and qPCR techniques, we found that ß-endorphins inhibited the key protein expression of NF-κB pathway, and the gene expressions of TNF, IL1B, IL6, CXCL8, nitric oxide synthase 2, and prostaglandin-endoperoxide synthase 2 (P < 0.05). The co-treatment of ß-endorphins and opioid antagonists showed that the anti-inflammatory effect of ß-endorphins could be blocked (P < 0.05) by non-selective opioid antagonist naloxone or δ opioid receptor antagonist ICI 154129, but not the µ opioid receptor antagonist CTAP (P > 0.05). In conclusion, ß-endorphins may inhibit the inflammatory response of bovine endometrial epithelial and stromal cells through δ opioid receptor.

Eutopic endometrium from women with endometriosis and chlamydial endometritis share immunological cell types and DNA repair imbalance: A transcriptome meta-analytical perspective.

The aim of this study was to identify the key similarities between the eutopic endometrium of women with endometriosis and chlamydia-induced endometritis taking into account tissue microenvironment heterogeneity, transcript gene profile, and enriched pathways. A meta-analysis of whole transcriptome microarrays was performed using publicly available data, including samples containing both glandular and stromal endometrial components. Control samples were obtained from women without any reported pathological condition. Only samples obtained during the proliferative menstrual phase were included. Cellular tissue heterogeneity was predicted using a method that integrates gene set enrichment and deconvolution approaches. The batch effect was estimated by principal variant component analysis and removed using an empirical Bayes method. Differentially expressed genes were identified using an adjusted p-value < 0.05 and fold change = 1.5. The protein-protein interaction network was built using the STRING database and interaction score over 400. The Molecular Signatures Database was used to analyse the functional enrichment analysis. Both conditions showed similarities in cell types in the microenvironment, particularly CD4+ and CD8+ Tem cells, NKT cells, Th2 cells, basophils, and eosinophils. With regards to the regulation of cellular senescence and DNA integrity/damage checkpoint, which are commonly enriched pathways, 21 genes were down-regulated and directly related to DNA repair. Compared to the endometriosis samples, some chlamydial endometritis samples presented a lack of enriched immune pathways. Our results suggest that both conditions show similar distributions of microenvironment cell types, the downregulation of genes involved in DNA repair and cell cycle control, and pathways involved in immune response evasion.

Hydroxysafflor Yellow A Inhibits Staphylococcus aureus-Induced Mouse Endometrial Inflammation via TLR2-Mediated NF-kB and MAPK Pathway.

The present study is designed to investigate the effect of hydroxysafflor yellow A (HYA) on Staphylococcus aureus (S. aureus)-induced mouse endometrial inflammation and to explore its molecular mechanism. We established a mouse endometritis model by intrauterine injection of S. aureus and intrauterine injection of HYA for treatment. Immunohistochemistry, immunofluorescence, and Western blot were used to detect protein expression in uterine tissue, and qPCR was used to measure mRNA expression. HYA could significantly weak uterine pathological changes caused by S. aureus and reduce MPO activity, CD45, CD3, and ED-1 protein expression in uterine tissues of S. aureus-infected mice. Similarly, HYA also significantly decreased S. aureus induced the increase in TNF-α, IL-1ß, and IL-6 in uterine tissue. In vivo, we found that knockdown of TLR2 was very important could significantly reduce S. aureus induced the elevated expression of TNF-α, IL-1ß, and IL-6 in mEECs. Importantly, in terine tissues of S. aureus-infected mice, HYA significantly decreased the ratio of p-p65/p65, p-IKBα/IKBα, p-p38/p38, p-Erk/Erk, and p-JNK/JNK expression. HYA displays anti-inflammatory effects on S. aureus mouse endometrial inflammation, and this effect might be related to HYA which could block TLR2-mediated NF-kB and MAPK pathway.

Diagnosis of chronic endometritis: How many CD138+ cells/HPF in endometrial stroma affect pregnancy outcome of infertile women?

PROBLEM: The definition of chronic endometritis (CE) differs among studies, and currently, there is no accepted consensus. This study aimed to establish the minimum number of immunohistochemical analysis of CD138+ plasma cells to identify a clinically relevant CE. METHOD OF STUDY: We performed a retrospective study on 716 infertile patients who never did CE analysis and respective antibiotic treatment before. Samples were obtained by endometrial scratching in the mid-luteal phase before IVF-ET treatment. The number and distribution of CD138+ cells were analyzed by immunohistochemistry. Thirty high-power fields (HPF) were evaluated for each sample. Patients were classified in 2 main groups: (a) CD138low (<5 CD138+ cells in all HPFs), (b) CD138high (≥5 CD138+ cells in at least one HPF). Pregnancy outcome was compared among the groups. RESULTS: In the CD138high group, ß-hCG positive rate, clinical pregnancy rate and live birth rate were significantly decreased (P = .04, P = .01, P = .04, respectively). Also after adjusting for patient age, body mass index (BMI), and clinical characteristics, the ß-hCG positive rate (P = .05), clinical pregnancy rate (P = .01) and live birth rate (P = .02) were significantly lower in the CD138high than those in the CD138low group. Within the CD138low group, these parameters were not significantly different between patients without any plasma cells and patients with up to 4 plasma cells/HPF. CONCLUSION: We conclude that immunohistochemical analysis of CD138+ cells is a reliable method to detect CE which can be identified by the presence of ≥5 plasma cells in at least one out of 30 HPF.

Peripartum changes in the activity and expression of neutrophils may predispose to the postpartum occurrence of metritis in dairy cows.

Metritis is a postpartum uterine pathology that causes a huge economic loss due to increased culling risk and impaired milk yield and reproduction in cows. The present study was carried out to study the changes in the activity and expression of blood neutrophils in crossbred dairy cows with and without metritis. Collection of blood samples was done at -3, -2 and - 1 weeks before calving, at calving and during the first day of metritis diagnosis in metritis group (n = 8) or at day 8-10 post calving in healthy group (n = 8). Neutrophils were studied for its percentage (microscopically), respiratory burst (nitro blue tetrazolium assay), myeloperoxidase (MPO) concentrations (sandwich ELISA) and expression of CXCR1, CXCR2, TLR2, TLR4, GRα, CD11b, CD14, CD25, CD44, CD47 and CD62L (RT-PCR). Immunocytochemistry was used to investigate MPO concentration and CD14 activity, and western blotting was used for estimating MPO. Although most of these parameters changed in the cows that developed metritis one week before calving, MPO and CD14 got altered much earlier. Myeloperoxidase concentrations and expression of CD14 were considerably lower starting from -2 weeks before calving in cows that developed metritis compared to healthy cows. Further studies are warranted to study the possible use of MPO and CD14 to identify transition cows more vulnerable to develop metritis several weeks before disease occurrence.

Alteration in endometrial helper T-cell subgroups in chronic endometritis.

PROBLEM: The effect of chronic endometritis (CE) on the subpopulation of CD4+ T cells, Th1, Th2, Th17, and regulatory T cells in the endometrium is unknown. METHOD OF STUDY: Lymphocytes were isolated from the endometrium of CE patients (n = 12) and non-CE patients (n = 7). The CD4+ T-cell profile was analyzed by flow cytometry and immunofluorescence. RESULTS: In the endometrium of CE patients, there were significantly more Th1 cells among CD4+ cells and fewer Th2 cells in comparison to non-CE patients. No marked difference was observed in Th17 cells or Foxp3+ Treg cells. Moreover, the proportion of Th1 cells increased and the proportion of Th2 cells decreased as the number of CD138+ cells increased. Furthermore, when the localization of CD138+ cells and CD4+ cells was examined, CD4+ cells were found to be clustered around CD138+ cells in CE patients. CONCLUSION: The CD4+ T-cell profile in the endometrium is altered in women with CE. This finding may help to clarify the pathophysiology and development of treatment methods for CE.

Curcumin inhibits lipopolysaccharide and lipoteichoic acid-induced expression of proinflammatory cytokines and production of PGE2 in the primary bubaline endometrial stromal cells.

Infection of the uterus with Gram-positive Trueperella pyogenes and Gram-negative Escherichia coli is a common cause of postpartum endometritis in the cattle and buffalo and the condition is treated with antimicrobial drugs. The presence of drug residues in the milk and development of resistant bacteria necessitate the evaluation of alternate therapies for endometritis. Accordingly, we tested the immunomodulatory effect of curcumin in the bubaline endometrial stromal cells after treatment with the lipoteichoic acid (LTA) of Gram-positive Staphylococcus aureus and lipopolysaccharide (LPS) of Gram-negative E. coli that activate toll-like receptors (TLR-2 and TLR-4, respectively). Confluent primary culture of endometrial stromal cells was treated with LTA (1 µg/mL) and/or LPS (0.1 µg/mL), in the presence or absence of curcumin (30 µM for 24 h). PGE2 was assayed in the supernatant and the relative expression of proinflammatory cytokines (PICs) (IL1B, IL6, IL8 and TNFA) transcripts were quantified using real-time PCR. LTA was not effective in stimulating PGE2 production or upregulating the PIC expression except IL8. LTA+LPS increased PGE2 production and upregulated IL6 and IL8 genes. Curcumin inhibited the basal and LTA+LPS induced production of PGE2 and upregulation of PIC production. It was apparent that LPS, but not LTA, is a potent stimulator of PGE2 from the bubaline endometrial stromal cells. Curcumin downregulated the expression of LPS and/or LTA induced PICs and PGE2 and may be an alternate to antimicrobial drugs for the therapeutic management of endometritis.

Circadian Variations in Cellular Composition of Lymphoid Organs in Rats with Experimental Endomyometritis.

Circadian variations in the cellular composition of the lymphoid organs were studied in female Wistar rats under normal conditions and in experimental endomyometritis. The fractions of CD8+ cells (effector killers), CD25+ cells (activated/immature lymphocytes), as well as large, medium, small lymphocytes and monocytes/macrophages were assessed at 10.00 and 20.00 h. In the thymus and spleen of rats with endomyometritis, the number of parameters demonstrating significant circadian variations was lower than in intact animals. In the lymph nodes, morning/evening differences appeared for the number of CD8+ and CD25+ cells and monocytes/macrophages in the para-aortic lymph nodes, the number of large and small lymphocytes and CD8+ cells in inguinal lymph nodes, and in the number of large lymphocytes, CD8+ cells, and monocytes/macrophages in the ileal lymph nodes. Thus, the development of chronic inflammation in the uterine and vaginal mucosa was accompanied by desynchronosis in the immune system. Hence, circadian rhythms should be taken into consideration in the diagnosis and treatment of the disease.

Comparative Assessment of Leukocyte Infiltrate Composition in the Uterine and Vaginal Tissues in Rats with Experimental Endomyometritis Treated with Interferon-γ at Different Times of the Day.

The cell composition of leukocyte infiltrates in the endometrium, myometrium, and vaginal walls was studied in Wistar rats with modeled chronic endomyometritis after administration of IFNγ (0.1 µg/100 g body weight) in different daily regimens (10.00 or 20.00). Morning injections of this cytokine ameliorated inflammatory infiltration of the uterine wall and vagina, but increased the content of neutrophils in the endometrium. Evening cytokine injections reduced neutrophilic infiltration, enhanced mononuclear infiltration, and had no effect on plasmacytic infiltration of the uterine and vaginal walls. In the vaginal wall, both IFNγ administration schedules decreased neutrophil content. The data indicate the necessity to take into account the circadian rhythms in IFN therapy.

Inhibition of TLR2/TLR4 alleviates the Neisseria gonorrhoeae infection damage in human endometrial epithelial cells via Nrf2 and NF-Kßsignaling.

BACKGROUND: Neisseria gonorrhoeae (N.g) is Gram-negative bacteria and can lead to endometritis in female. Toll-like receptors regulate immune response in various diseases. However, the roles of TLR2 and TLR4 in. Neisseria gonorrhoeae-induced infection damage in human endometrial epithelia were investigated. METHODS: hEECs were infected with N.g (MOI 10 and 100) and cell viability and apoptosis were measured by CCK8 and flow cytometry assays in both infected groups with the uninfected normal hEECs as negative control. TLR2/TLR4 proteins were measured by ELISA method. Pro-inflammatory markers NLRP3, PGES (PGE2) and TNF-α were assessed by RT-qPCR (mRNA expression) and Elisa (protein concentrations). Transfection assays were performed to up- or down- regulate expression of TLR2 and TLR4 so as to study the functions of TLR2/TLR4 in. N.g-infected hEECs, followed by apoptosis and inflammation assessment. Similarly, we explored the interactions between TLR2/TLR4 and Nrf2/NF-κB/p65 by knocking down TLR2/TLR4 to detect the signaling and further regulating the signaling to evaluate TLR2/ TLR4, apoptosis and inflammation in cells. RESULTS: N.g suppressed cell viabilities and induced cell apoptosis and inflammation. TLR2/TLR4 downregulation inhibited the infection damage. Nrf2 was activated while NF-κB/p65 was depleted as TLR2/ TLR4 was knocked down. Activation of Nrf2 and inhibition of NF-κB resulted in decrease of TLR2/TLR4, which could retard apoptosis and inflammation induced by N.g infection. CONCLUSION: TLR2/TLR4 depletion could alleviate the N.g-infected hEECs via Nrf2/NF-kB signaling, suggesting that TLR2/TLR4 inhibitors might serve as a treatment to reduce N.g infection in human endometrial epithelia.

MiR-505 as an anti-inflammatory regulator suppresses HMGB1/NF-κB pathway in lipopolysaccharide-mediated endometritis by targeting HMGB1.

Endometritis is characterized by severe inflammation and tissue damage. It is a common clinical disease that causes infertility due to infectious diseases of the reproductive system. MicroRNAs (miRNAs) are the current focus of research on the regulation of the inflammatory process and play a vital role in various inflammatory diseases. The highly conserved miR-505 regulates the mechanism of lipopolysaccharide (LPS) induced endometritis, but the extent to which pro-inflammatory genes are activated remains unclear. The results of this study showed that the expression of miR-505 was significantly down-regulated in mouse endometritis tissue and LPS-stimulated BEND cells. The study also showed that overexpression of miR-505 significantly suppressed the production of the pro-inflammatory cytokines IL-1ß, IL-6 and TNF-α, and this effect was reversed by inhibiting the expression of miR-505. Moreover, miR-505 inhibited the expression of HMGB1 by targeting its 3'-UTR, thereby inhibiting the activation of HMGB1/NF-κB signalling. Taken together, the results of this study further confirmed that miR-505, as an anti-inflammatory agent, regulates the activation of the HMGB1/NF-κB signalling pathway through negative feedback.

Chronic endometritis and reproductive failure: Role of syndecan-1.

Chronic endometritis (CE) is an unusual inflammatory condition characterized by endometrial plasmacyte infiltration. It has a high prevalence in women with reproductive failure. Because of its characteristic localization patterns and molecular functions, syndecan-1 has been identified as a biomarker of plasmacyte, and syndecan-1 immunohistochemistry (IHC) becomes the most dependable diagnostic method for CE. In this review, we discuss the association between CE and reproductive failure, the clinicopathological characterization of CE, the function and expression of syndecan-1, the progress of syndecan-1 IHC in the diagnosis of CE, and the prediction of reproductive outcome.

Innate Lymphoid Cells Are Required for Endometrial Resistance to Chlamydia trachomatis Infection.

In some women, sexually transmitted Chlamydia trachomatis may ascend to infect the endometrium, leading to pelvic inflammatory disease. To identify endometrial innate immune components that interact with Chlamydia, we introduced C. trachomatis into mouse endometrium via transcervical inoculation and compared the infectious yields in mice with and without immunodeficiency. Live C. trachomatis recovered from vaginal swabs or endometrial tissues peaked on day 3 and then declined in all mice with or without deficiency in adaptive immunity, indicating a critical role for innate immunity in endometrial control of C. trachomatis infection. Additional knockout of interleukin 2 receptor common gamma chain (IL-2Rγc) from adaptive immunity-deficient mice significantly compromised the endometrial innate immunity, demonstrating an important role for innate lymphoid cells (ILCs). Consistently, deficiency in IL-7 receptor alone, a common gamma chain-containing receptor required for ILC development, significantly reduced endometrial innate immunity. Furthermore, mice deficient in RORγt or T-bet became more susceptible to endometrial infection with C. trachomatis, suggesting a role for group 3-like ILCs in endometrial innate immunity. Furthermore, genetic deletion of gamma interferon (IFN-γ) but not IL-22 or antibody-mediated depletion of IFN-γ from adaptive immunity-deficient mice significantly compromised the endometrial innate immunity. Finally, depletion of NK1.1+ cells from adaptive immunity-deficient mice both significantly reduced IFN-γ and increased C. trachomatis burden in the endometrial tissue, confirming that mouse ILCs contribute significantly to endometrial innate immunity via an IFN-γ-dependent effector mechanism. It will be worth investigating whether IFN-γ-producing ILCs also improve endometrial resistance to sexually transmitted C. trachomatis infection in women.