Proangiogenic properties of complement protein C1q can contribute to endometriosis.

Endometriosis (EM) is defined as the engraftment and proliferation of functional endometrial-like tissue outside the uterine cavity, leading to a chronic inflammatory condition. While the precise etiology of EM remains elusive, recent studies have highlighted the crucial involvement of a dysregulated immune system. The complement system is one of the predominantly altered immune pathways in EM. Owing to its involvement in the process of angiogenesis, here, we have examined the possible role of the first recognition molecule of the complement classical pathway, C1q. C1q plays seminal roles in several physiological and pathological processes independent of complement activation, including tumor growth, placentation, wound healing, and angiogenesis. Gene expression analysis using the publicly available data revealed that C1q is expressed at higher levels in EM lesions compared to their healthy counterparts. Immunohistochemical analysis confirmed the presence of C1q protein, being localized around the blood vessels in the EM lesions. CD68+ macrophages are the likely producer of C1q in the EM lesions since cultured EM cells did not produce C1q in vitro. To explore the underlying reasons for increased C1q expression in EM, we focused on its established pro-angiogenic role. Employing various angiogenesis assays on primary endothelial endometriotic cells, such as migration, proliferation, and tube formation assays, we observed a robust proangiogenic effect induced by C1q on endothelial cells in the context of EM. C1q promoted angiogenesis in endothelial cells isolated from EM lesions (as well as healthy ovary that is also rich in C1q). Interestingly, endothelial cells from EM lesions seem to overexpress the receptor for the globular heads of C1q (gC1qR), a putative C1q receptor. Experiments with siRNA to silence gC1qR resulted in diminished capacity of C1q to perform its angiogenic functions, suggesting that C1q is likely to engage gC1qR in the pathophysiology of EM. gC1qR can be a potential therapeutic target in EM patients that will disrupt C1q-mediated proangiogenic activities in EM.

Exploring the link: Systemic immune-inflammation index as a marker in endometriosis-Insights from the NHANES 2001-2006 cross-sectional study.

OBJECTIVE: The systemic immuno-inflammatory index (SII), a novel immune marker of inflammation, has not been previously associated with endometriosis. The objective of this research is to explore the link between SII and the occurrence of endometriosis. METHODS: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 2001 to 2006, we screened and extracted relevant information from the population. Participants missing data on either SII or endometriosis were excluded. We divided the remaining cohort into quartiles based on SII levels: Q1 (SII < 249, n = 848), Q2 (249 ≤ SII < 604.55, n = 847), Q3 (604.55 ≤ SII < 825.35, n = 847), and Q4 (SII ≥ 852.35, n = 848). Multiple linear regression and smooth curve fitting techniques, were to evaluate the non-linear association between SII and endometriosis. RESULTS: The study included 3,390 adults aged 20 to 55. Multiple linear regression analysis revealed a significant positive correlation between SII and endometriosis [3.14, 95% CI (2.22, 4.45), P < 0.01]. This correlation was consistent across subgroups defined by marital status, poverty income ratio, BMI, alcohol consumption, and age at first menstrual period. However, the relationship between SII and endometriosis was significantly modified by age, education, and history of pregnancy in the stratified analyses. The curve fitting indicated an S-shaped curve, with an inflection point at SII = 1105.76. CONCLUSION: The SII may serve as a predictive marker for endometriosis risk among women in the United States, offering a potentially simple and cost-effective approach. However, given the cross-sectional design of this investigation, further validation in prospective studies is necessary.

TIM-3 Expression in Endometriosis.

PROBLEM: Endometriosis is a prevalent chronic gynecological disease linked to immune dysfunction. The protein T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) plays a crucial role in immune system balance. Malfunction of TIM-3 may result in excessive immune activation and inflammatory tissue damage. Given TIM-3's established role in the development of cancer and autoimmune diseases, we decided to study its role in women suffering from endometriosis. STUDY METHOD: We included a total of 62 female patients, all of whom had undergone laparoscopic surgery. Of these, 47 had endometriosis and 15 did not. During surgery, we collected peritoneal fluid (PF) and peripheral blood (PB) samples from every patient for analysis using flow cytometry. To mark the samples, we used a panel of monoclonal antibodies and examined TIM-3 expression in their immune cells. RESULTS: Endometriosis patients in PB demonstrated a significantly lower percentage of CD56+ T cells with TIM-3 expression. As endometriosis progressed through its stages, this expression lessened. This decrease was particularly notable in women with stage III/IV endometriosis. Additionally, both women diagnosed with intestinal endometriosis and those with recent endometriosis diagnoses showed a significantly reduced percentage of CD56+ T cells expressing TIM-3. CONCLUSIONS: Patients with endometriosis exhibit diminished TIM-3 expression within circulating T cells. This warrants further investigation to discern whether it contributes to the progression of endometriosis, potentially through the amplification of autoreactive T cells and inflammation.

Immunomodulation in Endometriosis: Investigating the interrelationship between VISTA expression and Escherichia.Shigella-Associated metabolites.

AIMS: Endometriosis is characterized by an abnormal immune microenvironment. Despite the extensive use of immune therapies, the application of immune checkpoint inhibitors in endometriosis lacks confidence due to the instability of preclinical research data. This study aims to elucidate the regulation of the immune inhibitory checkpoint VISTA and its effects on T cells from the perspective of microbiota and metabolism. MAIN METHODS: We divided endometriosis patients into high and low groups based on the expression levels of VISTA in lesion tissues. We collected peritoneal fluid samples from these two groups and performed 16 s RNA sequencing and metabolomics analysis to investigate microbial diversity and differential metabolites. Through combined analysis, we identified microbial-associated metabolites and validated their correlation with VISTA and CD8 + T cells using ELISA and immunofluorescence. In vitro experiments were conducted to confirm the regulatory relationship among these factors. KEY FINDINGS: Our findings revealed a distinct correlation between VISTA expression and the microbial colony Escherichia.Shigella. Moreover, we identified the metabolites LTD4-d5 and 2-n-Propylthiazolidine-4-carboxylic acid as being associated with both Escherichia.Shigella and VISTA expression. In vitro experiments confirmed the inhibitory effects of these metabolites on VISTA expression, while they demonstrated a positive regulation of CD8 + T cell infiltration into endometriotic lesions. SIGNIFICANCE: This study reveals the connection between microbial diversity, metabolites, and VISTA expression in the immune microenvironment of endometriosis, providing potential targets for therapeutic interventions.

Immune Checkpoints in Endometriosis-A New Insight in the Pathogenesis.

Endometriosis (EMS) is an oestrogen-dependent, chronic disease affecting women of a reproductive age. One of the important factors involved in the development of this disease is the complex disorders associated with the functioning of the immune system. Recent evidence has shown that EMS development is associated with changes in systemic and local immunity, including functional disturbances of effector and antigen-presenting cells. One of the reasons for immune imbalance can be the improper expression of immune checkpoints (ICPs). ICPs and their ligands are responsible for maintaining self-tolerance and the modulation of the initiation, duration, and magnitude of the immune response of effector cells in normal tissues to avoid tissue damage. Considering the complex nature of co-stimulatory or co-inhibitory ICPs and the signalling between effector cells and APCs, we hypothesise that changes in cells' activity caused by ICPs may lead to serious immune system disturbances in patients with endometriosis. Moreover, both upregulation and downregulation in the expression of ICPs may be implicated in this process, including the reduced activity of effector cells against endometrial implants and disturbances in the antigen-presenting process. In this narrative review, we discuss, for the first time, key findings from the emerging literature, describing the associations between ICPs and their possible implication in the pathogenesis of endometriosis.

Causal association of immune cells and endometriosis: a Mendelian randomization study.

Objective: To investigate the causal effect of immune cells on endometriosis (EMS), we performed a Mendelian randomization analysis. Methods: Mendelian randomization (MR) uses genetic variants as instrumental variables to investigate the causal effects of exposures on outcomes in observational data. In this study, we conducted a thorough two-sample MR analysis to investigate the causal relationship between 731 immune cells and endometriosis. We used complementary Mendelian randomization (MR) methods, including weighted median estimator (WME) and inverse variance weighted (IVW), and performed sensitivity analyses to assess the robustness of our results. Results: Four immune phenotypes have been found to be significantly associated with the risk of developing EMS: B cell %lymphocyte (WME: OR: 1.074, p = 0.027 and IVW: OR: 1.058, p = 0.008), CD14 on Mo MDSC (WME: OR: 1.056, p =0.021 and IVW: OR: 1.047, p = 0.021), CD14+ CD16- monocyte %monocyte (WME: OR: 0.947, p = 0.024 and IVW: OR: 0.958, p = 0.011), CD25 on unsw mem (WME: OR: 1.055, p = 0.030 and IVW: OR: 1.048, p = 0.003). Sensitivity analyses confirmed the main findings, demonstrating consistency across analyses. Conclusions: Our MR analysis provides compelling evidence for a direct causal link between immune cells and EMS, thereby advancing our understanding of the disease. It also provides new avenues and opportunities for the development of immunomodulatory therapeutic strategies in the future.

The PD-1/PD-L1 Gateway: Peripheral Immune Regulation in the Pathogenesis of Endometriosis.

Endometriosis is a chronic inflammatory disease characterized by the presence of endometrial-like tissue outside the uterine cavity, causing pain and infertility. Despite the rather unclear etiopathogenesis, recent studies suggest the involvement of the immune system in the development and progression of endometriosis. The role of the PD-1/PD-L1 axis in the modulation of the immune response in this disease seems to be particularly interesting. This preliminary study aimed to investigate the expression of PD-1 and PD-L1 on T and B lymphocytes in peripheral blood in patients with endometriosis to assess their potential impact on disease progression. Our study involved peripheral blood samples from 80 patients diagnosed with endometriosis and 20 healthy women as a control group were analyzed. Flow cytometry was used to assess the expression of PD-1 and PD-L1 on T and B lymphocytes, and enzyme-linked immunosorbent assays were used to assess their soluble forms in serum and peritoneal fluid.in our research we observe significantly higher expression of PD-1 and PD-L1 on T and B lymphocytes was found in patients with endometriosis compared to the control group. Higher expression of both tested molecules correlated with the stage of endometriosis. The results of our preliminary studies indicate a potential role of the PD-1/PD-L1 axis in the modulation of the immune response in endometriosis. Modified expression of these proteins may contribute to immune evasion by ectopic tissues, supporting their survival and proliferation. These findings suggest that targeting PD-1/PD-L1 could be explored as a therapeutic option for the treatment of endometriosis, though further research with larger sample sizes is necessary to confirm these results and clarify the role of PD-1/PD-L1 in the pathogenesis of the disease.

Immune Dysregulation in Endometriomas: Implications for Inflammation.

The most common manifestation of endometriosis, a condition characterized by the presence of endometrial-like tissue outside of the uterus, is the endometrioma, a cystic ovarian lesion. It is a commonly occurring condition associated with chronic pelvic pain exacerbated prior to and during menstruation, as well as infertility. The exact pathomechanisms of the endometrioma are still not fully understood. Emerging evidence suggests a pivotal role of immune dysregulation in the pathogenesis of endometriomas, primarily influencing both local and systemic inflammatory processes. Among the factors implicated in the creation of the inflammatory milieu associated with endometriomas, alterations in both serum and local levels of several cytokines stand out, including IL-6, IL-8, and IL-1ß, along with abnormalities in the innate immune system. While numerous signaling pathways have been suggested to play a role in the inflammatory process linked to endometriomas, only NF-κB has been conclusively demonstrated to be involved. Additionally, increased oxidative stress, both resulting from and contributing to endometriomas, has been identified as a primary driver of both systemic and local inflammation associated with the condition. This article reviews the current understanding of immune dysfunctions in the endometrioma and their implications for inflammation.

Immune micro-environment analysis and drug screening for ovarian endometriosis.

BACKGROUND: Patients of ovary endometriosis have an abnormal immune micro-environment, leading to endometrial tissue that from retrograde menstruation evade immune surveillance and subsequently develop into ectopic lesions. OBJECTIVE: This study aims to elucidate the crucial immune cells and molecular pathways that are associated with an aberrant immune micro-environment of endometriosis. METHOD: In this study, we identified differentially expressed genes between ovarian ectopic endometrial tissue (OVE) and eutopic endometrial tissue from patients with endometriosis (PE) and non-endometriosis patients (CON) by analyzing the mRNA sequencing data. Additionally, we used WGCNA(Weighted Gene Co-expression Network Analysis) to screen for key genes related to immune cell infiltration and compared the sub-types of infiltrating immune cells using CIBERSORT(cell-type identification by estimating relative subsets of RNA transcript). Subsequently, we conducted a single-cell analysis on the identified key genes. Furthermore, we analyzed potential drugs suitable for ovarian endometriosis treatment using pRRophertic. RESULTS: Seven key genes associated with immune cell infiltration were screened out. The expression of these genes in OVE was significantly lower than that in PE and CON. These key genes were mainly enriched in the NK cell-mediated cytotoxicity pathway, especially for CD16 + CD56dim NK. Moreover, NK cells infiltration in ovarian endometriosis was significantly reduced compared with PE and CON, while M2 macrophage shown the opposite. Results of the single-cell analysis showed that the expression of the seven key genes in NK cells and monocyte-macrophages in OVE was significantly lower than that in PE or CON. Additionally, we identified potential drugs suitable for ovarian endometriosis treatment. CONCLUSION: The decreased infiltration of NK cells and increased infiltration of M2 macrophages contribute to the evasion of immune surveillance against endometrial tissue, promoting the progression of OVE. Therefore, potential strategies for the treatment of OVE include increasing NK cell activation and decreasing M2 macrophage polarization.

Foxp3+CD39+CD73+ regulatory T-cells are decreased in the peripheral blood of women with deep infiltrating endometriosis.

Endometriosis's pathophysiology remains incompletely understood, with evidence pointing towards a dysregulated immune response. Regulatory T (Treg) cells, pivotal in maintaining self-tolerance, may facilitate the survival of ectopic endometrial cells within the abdominal cavity, thereby contributing to endometriosis development. This study aimed to assess the prevalence of CD39+CD73+ suppressor Treg cell subsets in the peripheral blood of endometriosis patients. This research focuses on the pivotal role of regulatory T-cells (Tregs), which are essential for maintaining immune tolerance and preventing autoimmune diseases. A case-control study was conducted, including 32 women diagnosed with endometriosis and 22 control subjects. The frequency of peripheral blood CD39+CD73+ suppressor Treg cells was quantified using flow cytometry. No significant differences were observed in the frequency of CD3+CD4+CD25High cells (Median [M]: 10.1; Interquartile Range [IQR]: 6.32‒18.3 vs. M: 9.72; IQR: 6.22-19.8) or CD3+CD4+CD25HighCD39+Foxp3+ cells (M: 31.1; IQR: 19.7-44.0 vs. M: 30.55; IQR: 18.5-45.5) between controls and patients. However, a significantly lower frequency of CD3+CD4+CD25HighCD39+CD73+ cells was observed in the endometriosis group compared to controls (M: 1.98; IQR: 0.0377-3.17 vs. M: 2.25; IQR: 0.50-4.08; p = 0.0483), suggesting a reduction in systemic immune tolerance among these patients. This finding highlights the potential role of CD39 and CD73 expression on Treg cells as biomarkers for assessing disease severity and progression. Furthermore, elucidating the mechanisms driving these alterations may unveil new therapeutic strategies to restore immune equilibrium and mitigate endometriosis symptoms.

Identification of diagnostic markers related to inflammatory response and cellular senescence in endometriosis using machine learning and in vitro experiment.

OBJECTIVE: To understand the association between chronic inflammation, cellular senescence, and immunological infiltration in endometriosis. METHODS: Datasets from GEO comprising 108 endometriosis and 97 healthy human samples and the human endometrial stromal cell. Differentially expressed genes were identified using Limma and WGCNA. Inflammatory response-related subtypes were constructed using consensus clustering analysis. The CIBERSORT algorithm and correlation analyses assessed immune cell infiltration. LASSO, SVM-RFE, and RF identified diagnostic genes. Functional enrichment analysis and multifactor regulatory networks established functional effects. Nomograms, internal and external validations, and in vitro experiments validated the diagnostic genes. RESULTS: Inflammatory response subtypes were highly correlated with the immune activities of B and NK cells. Sixteen genes were associated with inflammatory response and cellular senescence and six diagnostic genes (NLK, RAD51, TIMELESS, TBX3, MET, and BTG3) were identified. The six diagnostic gene models had an area under the curve of 0.828 and their expression was significantly downregulated in endometriosis samples. Low expression of NLK and BTG3 promoted the proliferation, migration, and invasion of endometriotic cells. CONCLUSIONS: Inflammatory response subtypes were successfully constructed for endometriosis. Six diagnostic genes related to inflammatory response and cellular senescence were identified and validated. Our study provides novel insights for inflammatory response in endometriosis and markers for endometriosis diagnosis and treatment.

Potential shared pathogenic mechanisms between endometriosis and inflammatory bowel disease indicate a strong initial effect of immune factors.

Introduction: Over the past decades, immune dysregulation has been consistently demonstrated being common charactoristics of endometriosis (EM) and Inflammatory Bowel Disease (IBD) in numerous studies. However, the underlying pathological mechanisms remain unknown. In this study, bioinformatics techniques were used to screen large-scale gene expression data for plausible correlations at the molecular level in order to identify common pathogenic pathways between EM and IBD. Methods: Based on the EM transcriptomic datasets GSE7305 and GSE23339, as well as the IBD transcriptomic datasets GSE87466 and GSE126124, differential gene analysis was performed using the limma package in the R environment. Co-expressed differentially expressed genes were identified, and a protein-protein interaction (PPI) network for the differentially expressed genes was constructed using the 11.5 version of the STRING database. The MCODE tool in Cytoscape facilitated filtering out protein interaction subnetworks. Key genes in the PPI network were identified through two topological analysis algorithms (MCC and Degree) from the CytoHubba plugin. Upset was used for visualization of these key genes. The diagnostic value of gene expression levels for these key genes was assessed using the Receiver Operating Characteristic (ROC) curve and Area Under the Curve (AUC) The CIBERSORT algorithm determined the infiltration status of 22 immune cell subtypes, exploring differences between EM and IBD patients in both control and disease groups. Finally, different gene expression trends shared by EM and IBD were input into CMap to identify small molecule compounds with potential therapeutic effects. Results: 113 differentially expressed genes (DEGs) that were co-expressed in EM and IBD have been identified, comprising 28 down-regulated genes and 86 up-regulated genes. The co-expression differential gene of EM and IBD in the functional enrichment analyses focused on immune response activation, circulating immunoglobulin-mediated humoral immune response and humoral immune response. Five hub genes (SERPING1、VCAM1、CLU、C3、CD55) were identified through the Protein-protein Interaction network and MCODE.High Area Under the Curve (AUC) values of Receiver Operating Characteristic (ROC) curves for 5hub genes indicate the predictive ability for disease occurrence.These hub genes could be used as potential biomarkers for the development of EM and IBD. Furthermore, the CMap database identified a total of 9 small molecule compounds (TTNPB、CAY-10577、PD-0325901 etc.) targeting therapeutic genes for EM and IBD. Discussion: Our research revealed common pathogenic mechanisms between EM and IBD, particularly emphasizing immune regulation and cell signalling, indicating the significance of immune factors in the occurence and progression of both diseases. By elucidating shared mechanisms, our study provides novel avenues for the prevention and treatment of EM and IBD.

Stress, pain, anxiety, and depression in endometriosis-Targeting glial activation and inflammation.

Endometriosis (EM) is a gynecological inflammatory disease often accompanied by stress, chronic pelvic pain (CPP), anxiety, and depression, leading to a diminished quality of life. This review aims to discuss the relationship between systemic and local inflammatory responses in the central nervous system (CNS), focusing on glial dysfunctions (astrocytes and microglia) as in critical brain regions involved in emotion, cognition, pain processing, anxiety, and depression. The review presents that EM is connected to increased levels of pro-inflammatory cytokines in the circulation. Additionally, chronic stress and CPP as stressors may contribute to the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, depleting the production of inflammatory mediators in the circulatory system and the brain. The systemic cytokines cause blood-brain barrier (BBB) breakdown, activate microglia in the brain, and lead to neuroinflammation. Furthermore, CPP may induce neuronal morphological alterations in critical regions through central sensitization and the activation of glial cells. The activation of glial cells, particularly the polarization of microglia, leads to the activation of the NLRP3 inflammasome and the overproduction of inflammatory cytokines. These inflammatory cytokines interact with the signaling pathways involved in neural plasticity. Additionally, persistent inflammatory conditions in the brain lead to neuronal death, which is correlated with a reduced volume of key brain regions such as the hippocampus. This review highlights the involvement of glial cells in the pathogenesis of the mental comorbidities of EM (i.e., pain, anxiety, and depression) and to discuss potential therapeutic approaches for targeting the inflammation and activation of microglia in key brain regions.

The dysfunction of CD8+ T cells triggered by endometriotic stromal cells promotes the immune survival of endometriosis.

Endometriosis is defined as an oestrogen-dependent and inflammatory gynaecological disease of which the pathogenesis remains unclear. This study aimed to investigate the cellular heterogeneity and reveal the effect of CD8+ T cells on the progress of endometriosis. Three ovarian endometriosis patients were collected, and single-cell RNA sequencing (scRNA-seq) progressed and delineated the cellular landscape of endometriosis containing five cell clusters. The endometrial cells (EMCs) were the major component, of which the mesenchymal cells were preponderant and characterized with increased inflammation and oestrogen synthesis in endometriosis. The proportion of T cells, mainly CD8+ T cells rather than CD4+, was reduced in endometriotic lesions, and the cytokines and cytotoxicity of ectopic T cells were depressed. CD8+ T cells depressed the proliferation of ESCs through inhibiting CDK1/CCNB1 pathway to arrest the cell cycle and triggered inflammation through activating STAT1 pathway. Correspondingly, the coculture with ESCs resulted in the dysfunction of CD8+ T cells through upregulating STAT1/PDCD1 pathway and glycolysis-promoted metabolism reprogramming. The endometriotic lesions were larger in nude mouse models with T-cell deficiency than the normal mouse models. The inhibition of T cells via CD90.2 or CD8A antibody increased the endometriotic lesions in mouse models, and the supplement of T cells to nude mouse models diminished the lesion sizes. In conclusion, this study revealed the global cellular variation of endometriosis among which the cellular count and physiology of EMCs and T cells were significantly changed. The depressed cytotoxicity and aberrant metabolism of CD8+ T cells were induced by ESCs with the activation of STAT1/PDCD1 pathway resulting in immune survival to promote endometriosis.

The role of innate and adaptive immunity in endometriosis.

The innate and adaptive immune systems are the two key branches that determine host protection at all mucosal surfaces in human body, including the female reproductive tract. The pattern recognition receptors within the host that recognize pathogen-associated molecular patterns are expressed on the cells of the innate immune system. Rapidly reactive, theinnate immune system, responds immediately to the presence of infectious or other non-self agents, thereby launching an inflammatory response to protect the host until the activation of slower adaptive immune system. Macrophages, dendritic cells, and toll-like receptors are integral components of the innate immune system. In contrast, T-helper (Th1/Th2/Th17) cells and regulatory T (Treg) cells are the primary components of adaptive immune system. Studies showed that the growth and progression of endometriosis continue even in unilateral ovariectomized animal suggesting that besides ovarian steroid hormones, the growth of endometriosis could be regulated by innate/adaptive immune systems in pelvic environment. Recent reports demonstrated a potential role of Th1/Th2/Th17/Treg cells either individually or collectively in the initiation, maintenance, and progression of endometriosis. Herewe review the fundamental knowledge of innate and adaptive immunity and elaborate the role of innate and adaptive immunity in endometriosis based on both human and experimental data.

Research progress in rodent models of endometriosis.

Endometriosis is a common and frequent disease in gynecology; its etiology and pathogenesis are partially understood and still not clear. The construction of suitable animal models is beneficial for basic research related to the disease. Currently, rodents have the advantages of low cost, fast reproduction, easy rearing, and a similar endometrial structure to humans. Depending on the purpose of the experiment, different molding methods have their advantages. In this paper, we describe the traditional methods of constructing endometriosis rodent models, compare their advantages and disadvantages, and introduce newly developed rodent models, such as cell line injection models, pain models, genetically engineered mouse models, fluorescent tracer models, iron overload models, chemical induction models, and methods of constructing rodent models of different subtypes of endometriosis. Fertility and treatment of endometriosis rodent models are also described. This study provides a reference for researchers in the selection of animal models for pathogenesis and drug treatment studies.

Analysis of the concentration of CXCL8 chemokine and its CXCR1 and CXCR2 receptors in peritoneal fluid of women with endometriosis.

Endometriosis is an inflammatory estrogen-dependent gynecological disease characterized by the presence of endometrial tissue outside the uterine cavity. An important role in the pathogenesis of this disease is played by disorders of the immune system involving chemokines and their receptors, including the CXCL8-CXCR1/ 2 system. AIM: The aim of the study was to assess the concentration of the CXCL8 chemokine and its CXCR1 and CXCR2 receptors in the peritoneal fluid of women with endometriosis. MATERIALS AND METHODS: The study included 32 women aged 21 to 47 years with diagnosed endometriosis and a control group of 8 healthy women aged 21 to 40 years. The material for the research was the peritoneal fluid collected during the laparoscopic procedure. The concentration of chemokines was determined by ELISA tests. RESULTS: The conducted studies showed that the concentration of the CXCL8 chemokine was significantly higher in the peritoneal fluid of the studied women and depended on the clinical advancement of the disease. CONCLUSIONS: Changes in the concentration of the CXCL8 chemokine in the peritoneal fluid of women with endometriosis may indicate impaired immune response and indicate an inflammatory process within the peritoneal cavity. The demonstrated relationship between the concentration of CXCL8 and the stages of clinical advancement indicates a significant role of this chemokine in the development of the disease.

Endometriosis: An Inflammatory Disease That Requires New Therapeutic Options.

Endometriosis, defined as the presence of endometrium-like tissue outside the uterus, is estimated to affect 10% of women of reproductive age [...].

The effects of prolactin receptor blockade in a murine endometriosis interna model.

Endometriosis in an estrogen-dependent disease that is characterized by the presence of endometrial tissue outside the uterine cavity leading to pain and infertility in many affected women. Highly efficient treatment options which create a hypo-estrogenic environment can cause side effects such as hot flushes and bone mass loss that are not favorable for premenopausal women. Previous work has demonstrated that increased local or systemic prolactin seems to be involved in the pathogenesis of endometriosis. Here we examined two prolactin receptor (PRLR) blocking antibodies in a murine endometriosis interna model which relies on the induction of systemic hyperprolactinemia in female SHN mice. The severity of the disease is determined by the degree of endometrial invasion into the myometrium. In this model, endometriosis was inhibited by clinical gold standards such as progestins and anti-estrogenic approaches. PRLR blockade completely inhibited endometriosis in this mouse model to the same extent as the anti-estrogen faslodex or the GnRH antagonist cetrorelix. In contrast to cetrorelix and faslodex, the PRLR antibodies did not decrease relative uterine weights and were thus devoid of anti-estrogenic effects. We therefore hypothesize that PRLR antibodies may present a novel and highly efficient treatment option for endometriosis with a good safety and tolerability profile. Clinical studies are on the way to test this hypothesis.