Search Results (77)

Endometriosis is a disorder characterized by the presence of endometrial tissue outside the uterus, leading to dyspareunia, chronic pelvic pain, dysuria, and infertility. The latter has been related to implantation failure associated with alterations in decidualization, a process regulated by sex hormones such as progesterone. Membrane progesterone receptor β (mPRβ) exhibits a lower expression in endometriotic tissues than in normal endometrial ones. However, the role of mPRβ in decidualization is unknown. This work aimed to investigate whether mPRβ plays a role in the decidualization of endometrial stromal cells (ESCs) derived from women with and without endometriosis. The mPR agonist OrgOD-2 induced the gene expression of key decidualization markers (insulin-like growth factor binding protein 1, prolactin, transcription factor heart and neural crest derivatives-expressed transcript 2, and fork-head transcription factor) in healthy ESCs, eutopic (uterine cavity), and ectopic (outside of the uterine cavity) ESCs from women with endometriosis. Notably, the expression of the decidualization markers was lower in endometriotic cells than in healthy endometrial ones. An siRNA mediated knockdown of mPRβ reduced the expression of decidualization-associated genes in ESCs treated with a decidualization stimuli, regardless of whether cells were derived from healthy women or those with endometriosis. Our data suggest that progesterone, through mPRβ activation, regulates the decidualization process in endometrial stromal cells from women with and without endometriosis. Full article

Background: Endometriosis is a chronic gynecological condition marked by ectopic endometrial-like tissue, leading to inflammation, pain, and infertility. Diagnosis is often delayed by up to 10 years. Identifying non-invasive biomarkers could facilitate earlier detection. MicroRNAs, known for their stability in biological fluids and role in disease processes, have emerged as potential diagnostic tools. This pilot study investigated whether serum miRNA profiling can differentiate endometriosis from other causes of chronic pelvic pain. Methods: Serum samples from 52 patients (36 with laparoscopically confirmed endometriosis and 16 controls) treated for chronic pelvic pain at a University Endometriosis Centre were analyzed. High-throughput miRNA sequencing was performed. Feature selection reduced 4285 miRNAs to the 20 most informative MiRNAs. Machine learning models, including logistic regression, decision tree, random forest, and support vector machine, were trained and evaluated. Results: Among the tested machine learning models, support vector machine achieved the best overall performance (accuracy 0.71, precision 0.80), while logistic regression and random forest showed the highest AUC values (0.84 and 0.81, respectively), indicating strong diagnostic potential of serum miRNA profiling. Conclusions: This study demonstrates the feasibility of using serum miRNA profiling combined with machine learning for the non-invasive classification of endometriosis. The identified miRNA signature shows strong diagnostic potential and could contribute to earlier and more accurate detection of the disease. Full article

Endometriosis is a chronic inflammatory disease characterized by the presence of ectopic endometrial tissue, mainly in the pelvic cavity. It primarily affects women of reproductive age and is associated with significant morbidity, particularly chronic pelvic pain and infertility. Despite its high prevalence, diagnosis is often delayed, contributing to prolonged suffering and increased healthcare burden. This review examines the management of endometriosis in Primary Care, focusing on clinical presentation, risk factors, diagnostic approaches, and therapeutic options. A comprehensive bibliographic search was conducted using PubMed, Scopus, and Uptodate, including evidence-based clinical guidelines and literature up to January 2025. Women diagnosed with endometriosis in Primary Care are typically of reproductive age, with symptoms including dysmenorrhea, dyspareunia, and abnormal uterine bleeding. Risk factors include early menarche, low birth weight, short menstrual cycles, and family history. Transvaginal ultrasound is the recommended first-line imaging tool. Treatment includes analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), and hormonal therapies such as combined oral contraceptives or progestins. Non-pharmacological interventions, including dietary modifications and psychological support, are also relevant. Early identification in Primary Care is key to improving out-comes. Enhancing awareness among healthcare providers and promoting multidisciplinary management are essential to optimize care and reduce diagnostic delays. Full article

Endometriosis (EMS) is a long-term inflammatory disease. It represents one of the most prevalent gynecological conditions, impacting an estimated 5% of reproductive women. Therefore, endometriosis contributes to substantial worldwide health challenges and healthcare costs. In EMS disease, endometrial glandular and stromal tissues are abnormally located outside the uterus. Similarly to the natural endometrium, these tissues grow and proliferate in response to estrogen-dependent signals. The pain and limited effectiveness of treatments are often linked to the inflammatory reaction triggered by EMS-associated ectopic tissue. This is especially amplified during the peaks of estrogen release that occur as the menstrual cycle transitions from the proliferative phase to ovulation. Maintaining the integrity of the mucosal lining, defending against pathogenic insults, and controlling physiological processes are all made possible by a healthy, balanced state of gut biomass. Additionally, numerous intestinal bacteria have been discovered to possess estrogen-metabolizing enzymes, which affect the estrobolome and, consequently, influence estrogen-related disorders. Therefore, there is increasing interest in understanding the role of microbiota and the estrobolome in endometriosis pathogenesis. This review will focus on the role of microbiota and the impact of estrobolome alterations in endometriosis pathogenesis. Full article

Endometriosis is a clinical entity affecting up to 10% of women of reproductive age, characterized by ectopic endometrial tissue outside the uterine cavity. While extrapelvic endometriosis has been documented, pancreatic endometriosis remains extremely rare and poses significant diagnostic challenges due to its similarity to other pancreatic diseases. At the same time, splenic mesothelial cysts are also rare and typically benign. This report presents a unique case of pancreatic endometriosis coexisting with a splenic mesothelial cyst in a 31-year-old woman. The patient presented to the emergency department with complaints of persistent epigastric and low back pain. She noted having similar symptoms approximately a year prior. Her past medical history was otherwise unremarkable, and there was no known family history of pancreatic disease or neoplasms. Initial imaging revealed a 3.8 cm cystic lesion in the pancreatic tail, with features suggestive of mucinous cystadenoma. Following clinical evaluation and confirmation of the cyst’s nature through endoscopic ultrasound-guided biopsy, the patient subsequently underwent laparoscopic distal pancreatectomy and splenectomy due to worsening symptoms. Gross examination revealed a multilocular pancreatic cyst with a smooth, hemorrhagic wall. Microscopic analysis showed the cyst to be lined by cuboidal to columnar epithelium, consistent with pancreatic endometriosis, confirmed by immunohistochemical staining. The spleen showed cystic formations, diagnosed as a multifaceted mesothelial cyst. In conclusion, this report is the first to document the coexistence of pancreatic endometriosis and splenic mesothelial cysts, highlighting the importance of accurate imaging and pathologic evaluation in the diagnosis of these rare conditions. Early diagnosis and surgical intervention lead to favorable outcomes, reinforcing the importance of comprehensive diagnostic strategies. Full article

Endometriosis is a complex gynecological disorder characterized by the presence of endometrial-like tissue outside the uterus, leading to chronic pain and infertility. Immunohistochemistry (IHC) serves as a vital technique for elucidating the molecular and cellular differences between ectopic endometriotic tissues and eutopic endometrium. IHC reveals significant variations in the expression of inflammatory markers, adhesion molecules, and cell cycle regulators. This literature review compiles findings from various studies that assess the role of key proteins, such as leukemia inhibitory factor (LIF), cyclooxygenase-2 (COX-2), and b-cell lymphoma 2 (BCL-2), across different menstrual phases and lesion types. Notably, elevated LIF levels and increased mast cell activity in ectopic tissues underscore the inflammatory landscape of endometriosis. Additionally, altered expression of adhesion molecules like integrins and cluster of differentiation 44 (CD44) suggests modified cellular interactions, while apoptotic markers reveal a survival advantage for ectopic cells. These insights enhance our understanding of endometriosis pathophysiology. Full article

Matrix metalloproteinases (MMPs) are key enzymes involved in the remodeling of the extracellular matrix (ECM) through the degradation of its components in a controlled endoproteolytic manner. Beyond ECM degradation, MMPs also target plasma membrane proteins implicated in signaling cascades and the progression of disease. Structurally, the catalytic function of MMPs is dependent on metal ions such as Zn²⁺. ECM remodeling by MMPs supports processes including tissue growth, morphogenesis, elongation, and adaptation to environmental changes occurring under both physiological and pathological conditions. These activities are subject to tight regulation by cellular MMP enzymes. While the current body of research has primarily centered on the functions of MMPs and their roles in cancer biology, knowledge of their involvement in vascular disease, endometriosis, fibrotic eye disease, epithelial cell differentiation, and the actions of MMP inhibitors remains comparatively sparse. This review explores the roles of MMPs in vascular disease and endometriosis, particularly as they relate to the ectopic growth of endometrial tissue. In addition, we summarize evidence regarding their contributions to disease mechanisms, with a focus on pathological progression. Due to their significant therapeutic promise in a variety of human diseases, advancing our understanding of MMP biology is likely to facilitate progress in clinical application and the development of novel interventions. This review also evaluates advances in the development and therapeutic potential of MMP inhibitors. Full article

Endometriosis is characterized by alterations of the action and control mechanisms that lead to the development of ectopic endometrial tissue. This study aimed to analyze the molecular profile of ectopic endometrium by evaluating the expression of several biomarkers [estrogen receptor (ER), progesterone receptor (PR), anti-apoptotic protein Bcl-2, and Ki-67 antigen] in relation to the stage of the disease and symptoms. A prospective study over a period of one year, consisting of 14 patients with endometriosis, was performed. All patients received laparoscopic surgical treatment for excision of the lesions and staging of the disease. The expression of the aforementioned biomarkers was assessed in the ectopic endometrial tissue from the excised lesions using immunohistochemistry to determine their expression in the glandular epithelium and stroma. The mean expression of biomarkers in the epithelial and stromal levels did not differ significantly based on disease stage. Epithelial ER expression was significantly positively correlated with stromal ER, epithelial PR, and stromal PR. Stromal ER was significantly positively correlated with epithelial PR and stromal Ki-67. Epithelial Bcl-2 was significantly positively correlated with stromal Bcl-2. Epithelial Ki-67 was significantly positively correlated with stromal Ki-67. Finally, epithelial Bcl-2 expression was significantly positively correlated with the intensity of dyspareunia. The correlation between epithelial Bcl-2 expression and the intensity of dyspareunia highlights a potential molecular link to the severity of symptoms in endometriosis. These results suggest that further exploration of these biomarkers could lead to improved understanding of their clinical implications and more personalized therapies for patients with endometriosis. Full article

Endometriosis is a complex gynecological disorder characterized by endometrial-like tissue growing outside the uterus, leading to chronic pain, infertility, and reduced quality of life. Its pathophysiology involves genetic, epigenetic, immune, and molecular factors. Theories such as retrograde menstruation, coelomic metaplasia, and stem cell involvement explain lesion formation. Endometrial mesenchymal stem cells (eMSCs) and epithelial progenitors (eEPs) contribute to lesion establishment by adhering to peritoneal surfaces, proliferating, and differentiating into ectopic tissue. Aberrant adhesion molecules, inflammatory cytokines, and molecular pathways like PI3K/Akt and Wnt/β-catenin drive proliferation, angiogenesis, and resistance to apoptosis. Elevated estrogen levels and progesterone resistance further promote lesion growth and immune evasion. Immune dysfunction, including altered macrophage activity and reduced natural killer (NK) cell function, contributes to inflammation and lesion persistence. Pain is linked to prostaglandin E2 (PGE2) and nerve infiltration, emphasizing the need for targeted pain management. Current therapies, such as GnRH agonists, suppress ovarian hormone production but face limitations in long-term efficacy and side effects. Integrating molecular insights into clinical practice may advance diagnostics and treatment, with emerging approaches focusing on molecular pathways, immune modulation, and hormonal regulation for more effective, personalized therapies. Future research should unravel the complex mechanisms driving endometriosis to improve patient outcomes. Full article

Background/Objectives: Endometriosis is a chronic gynecological disorder characterized by ectopic endometrial-like tissue. The symptoms of this disease negatively affect the patient’s quality of life, both physically and mentally. This study aims to identify key factors impacting health-related quality of life in endometriosis patients. Methods: A total of 175 patients from the Endometriosis Centre of the RWTH Aachen University Hospital were assessed using the German version of the EHP-30. The EHP is a patient self-report tool used to measure the wide range of impacts that endometriosis can have on women’s lives (affecting pain levels, leading to feelings of powerlessness and a loss of control, and affecting their emotional well-being, social support, and self-image). Multivariate linear regression and random forest analyses were performed to evaluate predictors of health-related quality of life, focusing on demographic characteristics, pain severity, endometriosis symptoms and planned procedures. Results: Key factors that have a significant negative impact on QoL include higher pain scores, dysuria, and persistent endometriosis. Higher pain scores negatively affect the EHP-30 pain (p < 0.0001), control and powerlessness (p < 0.0001) and emotional well-being (p < 0.01) scores. Dysuria has a negative effect on pain (p < 0.001), control and powerlessness (p < 0.001), emotional well-being (p < 0.05), and social support (p < 0.05). Persistent endometriosis was negatively associated with pain (p < 0.01), control and powerlessness (p < 0.01), and social support. Previous endometriosis surgery has a positive effect on the EHP-30 scores for pain, control and powerlessness, emotional well-being, and self-image (p < 0.05). Conclusions: Our study highlights the multifactorial impact of endometriosis on health-related QoL. Personalized treatments focusing on pain management, emotional support and social interventions are crucial to improve patient outcomes. Full article

This article presents a narrative review that explores the potential link between kisspeptin—a key regulator of the hypothalamic-pituitary-gonadal axis—and the pathogenesis of endometriosis. Kisspeptin plays a significant role in regulating reproductive functions by modulating the release of gonadotropin-releasing hormone (GnRH), which in turn stimulates the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Recent studies suggest that kisspeptin may also impact peripheral reproductive tissues and influence inflammatory processes involved in the development of endometriosis. Altered kisspeptin signaling has been associated with the abnormal hormonal environment observed in endometriosis, which affects menstrual cycles and ovarian function. Research indicates that women with endometriosis exhibit altered levels of kisspeptin and its receptor, KISS1R, in both eutopic and ectopic endometrial tissues, suggesting a role in disease progression, particularly in tissue invasion and lesion formation. Kisspeptin’s role in regulating matrix metalloproteinases (MMPs), enzymes essential for tissue remodeling, further supports its potential contribution to the pathophysiology of endometriosis. Moreover, kisspeptin-based therapeutic strategies are currently under investigation, with the aim of providing targeted treatments that reduce the side effects commonly associated with existing therapies. Despite promising findings, further research is needed to fully understand the mechanisms by which kisspeptin influences endometriosis. Full article

Background/Objectives: Adenomyosis is a benign condition where ectopic endometrial glandular tissue is found within the uterine myometrium. Its impact on women’s reproductive outcomes is substantial, primarily due to defective decidualization, impaired endometrial receptivity, and implantation failure. The exact pathogenesis of the disease remains unclear, and the role of autophagy in adenomyosis and its associated infertility is not well understood. The aim of this systematic review was to conduct an exhaustive search of the literature to clarify the role of autophagy in the pathogenesis of adenomyosis. Methods: A systematic search was conducted in Medline, Embase, and Scopus databases up to the date of 20 August 2024. We included all English-written publications assessing the role of autophagy in the pathogenesis of adenomyosis. Results: Seventeen eligible articles were identified, including reviews and experimental studies involving human samples and murine models. The results showed that the role of autophagy in adenomyosis is controversial, with studies showing both increased and decreased levels of autophagy in adenomyosis. Conclusions: Autophagy plays a dual role in cell survival and death. Increased autophagy might support the survival and proliferation of ectopic endometrial cells, while decreased autophagy could prevent cell death, leading to abnormal growth. Oxidative stress may trigger pro-survival autophagy, mitigating apoptosis and promoting cellular homeostasis. Hormonal imbalances disrupt normal autophagic activity, potentially impairing endometrial receptivity and decidualization and contributing to infertility. The balance of autophagy is crucial in adenomyosis, with its dual role contributing to the complexity of the disease. Limitations: A few studies have been conducted with heterogeneous populations, limiting comparative analyses. Full article

Endometriosis is a chronic inflammatory, estrogenic disorder caused by endometrial tissue growth places other than uterine lumen, resulting in infertility and severe pelvic pain. Thymol, an extract of Thymus vulgaris, processes diverse biological properties, including anti-inflammatory, local anesthetic, decongestant, and antiseptic effects. However, the efficacy of thymol in treating endometriosis has still not been explored. Herein, this research aimed to investigate the role of thymol in the treatment of endometriosis using a murine model and Ishikawa cells. Thirty C57BL/6 mice were administered 17β-E2 (100 ng/mouse) subcutaneously for three consecutive days to induce synchronous estrus. On the last day of injection, the mice underwent surgical induction of endometriosis. After that, the mice were divided into three groups, i.e., Control (CTRL), Thymol 30 mg/kg and Thymol 60 mg/kg, receiving oral administration of either saline or thymol (30 mg/kg/d or 60 mg/kg/d, as 0.1 mL/kg/d, respectively) for a three-week duration. Each group consisted of ten mice and was evenly divided into estrus and diestrus according to the vaginal cytology on the last day of treatment. Thymol significantly (p < 0.05) reduced the weight and volume of ectopic tissue, hindered cell proliferation, and stimulated apoptosis compared to the CTRL group. Additionally, in the thymol-treated group, the levels of pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6, as well as the numbers of neutrophils and macrophages, were significantly (p < 0.05) decreased. Moreover, a novel role of thymol in rebalancing estrogen and progesterone (E₂-P₄) signaling was explored, and it was distributed in the ectopic endometrium. Next, the role of thymol on Ishikawa cells was determined. The results demonstrated that thymol significantly (p < 0.05) suppressed the E₂-induced proliferation of Ishikawa cells. Furthermore, molecular docking analyses suggested that thymol potentially binds to ESR1-like estrogens, indicating its antagonistic activity against estrogens. The estrogen receptor 1 (ESR1) and its target gene expression exhibited significant (p < 0.05) downregulation, while progesterone receptor (PGR) and target genes were markedly (p < 0.05) upregulated following thymol treatment in the ectopic endometrium. Most importantly, our data revealed the minimal impact of thymol treatment on the eutopic endometrium and its crucial role in supporting pregnancy, thus indicating the safety of thymol in treating endometriosis. Overall, our study suggests that thymol holds promising therapeutic implications for endometriosis by virtue of its anti-inflammatory properties and ability to antagonize estrogen activity. Full article

(1) Background: Endometriosis is a highly prevalent gynecological disease affecting 10% of women of reproductive age worldwide. miRNAs may play a role in endometriosis, though their exact function remains unclear. This study aimed to identify differentially expressed miRNAs in endometriosis and study their functions in the disease. (2) Methods: Endometrial tissue was collected from women with endometriosis (n = 15) and non-endometriosis controls (n = 17). Dysregulated miRNAs were identified through small RNA-sequencing, and their biological significance was explored by target gene prediction and pathway analysis. Selected miRNAs were examined in paired ectopic endometriomas and eutopic endometrium (n = 10) using qRT-PCR. Their roles in cell migration and proliferation were further examined in vitro using functional assays. To identify potential target genes, we performed mRNA sequencing on transfected cells and the endometrioma cohort. (3) Results: We identified 14 dysregulated miRNAs in the eutopic endometrium of women with endometriosis compared to endometrial tissue from women without endometriosis. Pathway analysis indicated enrichment in cell migration and proliferation-associated pathways. Further ex vivo studies of miR-193b-5p and miR-374b-5p showed that both miRNAs were upregulated in endometrioma. Overexpression of these two miRNAs in vitro inhibited cell migration, and mRNA sequencing revealed several migration-related genes that are targeted by these miRNAs. (4) Conclusions: Our study identified two key endometrial miRNAs that may be involved in the pathogenesis of endometriosis by regulating cell migration. Full article

Adenomyosis involves the infiltration of endometrial glands and stroma deep into the uterine tissue, causing disruption to the endometrial–myometrial interface (EMI). The role of interleukin-17 (IL-17) has been extensively studied in endometriosis, but its involvement in adenomyosis remains unclear. This study aimed to investigate the expression of IL-17 in eutopic and ectopic endometrium (adenomyosis) of individuals with adenomyosis at the level of EMI. Paired tissues of eutopic endometrium and adenomyoma were collected from 16 premenopausal women undergoing hysterectomy due to adenomyosis. The IL-17 system was demonstrated in paired tissue samples at the level of EMI by the immunochemistry study. Gene expression levels of IL-17A and IL-17 receptor (IL-17R) were assessed through quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). Comparative gene transcript amounts were calculated using the delta-delta Ct method. By immunohistochemical staining, CD4, IL-17A, and IL-17R proteins were detected in both eutopic endometrium and adenomyosis at the level of EMI. IL-17A and IL-17R were expressed mainly in the glandular cells, and the expression of both IL-17A and IL-17R was found to be stronger in adenomyosis than in endometrium. 3-Diaminobenzidine (DAB) staining revealed greater IL-17A expression in adenomyosis compared to eutopic endometrium. Quantitative RT-PCR showed 7.28-fold change of IL-17A and 1.99-fold change of IL-17R, and the fold change level of both IL-17A and IL-17R is significantly higher in adenomyosis (IL-17A: p = 0.047, IL-17R: p = 0.027) versus eutopic endometrium. We found significantly higher IL-17 levels in adenomyosis compared to eutopic endometrium at the level of EMI. The results showed that the IL-17 system may play a role in adenomyosis. Full article