Search Results (113)

Endometriosis is common and poses significant morbidity of lasting impact to young, pre-menopausal women, while ovarian cancer is a lethal gynecologic condition. Both conditions need better treatment. The human omentum is an apron of adipose tissue in the abdominopelvic cavity, the same space in which endometriosis and ovarian cancer manifest. We aim to determine molecular cues emitted by the omentum that aid the trans-coelomic spread of endometriosis and ovarian cancer in the abdomen–pelvic/peritoneal space. Endometriosis and ovarian cancer patients were prospectively recruited. Primary cell cultures of surgically-resected omentum, endometriosis and ovarian cancer were generated, and conditioned media (CM) from the omentum was derived. They were used for in vitro assays to evaluate the effect of the omentum on cell migration, angiogenesis and proliferation in endometriosis and ovarian cancer. Omental CM promoted cell migration in primary cultures of endometriosis and ovarian cancer. Omental CM contained high levels of HGF, SDF-1a, MCP-1, VEGF-A, IL-6 and IL-8. The observed cell migration was blocked by c-MET inhibition, suggesting that HGF/c-MET signaling mediates cell migration in endometriosis and ovarian cancer. Furthermore, PTTG1 was consistently upregulated in the migrated cells in both endometriosis and ovarian cancer. The omentum provides a favorable environment for trans-coelomic spread of endometriosis and ovarian cancer. HGF, c-MET and PTTG1 are potential therapeutic targets for inhibiting the abdomen–pelvic/peritoneal spread of endometriosis and ovarian cancer. Full article

Background/Objectives: Endometriosis has a marked impact on fertility, although the mechanisms behind this relationship remain poorly understood, particularly in cases without significant anatomical distortions or in the context of ovarian endometriomas. This study aimed to investigate the effect of peritoneal endometriosis on ovarian function by assessing ovarian reserve and apoptosis. Methods: Peritoneal endometriosis was surgically induced in Sprague Dawley rats through the autotransplantation of uterine fragments onto the bowel mesothelium. One month post-surgery, ovarian structures were counted, follicle and corpora lutea apoptosis was evaluated by TUNEL, and apoptotic-related protein expression in ovaries was assessed by Western blot. Additionally, a co-culture system using 12Z endometriotic and KGN granulosa cell lines was utilized to evaluate gene expression by RT-qPCR. Results: Rats with peritoneal endometriosis exhibited a significant reduction in ovarian structures characterized by a low number of total follicles, particularly primordial, primary, preantral, and late-antral follicles. Consistently, AMH protein expression was decreased in ovaries in the presence of endometriosis. In addition, this disease led to a significant increase in late-antral follicles that were TUNEL-positive and in the number of apoptotic cells in corpora lutea, indicating higher apoptosis in endometriosis ovaries. Concomitantly, the altered expression of apoptosis-related proteins was observed, with increased procaspase 3 and decreased BCL-2 expression. In addition, KGN granulosa cells co-cultured with 12Z endometriotic cells displayed reduced KITLG mRNA expression and increased AMHR2 mRNA expression. Conclusions: Peritoneal endometriosis significantly impairs ovarian health by disrupting folliculogenesis, reducing ovarian reserve, and increasing apoptosis, potentially accelerating ovarian aging and contributing to infertility. These results underscore the need for further research to identify the molecular pathways involved and to develop targeted therapeutic strategies. Full article

Spontaneous rupture of the utero-ovarian vessels is an exceptionally rare but potentially life-threatening condition, especially in the case of non-pregnant women with a history of complex gynecological conditions. We report the case of a 45-year-old woman presenting with severe abdominal pain and hemoperitoneum, 15 years after surgical eradication of stage IV endometriosis. Diagnostic imaging revealed significant free fluid and vascular disruption near the uterus. Emergency laparotomy confirmed blood in the peritoneal cavity and identified a rupture of the left paracervical vessels. This case underscores the critical role of timely surgical intervention and the challenges of diagnosing spontaneous vascular rupture in the context of chronic conditions such as endometriosis and fibromyalgia. A review of the literature revealed very limited cases with similar presentations, emphasizing the rarity of such vascular events, although without active endometriotic lesions. This report highlights the importance of considering spontaneous vascular rupture in differential diagnoses for acute abdominal pain with hemoperitoneum. Advanced imaging and multidisciplinary management are pivotal in ensuring favorable outcomes. Full article

Endometriosis is a common gynecological condition affecting approximately 10% of women of reproductive age, characterized by the abnormal presence of endometrial-like tissue outside the uterus. Although endometriosis was first described over 300 years ago, its underlying mechanisms remain poorly understood, and accurate, prompt diagnosis continues to be challenging. Currently, there is a lack of effective, non-invasive diagnostic methods, and available treatments often come with significant side effects and high recurrence rates. This has spurred interest in investigating the role of pro- and anti-inflammatory molecules, particularly cytokines, in endometriosis, as these molecules play a key role in its progression by influencing cell growth and differentiation. Previous studies suggest that various cytokines could serve as potential biomarkers for diagnosing endometriosis, as they are detectable in both serum and peritoneal fluid. This review provides an overview of the expression, origin, function, and regulation of specific cytokines in endometriosis, along with a brief discussion on their potential clinical implications for diagnosis. Due to the complexity of endometriosis, a panel of multiple biomarkers may ultimately be necessary for accurate diagnosis. It is essential to consider factors such as patient selection, sample collection, and analytical variability when initiating or evaluating biomarker studies. Full article

This study aimed to identify unique characteristics in the peripheral blood mononuclear cells (PBMCs) of endometriosis patients and develop a non-invasive early diagnostic tool. Using single-cell RNA sequencing (scRNA-seq), we constructed the first single-cell atlas of PBMCs from endometriosis patients based on 107,964 cells and 25,847 genes. Within CD16⁺ monocytes, we discovered JUP as a dysregulated gene. To assess its diagnostic potential, we measured peritoneal fluid (PF) and serum JUP levels in a large cohort of 199 patients including 20 women with ovarian cancer (OC). JUP was barely detectable in PF but was significantly elevated in the serum of patients with endometriosis and OC, with levels 1.33 and 2.34 times higher than controls, respectively. Additionally, JUP was found in conditioned culture media of CD14⁺/CD16⁺ monocytes aligning with our scRNA-seq data. Serum JUP levels correlated with endometriosis severity and endometrioma presence but were unaffected by dysmenorrhea, menstrual cycle, or adenomyosis. When combined with CA125 (cancer antigen 125) JUP enhanced the specificity of endometriosis diagnosis from 89.13% (CA125 measured alone) to 100%. While sensitivity remains a challenge at 19%, our results suggest that JUP’s potential to enhance diagnostic accuracy warrants additional investigation. Furthermore, employing serum JUP as a stratification marker unlocked the potential to identify additional endometriosis-related genes, offering novel insights into disease pathogenesis. Full article

Endometriosis is a chronic, estrogen-dependent inflammatory disease characterized by the presence of endometrial tissue outside the uterus, causing pelvic pain and infertility. Infertility arises mainly due to inflammatory mediators in the peritoneal fluid, contributing to local hypoestrogenism, which appears to exacerbate chronic inflammation and sensitize pelvic nerves. Local hypoestrogenism within endometriotic lesions contrasts with the systemic estrogen-dependent nature of the disease. This localized reduction in estrogen levels, resulting from an altered hormonal response, can contribute to the altered immune response and inflammation characteristic of endometriosis, potentially exacerbating tissue damage, promoting fibrosis, adhesions, and endometrioma formation that distort pelvic anatomy, and affecting fertility. Chronic pelvic pain and dyspareunia further complicate conception in affected women. In vitro fertilization (IVF) and laparoscopic surgical excision of endometriotic lesions are the two primary management options for endometriosis-related infertility, although current data provide limited guidance on when to prefer one approach over the other. It is generally accepted that treatment strategies must be individualized according to the patient’s wishes, symptomatology, age and the preferences of the woman and the couple. Timely intervention and structured follow-up for symptomatic women wishing to conceive may maximize conception rates within two years post-surgery, while minimizing the need for repeated interventions, which should be avoided. On the other hand, first-line IVF is particularly viable in cases of unoperated deep infiltrating endometriosis in asymptomatic women, or for those ineligible for or opposed to surgery. This review aims to evaluate the most recent data on endometriosis-related infertility to identify evidence-based key points that can enhance tailored management in clinical practice. Full article

Endometriosis is a chronic, inflammatory, oestrogen-dependent disorder that is defined by the presence of endometrium-like tissue in the extra-uterine environment. It is estimated to affect approximately 10% of women of reproductive age, and the cause is still largely unknown. The heterogenous nature and complex pathophysiology of the disease results in diagnostic and therapeutic challenges. This review examines the emerging role of host extracellular vesicles (EVs) in endometriosis development and progression, with a particular focus on bacterial extracellular vesicles (BEVs). EVs are nano-sized membrane-bound particles that can transport bioactive molecules such as nucleic acids, proteins, and lipids, and therefore play an essential role in intercellular communication. Due to their unique cargo composition, EVs can play a dual role, both in the disease pathogenesis and as biomarkers. Both host and bacterial EVs (HEVs and BEVs) have been implicated in endometriosis, by modulating inflammatory responses, angiogenesis, tissue remodelling, and cellular proliferation within the peritoneal microenvironment. Understanding the intricate mechanisms underlying EVs in endometriosis pathophysiology and modulation of the lesion microenvironment may lead to novel diagnostic tools and therapeutic targets. Future research should focus on uncovering the specific cargo, the inter-kingdom cell-to-cell interactions, and the anti-inflammatory and anti-microbial mechanisms of both HEVs and BEVs in endometriosis in the hope of discovering translational findings that could improve the diagnosis and treatment of the disease. Full article

Background: Deep endometriosis (DE) is a special form of endometriosis, one of the most common benign diseases in gynecology. In the specific case of DE, ectopic endometrium can be found not only in peritoneal but also in deeper tissue layers or even as parenchymal organ infiltration. Symptoms include dysmenorrhea, dyspareunia, dyschezia, and dysuria, as well as asymptomatic hydronephrosis or other organ dysfunctions. Due to a pathogenesis of the disease that has not been conclusively clarified to date, no causal therapy exists, which is why surgical resection of DE is still the gold standard for symptomatic cases. Methods: This article retrospectively describes the challenges in diagnosis and surgical treatment of DE at a German Level III Endometriosis Center, with a focus on diagnosis and surgical treatment, as well as the analysis of perioperative and postoperative complications. Results: The surgical treatment of DE is performed in most cases by minimally invasive laparoscopy (94.1%), whereas complex procedures such as ureterolysis, adhesiolysis, or preparation of the rectovaginal septum are considered standard procedures as well. The complexity of the procedures is further underlined by a high need for interdisciplinary operations (28%). Despite high complexity, severe postoperative complications occurred in only 3.1% of surgeries, with the complication rate being significantly higher whenever bowel surgery was necessary for DE resection. Conclusions: Our results emphasize the complexity and interdisciplinary nature of the disease. Therefore, treatment should preferably take place at an endometriosis center of the highest level with experienced, well-coordinated teams. Full article

This study aimed to evaluate the concentration of osteopontin in peritoneal fluid and plasma as potential biomarkers for diagnosing endometriosis. Osteopontin levels were measured using surface plasmon resonance imaging (SPRI) biosensors in patients suspected of having endometriosis. Plasma samples were collected from 120 patients, and peritoneal fluid was collected from 86 patients. Based on the detection of endometriosis lesions during laparoscopy, participants were divided into a study group (patients with endometriosis) and a control group (patients without endometriosis). The results showed no significant differences in plasma osteopontin levels between women with endometriosis and the control group (19.86 ± 6.72 ng/mL vs. 18.39 ± 4.46 ng/mL, p = 0.15). Similarly, peritoneal fluid osteopontin concentrations did not differ significantly between patients with and without endometriosis (19.04 ± 5.37 ng/mL vs. 17.87 ± 5.13 ng/mL, p = 0.29). Furthermore, osteopontin levels in both plasma and peritoneal fluid were not significantly associated with the stage of endometriosis, the presence of endometrioma, or the menstrual cycle phase. The findings of this study do not support osteopontin concentration as a reliable biomarker for endometriosis. However, further research is necessary to explore osteopontin’s potential role in the disease. Full article

Endometriosis is a common chronic disorder characterized by the growth of endometrium-like tissue outside the uterine cavity. The disease is associated with chronic inflammation and pelvic pain and may have an impact on the patient’s fertility. The causative factors and pathophysiology of the disease are still poorly recognized. The dysregulation of the immune system, aberrant tissue remodeling, and angiogenesis contribute to the disease progression. In endometriosis patients, the proteins regulating the breakdown and reorganization of the connective tissue, e.g., collagenases, and other proteases, as well as their inhibitors, show an incorrect pattern of expression. Here, we report that the expression of reversion-inducing cysteine-rich protein with Kazal motifs (RECK), one of the inhibitors of connective tissue proteases, is elevated in endometrioma cysts as compared to normal endometrium from unaffected women. We also demonstrate a reduced level of miR200b in endometriotic tissue that correlates with RECK mRNA levels. Furthermore, we employ the 12Z cell line, derived from a peritoneal endometriotic lesion, and the Ishikawa cell line, originating from endometrial adenocarcinoma to identify RECK as a direct target of miR200b. The described effect of miR200b on RECK, together with the aberrant expression of both genes in endometrioma, may help to understand the role played by the tissue remodeling system in the pathogenesis of endometriosis. Full article

Endometriosis, a debilitating condition, affects one in ten women of reproductive age. Its pathophysiology remains unclear, though deficiencies in immune surveillance are thought to create an environment conducive to the evasion of ectopic endometrial cells from the immune system. Our research explores the immunological impact of endometriosis both locally and systemically, emphasizing natural killer (NK) and T cell subpopulations. We incorporated 62 female patients who underwent laparoscopic surgery; of those, 47 had endometriosis, and 15 were controls. We collected peritoneal fluid (PF) and peripheral blood (PB) samples which were tagged with monoclonal antibodies and subsequently scrutinized using flow cytometry. Our findings revealed significant differences in immunological profiles based on demographic factors and symptomatology. In the endometriosis cohort, there was an increase in PB CD56^HiCD16^dim and PF CD8⁺ CD56^dimCD16^Hi NK cells. CD16⁺ CD4 T cell levels were significantly lower in the PB of endometriosis patients who smoke. Individuals with more severe disease displayed significantly higher levels of PB CD16⁺ CD8 T cells, which also increased in those with non-menstrual pelvic pain. Dysmenorrhea severity correlated with a progressive increase in PF CD8⁺ CD56^dimCD16^Hi NK cells. These variations in specific lymphocyte subsets, namely, within NK and T cells, suggest potential immunological mechanisms in the evolution and clinical presentation of endometriosis. Full article

Endometriosis is one of the most common causes of chronic pelvic pain and infertility that affects 10% of women of reproductive age. It is currently defined as the presence of endometrial epithelial and stromal cells at ectopic sites; however, advances in endometriosis research have some authors believing that endometriosis should be re-defined as “a fibrotic condition in which endometrial stroma and epithelium can be identified”. microRNAs (miRNAs) are regulatory molecules that potentially play a role in endometriotic lesion development. There is evidence that suggests that miRNAs, including microRNA-21 (miR-21), participate in fibrotic processes in different organs, including the heart, kidney, liver and lungs. The objective of this study was to understand the role of miR-21 and the mechanisms that can contribute to the development of fibrosis by determining how IL-6 regulates miR-21 expression and how this miRNA regulates the transforming growth factor beta (TGF-β) signaling pathway to promote fibrosis. We investigated the expression of miR-21 in the baboon and mouse model of endometriosis and its correlation with fibrosis. We demonstrated that inflammation and fibrosis are present at a very early stage of endometriosis and that the inflammatory environment in the peritoneal cavity, which includes interleukin 6 (IL-6), can regulate the expression of miR-21 in vitro and in vivo. Full article

Background: Immunological imbalances characteristic of endometriosis may develop as early as the primary manifestations of the disease in adolescence. Objective: To evaluate subpopulation dynamics of monocytes and lymphocytes in peripheral blood and peritoneal fluid of adolescents with peritoneal endometriosis at diagnosis and after 1-year progestogen therapy. Methods: This study included 70 girls, 13–17 years old, diagnosed laparoscopically with peritoneal endometriosis (n = 50, main group) or paramesonephric cysts (n = 20, comparison group). Phenotypes of monocytes and lymphocytes of the blood and macrophages of the peritoneal fluid were analyzed by flow cytometry at diagnosis and during progestogen therapy. Results: Differential blood counts of CD16⁺ (p < 0.001) and CD86⁺ (p = 0.017) monocytes were identified as independent risk factors for peritoneal endometriosis in adolescents. During the treatment, cytotoxic lymphocytes CD56dimCD16bright (p = 0.049) and CD206+ monocytes (p < 0.001) significantly increased while CD163+ monocytes decreased in number (p = 0.017). The CD56dimCD16bright blood counts before (p < 0.001) and during progestogen therapy (p = 0.006), as well as CD206⁺ blood counts during the treatment (p = 0.038), were associated with the efficacy of pain relief after 1-year progestogen therapy. Conclusions: Adolescents with peritoneal endometriosis have altered counts of pro- and anti-inflammatory monocytes and lymphocytes both before and after 1-year progestogen therapy, correlating with treatment efficacy and justifying long-term hormonal therapy. Full article

Endometriosis and adenomyosis are complex gynecological conditions characterized by diverse clinical presentations, including superficial peritoneal endometriosis (SPE), ovarian endometrioma (OMA), and deep infiltrating endometriosis (DIE). The hallmark features of these pathologies involve the manifestation of pain symptoms and infertility, and approximately 30% of patients are asymptomatic. Despite ongoing research, definitive treatments for these conditions remain elusive, and clinical management primarily revolves around medical or surgical interventions. Recent advancements in our understanding of the efficacy of various treatment modalities, including medical therapy and surgical interventions, have provided clinicians with valuable insights into pain relief and fertility preservation. This review aims to provide an updated overview of the latest literature on clinical outcomes, treatment options, and management strategies for different types of endometriosis. By synthesizing the newest available data, this review seeks to inform clinicians and guide decision making based on factors such as patients’ symptom severity, childbearing desire, and overall health. Full article

Endometriosis is an enigmatic disease, with no specific cause or trigger yet discovered. Major factors that may contribute to endometriosis in the pelvic region include environmental, epigenetic, and inflammatory factors. Most experts believe that the primary mechanism behind the formation of endometrial lesions is associated with Sampson’s theory of “retrograde menstruation”. This theory suggests that endometrial cells flow backward into the peritoneal cavity, leading to the development of endometrial lesions. Since this specific mechanism is also observed in healthy women, additional factors may be associated with the formation of endometrial lesions. Current treatment options primarily consist of medical or surgical therapies. To date, none of the available medical therapies have proven effective in curing the disorder, and symptoms tend to recur once medications are discontinued. Therefore, there is a need to explore and develop novel biomedical targets aimed at the cellular and molecular mechanisms responsible for endometriosis growth. This article discusses a recent molecular pathophysiology associated with the formation and progression of endometriosis. Furthermore, the article summarizes the most current medications and surgical strategies currently under investigation for the treatment of endometriosis. Full article