Search Results (157)

Background: Endometriosis is a chronic inflammatory condition affecting 10–15% of women of reproductive age. Genome-wide association studies (GWASs) have accounted for only a fraction of its high heritability, indicating the need for alternative approaches to identify rare genetic variants contributing to its etiology. To this end, we performed whole-exome sequencing (WES) in a multi-affected family. Methods: A multigenerational family was studied, comprising three sisters, their mother, grandmother, and a daughter, all diagnosed with endometriosis. WES was conducted on the three sisters and their mother. We used the enGenome-Evai and Varelect software to perform our analysis, which mainly focused on rare, missense, frameshift, and stop variants. Results: Bioinformatic analysis identified 36 co-segregating rare variants. Six missense variants in genes associated with cancer growth were prioritized. The top candidates were c.3319G>A (p.Gly1107Arg) in the LAMB4 gene and c.1414G>A (p.Gly472Arg) in the EGFL6 gene. Variants in NAV3, ADAMTS18, SLIT1, and MLH1 may also contribute to disease onset through a synergistic and additive model. Conclusions: We identified novel candidate genes for endometriosis in a multigenerational affected family, supporting a polygenic model of the disease. Our study is an exploratory family-based WES study, and replication and functional studies are warranted to confirm these preliminary findings. Full article

Endometriosis is a disease characterized by the presence of endometrial glands and stroma outside of the uterine corpus, often clinically presenting with pain and/or infertility. Ectopic lesions exhibit features characteristic of epithelial-to-mesenchymal transition (EMT), a process in which epithelial cells lose polarity and acquire mesenchymal traits, including migratory and invasive capabilities. During the process of EMT, epithelial traits are downregulated, while mesenchymal traits are acquired, with cells developing migratory ability, increasing proliferation, and resistance to apoptosis. EMT is promoted by exposure to hypoxia and stimulation by transforming growth factor-β (TGF-β), platelet-derived growth factor (PDGF), and estradiol. Signaling pathways that promote EMT are activated in most ectopic lesions and involve transcription factors such as Snail, Slug, ZEB-1/2, and TWIST-1/2. EMT-specific molecules present in the serum of women with endometriosis appear to have diagnostic potential. Strategies targeting EMT in animal models of endometriosis have demonstrated regression of ectopic lesions, opening the door for novel therapeutic approaches. This review summarizes the current understanding of the role of EMT in endometriosis and highlights potential targets for EMT-related diagnosis and therapeutic interventions. Full article

Lipedema is a chronic, estrogen-sensitive adipose tissue disorder characterized by disproportionate subcutaneous fat accumulation, fibrosis, inflammation, and resistance to fat mobilization. Despite its high prevalence, lipedema remains poorly understood and frequently misdiagnosed. This narrative review proposes a novel pathophysiological model in which menopause acts as a critical turning point in the progression of lipedema, driven by estrogen receptor imbalance (ERβ predominance over ERα), intracrine estrogen excess, and adipose tissue dysfunction. We demonstrate how menopause amplifies adipose tissue dysfunction by suppressing ERα signaling; enhancing ERβ activity; and disrupting mitochondrial function, insulin sensitivity, and lipid oxidation. Concurrently, the upregulation of aromatase and 17β-HSD1, combined with the suppression of 17β-HSD2, sustains localized estradiol excess, perpetuating inflammation, fibrosis, and immune dysregulation. The molecular signature observed in lipedema closely mirrors that of other estrogen-driven gynecological disorders, such as endometriosis, adenomyosis, and uterine fibroids. Understanding these molecular mechanisms highlights the pivotal role of menopause as a catalyst for disease progression and provides a rationale for targeted therapeutic strategies, including hormonal modulation and metabolic interventions. This review reframes lipedema as an estrogen receptor-driven gynecological disorder, offering a new perspective to improve clinical recognition, diagnosis, and management of this neglected condition. 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, estrogen-dependent inflammatory condition that affects multiple organ systems and significantly impairs the quality of life in women of reproductive age. While conventional hormonal therapies may alleviate symptoms of endometriosis, they are also frequently associated with intolerable side effects. As a result, there is growing interest in complementary, non-invasive strategies to support long-term disease management. This review explores the potential of plant-based diets and personalized nutrition as adjunctive approaches in endometriosis care. Plant-based dietary patterns, which are rich in antioxidants, phytochemicals, dietary fiber, and essential micronutrients, have been shown to reduce systemic inflammation, modulate estrogen activity, and alleviate pelvic pain. Additionally, the use of medicinal plants, such as curcumin and ginger, has demonstrated anti-inflammatory and anti-proliferative effects in preclinical studies. Moreover, identifying and addressing individual food sensitivities, particularly to gluten, dairy, or fermentable oligosaccharides, disaccharides, monosaccharides, and polyols, may improve gastrointestinal and inflammatory symptoms in susceptible individuals. Future research should focus on high-quality clinical trials and integrative care models to evaluate the long-term efficacy, safety, and sustainability of these individualized nutritional interventions in the holistic management of endometriosis. Full article

Background/Objectives: Endometrial cancer (EC) is the sixth most common cancer among women worldwide, and its global incidence has significantly increased over the past three decades. Despite its substantial burden, comprehensive reviews of EC-related research remain limited. This study employs topic modeling to analyze and classify recent research trends in EC. Methods: We identified studies related to endometrial carcinoma published between 2019 and 2023 in PubMed, Web of Science, and the Cochrane Library. The search was conducted using the following terms: endometr* AND (neoplasm* OR cancer* OR carcinoma*) NOT endometriosis. Word clouds were constructed and topic modeling was performed to analyze research activity. Results: A total of 2188 studies were selected, and 11,552 terms were extracted. High-frequency and TF-IDF-weighted keywords included ‘cancer’, ‘risk’, ‘survival’, ‘stage’, ‘tumor’, ‘surgery’, and ‘OS.’ Topic modeling analysis identified ten clusters, categorized as follows: ‘Gynecologic cancer’, ‘Surgical staging’, ‘Therapeutic efficacy’, ‘Diagnosis’, ‘Surgical management’, ‘Multimodal treatment’, ‘Molecular treatment’, ‘Risk factors’, ‘Survival’, and ‘Hormonal regulation.’ Conclusions: This study highlights that recent research on EC has primarily focused on surgical decision making, outcome prediction, and patient survival. Future studies should place greater emphasis on multimodal treatment and prevention—particularly through the identification of risk factors—as well as on improving patients’ quality of life. Full article

Endometriosis is a chronic, hormone-dependent disease that affects women of reproductive age. It leads to numerous adverse clinical symptoms, which significantly impact women’s quality of life. The chronic nature of the disease and its recurrence are the main reasons for the search for new, non-hormonal drugs and drug candidates, either as adjunct treatment options or alternative therapies. The catechin found in green tea, epigallocatechin gallate (EGCG), has been shown to exhibit a wide array of biological activities, which may also contribute to its potential effectiveness in treating endometriosis. The poor physicochemical stability and relatively low bioavailability of EGCG have stimulated the development of a peracetylated prodrug (pro-EGCG) and other solutions, based on nanotechnology, that would eliminate the problems with EGCG. In this review article, we summarize the studies on the effects of EGCG, pro-EGCG, and EGCG-based nanoparticles on the course of endometriosis published in the GoogleScholar and PubMed databases. Of note is the fact that the results of in vitro and animal model studies have suggested that EGCG and pro-EGCG can reduce the number of endometriosis foci and their size and volume, and they can prevent fibrosis by affecting multiple molecular factors and signaling pathways. The promising results provide a basis for using green herbal extracts for endometriosis treatment in a clinical trial. Nevertheless, it should be emphasized that the number of studies on the topic is currently very limited; further expansion in the coming years is necessary. Broad, well-designed clinical trials are also essential to validate the true potential of EGCG and related compounds in the fight against endometriosis. Full article

Cellular senescence leads to stable cell cycle arrest and an inflammatory senescence-associated secretory phenotype that varies with stressor and cell type. To mitigate these effects and improve health, senotherapeutics (e.g., senolytics and senomorphics) have been developed. Senescent-like endometrial stromal cells (eSCs) lining the uterus of patients with endometriosis and infertility are proposed to impair decidualization, a differentiation process required for uterine receptivity in humans. Quercetin, a natural flavonoid senolytic, dramatically improves decidualization and reduces endometriosis in rodent models. However, little is known about the comparative effects of various senotherapeutics on eSCs. Using menstrual effluent-derived eSCs, we evaluated the effects of flavonoid and non-flavonoid compounds on eSC functions associated with endometriosis, aiming to identify optimal senotherapeutics for future clinical trials. Among flavonoids tested, all senolytics (quercetin, fisetin, and luteolin) and kaempferol, a senomorphic, significantly improved decidualization without cytotoxicity. Although non-flavonoids exhibited notable cytotoxicity, dasatinib, but neither ABT-737 nor navitoclax, enhanced decidualization. Flavonoid senotherapeutics and dasatinib significantly inhibited eSC migration. Mechanistic studies revealed that all flavonoids and dasatinib suppressed AKT phosphorylation and upregulated p53 expression. Notably, only quercetin and fisetin reduced ERK1/2 phosphorylation. Furthermore, flavonoid-senolytics and dasatinib consistently eliminated senescent eSCs. These findings support future studies to assess the therapeutic potential of in vivo supplementation with flavonoid senolytics on eSC function using menstrual effluent. Full article

Background/Objectives: Endometriosis, a chronic and debilitating gynecological disorder, exacts a heavy clinical and socioeconomic toll on women’s lives. Despite its prevalence, its timely diagnosis and effective management are hindered by pervasive knowledge gaps among frontline nursing professionals, and these are especially pronounced in under-researched regions such as Al-Jouf, Saudi Arabia. Aim: Guided by the Knowledge–Attitude–Practice model, this study aimed to assess the level of endometriosis-related knowledge among nurses in the Al-Jouf region of Saudi Arabia and to identify the sociodemographic and professional determinants of knowledge levels. Methods: A cross-sectional, descriptive-analytical design was employed between January and July 2024, enrolling 215 nurses from a principal maternity and children’s hospital and two primary healthcare centers in Sakaka. A rigorously validated, bilingual 20-item questionnaire assessing four domains (definition, risk factors, clinical manifestations, and treatment goals) was administered. Data were analyzed using descriptive statistics, multiple linear regression, and binary logistic regression to elucidate predictors of knowledge. Results: A concerning picture emerged: 61% of participants scored below 60% (indicative of low knowledge), with only 6% achieving high scores. Higher educational attainment proved the strongest predictor (β = 0.415, p < 0.001), followed by age (β = 0.232, p < 0.001), years of experience (β = 0.149, p = 0.041), and direct patient care exposure (β = 0.168, p = 0.021). Collectively, these factors explained 37.6% of the variance in knowledge scores, underscoring a critical deficit in endometriosis management preparedness. Conclusions: The stark deficiencies in endometriosis knowledge among nurses in Al-Jouf call for immediate, tailored educational and policy interventions. Strengthening clinical competencies is essential for fostering early diagnosis and improving care outcomes for women burdened by this complex condition. Full article

Endometriosis is a gynecological disease characterized by the presence of endometrium-like cells located outside the uterus. The most widely accepted theory for endometriosis development, retrograde menstruation, does not account for extra-pelvic lesions or ones found on other organs in the peritoneal cavity. Similar to ovarian cancer, endometriosis cells can interact with the mesothelial cells of the peritoneal cavity. In ovarian cancer metastasis, ovarian cancer cell spheroids attach and push away the mesothelial cells lining the peritoneal cavity, clearing the mesothelial layer. Since endometriosis cells are known to interact with the mesothelium, we hypothesized that endometriosis cells would be able to form spheroids capable of undergoing mesothelial clearance. To test this, we designed an in vitro mesothelial clearance assay using endometriosis spheroids and a mesothelial cell monolayer. Our results demonstrate that normal and endometriotic epithelial cell spheroids can perform mesothelial clearance similar to ovarian cancer spheroids, though normal endometrial cells do not clear as well as endometriosis cells. Additionally, we demonstrated that our mesothelial clearance assay can test potential pharmacological therapies for endometriosis prior to clinical trials. These results give insight into the development of endometriosis lesions, but further research is needed to determine the mechanisms behind mesothelial clearance in endometriosis. Full article

Background: Laparoscopic surgery for endometriosis presents unique challenges due to the complexity of and variability in lesion appearances within the abdominal cavity. This study investigates the application of deep learning models for object detection in laparoscopic videos, aiming to assist surgeons in accurately identifying and localizing endometriosis lesions and related anatomical structures. A custom dataset was curated, comprising of 199 video sequences and 205,725 frames. Of these, 17,560 frames were meticulously annotated by medical professionals. The dataset includes object detection annotations for 10 object classes relevant to endometriosis, alongside segmentation masks for some classes. Methods: To address the object detection task, we evaluated the performance of two deep learning models—FasterRCNN and YOLOv9—under both stratified and non-stratified training scenarios. Results: The experimental results demonstrated that stratified training significantly reduced the risk of data leakage and improved model generalization. The best-performing FasterRCNN object detection model achieved a high average test precision of 0.9811 ± 0.0084, recall of 0.7083 ± 0.0807, and mAP50 (mean average precision at 50% overlap) of 0.8185 ± 0.0562 across all presented classes. Despite these successes, the study also highlights the challenges posed by the weak annotations and class imbalances in the dataset, which impacted overall model performances. Conclusions: In conclusion, this study provides valuable insights into the application of deep learning for enhancing laparoscopic surgical precision in endometriosis treatment. The findings underscore the importance of robust dataset curation and advanced training strategies in developing reliable AI-assisted tools for surgical interventions. The latter could potentially improve the guidance of surgical interventions and prevent blind spots occurring in difficult to reach abdominal regions. Future work will focus on refining the dataset and exploring more sophisticated model architectures to further improve detection accuracy. Full article

Background and Objectives: Dysbiosis of the oral–gut axis is related to several extraintestinal inflammatory diseases, including endometriosis. This study aims to assess the microbial landscape and pathogenic potential of distinct biological niches during endometriosis. Materials and Methods: A microbiome meta-analysis was conducted on 182 metagenomic sequences (79 of fecal and 103 of vaginal origin) from women with and without endometriosis. Fecal and vaginal microbial diversity, differential abundance, and functional analysis based on disease status were assessed. Random forest, gradient boosting, and generalized linear modeling were used to predict endometriosis based on differentially enriched bacteria. Results: Only intestinal microbes displayed distinctive taxonomic and functional characteristics in women with endometriosis compared to control women. Taxonomic differences were quantified using the microbial endometriosis index (MEI), which effectively distinguished between individuals with and without the disease. The observed functional enrichment pointed to proinflammatory pathways previously related to endometriosis development. Conclusions: Dysbiosis in the oral–gut microbial community appears to play a prevalent role in endometriosis. Our findings pave the ground for future studies exploring the potential mechanistic involvement of the oral–gut axis in disease pathogenesis. Full article

Fertility is a dynamic, multifactorial process governed by hormonal, immune, metabolic, and environmental factors. Recent evidence highlights the gut microbiota as a key systemic regulator of reproductive health, with notable impacts on endometrial function, implantation, pregnancy maintenance, and the timing of birth. This review examines the gut–endometrial axis, focusing on how gut microbial communities influence reproductive biology through molecular signaling pathways. We discuss the modulatory roles of microbial-derived metabolites—including short-chain fatty acids, bile acids, and tryptophan catabolites—in shaping immune tolerance, estrogen metabolism, and epithelial integrity at the uterine interface. Emphasis is placed on shared mechanisms such as β-glucuronidase-mediated estrogen recycling, Toll-like receptor (TLR)-driven inflammation, Th17/Treg cell imbalance, and microbial translocation, which collectively implicate dysbiosis in the etiology of gynecological disorders including endometriosis, polycystic ovary syndrome (PCOS), recurrent implantation failure (RIF), preeclampsia (PE), and preterm birth (PTB). Although most current evidence remains correlational, emerging insights from metagenomic and metabolomic profiling, along with microbiota-depletion models and Mendelian randomization studies, underscore the biological significance of gut-reproductive crosstalk. By integrating concepts from microbiology, immunology, and reproductive molecular biology, this review offers a systems-level perspective on host–microbiota interactions in female fertility. Full article

Background: Endometriosis is a benign gynecologic condition that has the risk of malignant transformation in approximately 0.5–1% of cases, most of which develop into endometriosis-associated ovarian cancers (EAOCs), such as clear cell and endometrioid adenocarcinomas. The current systematic review aims to condense recent information on the genetic and molecular mechanisms, clinical risk factors, and possible therapeutic targets of the malignant transformation of endometriosis. Methods: A systematic literature search of PubMed, Europe PMC, and Google Scholar was carried out according to PRISMA guidelines for articles published until December 2024. Following a screening of 44,629 titles, 43 full articles were included after meeting inclusion criteria. No case reports or reviews were included, and articles had to mention a malignant transformation of endometriosis and not just a diagnosis of cancer. The quality and risk of bias of studies were evaluated using ROBINS-I. Results: Malignant transformation of endometriosis is associated with genetic alterations, including ARID1A mutations, microsatellite instability, and abnormal PI3K/Akt and mTOR pathway activation. Increased oxidative stress, inflammation-driven mismatch repair deficiency, and epigenetic alterations like RUNX3 and RASSF2 hypermethylation are implicated in carcinogenesis. Clinical risk factors are advanced age (40–60 years), large ovarian endometriomas (>9 cm), postmenopausal status, and prolonged estrogen exposure. Imaging techniques like MR relaxometry and risk models based on machine learning are highly predictive for early detection. Conclusions: Endometriosis carcinogenesis is a multifactorial process driven by genetic changes, oxidative stress, and inflammatory mechanisms. Identification of high-risk individuals through molecular and imaging biomarkers may result in early detection and personalized therapy. Further research should aim at the development of more precise predictive models and exploration of precision medicine approaches to inhibit the emergence of EAOC. Full article

Endometriosis is a chronic gynaecological disease characterised by endometrial-like tissue found external to the uterus. While several studies have reported strong evidence of a genetic contribution to the disease, studies on the environmental impact on endometriosis are limited. DNA methylation (DNAm) can be influenced by genetic and environmental factors and serves as a useful biological marker of the effects of genetic and environmental exposures on complex diseases. This study aims to develop a methylation risk score (MRS) for endometriosis to increase the power to detect DNAm signals associated with the disease and enhance our understanding of the pathogenesis of the disease. Endometrial methylation and genotype data from 318 controls and 590 cases were analysed. MRSs were developed using several different models. MRS performances were evaluated by splitting samples into training and test sets based on independent cohort institutions, and the area under the receiver-operator curve (AUC) was calculated. The maximum AUC obtained from the best-performing MRS is 0.6748, derived from 746 DNAm sites. The classification performance of MRS and polygenic risk score (PRS) combined was consistently higher than PRS alone. This study demonstrates that there are DNAm signals independent of common genetic variants associated with endometriosis. Full article