What's new in endo & adenomyosis research

Ovarian endometrioma (OMA), an endometriosis subtype, involves hemorrhagic cysts formed by ectopic endometrial-like tissue, causing pelvic pain, inflammation, and infertility by disrupting ovarian function. Despite its impact, the single-cell dynamics in OMA follicular fluid are poorly understood. We performed scRNA-seq (10x Genomics) on follicular fluid from a patient's affected (2793 cells) and unaffected (4699 cells; control) ovaries. Analysis revealed four cell types, including a novel TCR+ macrophage subtype. Affected-side granulosa cells showed abnormal developmental trajectories linked to dysregulated steroid pathways. Immune cells exhibited heightened inflammation and reduced macrophage phagocytosis. Cell-cell communication highlighted prominent MIF and MK signaling from granulosa cells. This study provides the first single-cell transcriptomic profile of OMA follicular fluid, elucidating aberrant granulosa cell development, immune dysregulation, and distinctive cellular interactions, enhancing understanding of OMA's impact on follicular development and suggesting potential diagnostic/therapeutic targets.

Integrative WES–RNA‑seq profiling highlights a coordinated invasion‑like program in endometriosis with functional dependence on PI3K/AKT signaling, supporting PI3K/AKT as a mechanistically grounded target for anti‑invasive strategies in endometriosis.

(No abstract on file for this paper.)

IMPORTANCE: Endometriosis, a chronic inflammatory condition affecting 10% of reproductive-aged individuals, remains underdiagnosed and poorly managed due to a limited understanding of its pathogenesis. Emerging evidence highlights the gut and reproductive tract microbiota as key modulators of estrogen metabolism, immune dysregulation, and inflammation, offering novel insights into disease mechanisms and therapeutic opportunities. OBJECTIVE: To synthesize current evidence on the mechanistic roles of microbiota in endometriosis pathogenesis, evaluate the diagnostic and therapeutic potential of microbial biomarkers and microbiota-targeted interventions, and identify priorities for translational research. EVIDENCE ACQUISITION: A systematic review of PubMed, Scopus, and Web of Science databases identified preclinical and clinical studies exploring microbiota-endometriosis interactions. The search strategy incorporated the terms "endometriosis" in combination with "microbiota," "reproductive tract," and "gut" to investigate microbial associations within gastrointestinal and reproductive systems in the context of the disease. RESULTS: Dysbiotic microbial profiles, characterized by reduced Lactobacillus and elevated Fannyhessea species, correlate with altered estrogen metabolism, pro-inflammatory cytokine production (eg, IL-6, TNF-α), and impaired immune surveillance in endometriosis. Preclinical studies demonstrate that probiotics and FMT attenuate lesion growth and inflammation in animal models, though human data remain limited. Noninvasive microbial signatures show promise for diagnostic applications, while causal validation in germ-free models and personalized microbiota-based therapies represent critical research gaps. CONCLUSIONS: The microbiota modulates endometriosis progression through hormonal, immune, and inflammatory pathways. Microbial biomarkers and therapies may improve diagnosis and treatment but require rigorous clinical validation. RELEVANCE: Advancing microbiota research could enable noninvasive diagnostics, precision therapies, and prevention strategies.

Catamenial pneumothorax is an uncommon manifestation of thoracic endometriosis syndrome, usually associated with small right-sided diaphragmatic fenestration. We report an extreme presentation in a woman in her late 40s who developed acute right-sided chest pain one day prior to menstruation. Initial imaging revealed a right pneumothorax, which resolved after intercostal drainage. However, subsequent computed tomography revealed a massive defect in the right hemidiaphragm with herniation of the entire right hepatic lobe, gallbladder, and upper pole of the right kidney into the thoracic cavity. A multidisciplinary surgical strategy was adopted, involving abdominal reduction of the herniated viscera, followed by video-assisted thoracoscopic mesh repair of the diaphragm and talc pleurodesis. Postoperative hormonal suppression was initiated. The patient remained asymptomatic without recurrence at 18 months. This case highlights that catamenial pneumothorax may represent advanced chronic diaphragmatic pathology, even at the first clinical presentation.

Progesterone resistance in endometriosis reduces the efficacy of progestin. The non-classical progesterone receptor, progesterone receptor membrane component 1 (PGRMC1) may regulate progesterone signaling in the normal endometrium, but its expression and role in endometriosis remain unknown. We aimed to investigate PGRMC1 expression in endometriosis and its role in progesterone resistance. PGRMC1 expression in normal endometrium (NE), eutopic endometrium in patients with endometriosis (EE), and ovarian endometrioma (OE) was examined using immunohistochemistry. Cultured OE stromal cells (SCs) were subjected to PGRMC1 knockdown using siRNA and treated with AG205 (a PGRMC1 inhibitor) and RU486 (a PR inhibitor) under progesterone stimulation. Progesterone responsiveness was assessed by measuring IGFBP1 and PRL expression through real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). PGRMC1 expression in NESCs and EESCs was significantly lower in the secretory phase than in the proliferative phase (P < 0.01), with no similar changes observed in OE. Following siRNA-mediated PGRMC1 knockdown in OESCs, IGFBP1 and PRL expression was significantly upregulated (P < 0.05). Notably, treatment with siRNA and progestin induced significantly higher IGFBP1 and PRL expression than treatment with progestin alone (P < 0.05). AG205 induced similar effects on IGFBP1and PRL expression (P < 0.05), suggesting that suppression of PGRMC1 expression enhances progestin responsiveness in OESCs. However, AG205-induced IGFBP1 expression was abolished following treatment with RU486, suggesting that PGRMC1 acts through PR. In conclusion, suppressing PGRMC1, which is consistently expressed throughout the menstrual cycle in endometriotic lesions, may restore progesterone sensitivity and improve the efficacy of progestin-based therapies for endometriosis.

Endometriosis is a chronic gynecological disorder affecting up to 10% of women of reproductive age and is characterized by the presence of endometrial-like tissue outside the uterus. The condition is associated with chronic pelvic pain, dysmenorrhea, dyspareunia, and infertility, and remains difficult to diagnose at early stages. Recent evidence suggests that endometriosis shares genetic and molecular pathways with other chronic pain and inflammatory disorders. Identifying reliable biomarkers is therefore essential to improve risk stratification and support earlier evaluation. Multiple domains have emerged as candidate markers for risk stratification, including genetic and epigenetic alterations, dysmenorrhea, migraine, autoimmune and endocrine disorders, and stress and early-life adversity. These factors have been associated with disease initiation, lesion development, and symptom severity. Understanding their interactions could support multimodal risk stratification approaches and guide preventive strategies. This narrative review highlights the multifactorial nature of endometriosis and synthesizes current evidence on emerging predictive markers. Although progress has been made, large prospective studies are still needed to validate these markers and facilitate the development of targeted interventions.

The research by Chen et al. (2024) presents an innovative hypothesis linking creatine metabolism to ferroptosis resistance in endometriotic stromal cells via PrP suppression. While conceptually valuable, methodological aspects warrant reflection. A primary concern involves the supraphysiological creatine concentrations used, whose translational relevance is questionable without pharmacokinetic data confirming these levels in the peritoneal environment, particularly in light of available clinical metabolomics data suggesting differences in creatine levels in peritoneal fluid under physiological and pathological conditions. Furthermore, the proposed direct suppression of PrP ferrireductase activity would benefit from complementary biochemical validation using purified systems and affinity measurements to consolidate the molecular mechanism. Although human samples were included, the small cohort size and lack of control for confounding variables limit the specificity of interpretation, source attribution, and the external generalizability of the findings. Finally, future studies should target endogenous creatine synthesis or transport to clarify whether creatine is a causal driver of ferroptosis resistance or simply associated with the inflammatory microenvironment. Overall, Chen et al. provide an exciting contribution; these constructive considerations aim to support future refinements that will solidify the proposed model and its clinical significance.

The identification of the appendix often presents a diagnostic challenge due to its significant anatomical variability, compounded by the frequency with which appendiceal pathologies manifest as atypical clinical presentations that mimic diverse abdominal and pelvic conditions. Beyond acute appendicitis, a wide spectrum of inflammatory, infiltrative, and neoplastic processes can involve the appendix, necessitating the rigorous recognition of their distinct imaging signatures. This pictorial essay reviews the normal anatomy of the appendix, its positional variations, and the spectrum of diseases that may affect it, including acute appendicitis, endometriosis, epiploic appendagitis, appendiceal diverticulitis, mucocele, and primary tumors. While computed tomography (CT) remains the gold standard for primary diagnostic evaluation, magnetic resonance imaging (MRI) serves as a critical complementary modality in specific clinical scenarios, providing superior soft-tissue characterization and improving diagnostic confidence in challenging cases. Recognition of anatomical variants and the primary mimics of the appendix is essential for the accurate interpretation of abdominal imaging studies.

Subepithelial lesions (SELs) in the lower gastrointestinal tract are rare, and diagnosis and treatment of colorectal SELs are often challenging. Although endoscopic ultrasound-guided tissue acquisition (EUS-TA) is useful for minimally invasive histological diagnosis, few reports have described its use for right-sided colonic SELs because advancing an oblique-viewing echoendoscope into the right colon is difficult. A 30-year-old woman was referred to our hospital after colonoscopy revealed a protruding cecal lesion suggestive of an SEL. Contrast-enhanced computed tomography showed a 37-mm contrast-enhancing mass and an adjacent lesion, thought to be an enlarged lymph node, and gastrointestinal stromal tumor was suspected. A forward-viewing echoendoscope was inserted transanally and advanced successfully to the cecum in 4 min. EUS-TA of the cecal mass was performed using a 19-gauge fine-needle biopsy needle, and EUS-TA of the adjacent lesion was performed using a 25-gauge fine-needle biopsy needle. Histopathological and immunohistochemical examinations showed endometrial glands and stroma with positivity for estrogen receptor, progesterone receptor, and CD10, leading to a definitive diagnosis of endometriosis. This diagnosis enabled initial non-surgical management without immediate surgery.

BACKGROUND: Postoperative pain following laparoscopic surgery can delay recovery and increase opioid use. Lower insufflation pressures have been consistently shown to reduce pain in general surgery procedures, but their impact in gynecologic surgery is not well established. OBJECTIVE: (s): To investigate the effect of varying insufflation pressures on postoperative pain and operative field visualization among patients undergoing laparoscopic gynecologic surgery. STUDY DESIGN: We conducted a randomized controlled trial of patients undergoing conventional laparoscopy within a minimally invasive gynecologic surgery practice at an academic hospital in the United States. Exclusion criteria included pregnancy, urgent surgery, concomitant non-gynecologic surgery, allergy/intolerance to standard perioperative pain medications, and planned postoperative admission. Patients were randomized to pressures of 10 mmHg, 12 mmHg, or 15 mmHg. The assigned pressure was set following laparoscopic entry and could be changed at the surgeon's discretion. The primary outcome was the maximum post-anesthesia care unit (PACU) pain score (11-point numerical rating scale). Secondary outcomes included surgeon satisfaction with operative field visualization, alterations in insufflation pressure, operative time, estimated blood loss, first and last documented PACU pain scores, PACU length of stay, and postoperative opioid requirements. RESULTS: From May 2024 to February 2025, 147 patients were randomized and included in the analysis (49 per group). Procedures performed among the cohort included adnexal surgery (cystectomy, salpingectomy, or oophorectomy) (64.6%), excision of endometriosis (61.2%), myomectomy (34.0%), ureterolysis (29.9%), lysis of adhesions (25.9%), hysterectomy (25.1%), and appendectomy (9.5%). There was no difference in maximum PACU pain scores among groups (median 6.0 [IQR 3.0-7.0] at 10 mmHg, 6.0 [3.0-7.0] at 12 mmHg, and 6.0 [4.0-7.0] at 15 mmHg; P = 0.59). Surgeons reported adequate visualization in 83.3% of cases at 10 mmHg, 97.9% at 12 mmHg, and 100% at 15 mmHg (P < 0.001). Insufflation pressure was increased in 6 cases due to suboptimal visualization, all in the 10 mmHg group, and decreased in 3 cases due to concern for abdominal wall overdistension. No differences were observed in opioid use or other secondary outcomes. CONCLUSIONS: Lower insufflation pressures did not reduce postoperative pain or opioid requirements in this randomized cohort of patients undergoing laparoscopic gynecologic surgery. Operative field visualization was rarely compromised at 10 mmHg and was unaffected at 12 mmHg. Intraoperative pressure changes were uncommon and occurred in both directions, supporting individualization of insufflation pressure based on patient factors. The findings of this study may be most applicable to similar patient populations undergoing complex benign gynecologic procedures, particularly excision of endometriosis.

(No abstract on file for this paper.)

PURPOSE: To evaluate intraobserver and interobserver agreement in the interpretation of subtle MRI findings classified as minimal endometriosis, to assess the impact of the Kappa paradox in low-prevalence compartments, and to compare blinded rereads with the original prospective reports. MATERIALS AND METHODS: In this retrospective study, 100 pelvic MRI examinations (50 originally reported as minimal or incipient endometriosis and 50 originally reported as normal) were independently reviewed by three radiologists on two blinded occasions 4-8 weeks apart. Seven anatomical compartments were assessed. Agreement was measured with Cohen's Kappa, Fleiss' Kappa, PABAK, Gwet's AC1, and positive/negative agreement. Original reports were used as a clinical reference for descriptive comparison, and exact McNemar tests assessed directional asymmetry of discordance. RESULTS: Intraobserver agreement for any finding was fair (mean Kappa = 0.36, 95%CI 0.16-0.54; AC1 = 0.49), and interobserver agreement was also fair (Fleiss Kappa = 0.28; AC1 = 0.40). Agreement was consistently stronger for negative than for positive classifications. Ovarian findings showed the highest reproducibility, whereas very low-prevalence compartments showed a marked Kappa paradox. Multicategory analysis of uterosacral ligament laterality reduced agreement, mainly because unilateral-versus-bilateral disagreement remained frequent among positive cases. Comparison with original reports showed slight-to-moderate agreement (Kappa 0.18-0.46), with specificity (76-86%) consistently exceeding sensitivity (32-66%), indicating a more restricted threshold on blinded rereads, particularly for uterosacral ligament involvement. CONCLUSIONS: Agreement for subtle MRI findings interpreted as minimal endometriosis was only fair and clearly lower than that usually reported for deep endometriosis. Low-prevalence compartments were strongly affected by the Kappa paradox, and the low-to-moderate discordance with original reports, driven primarily by lower sensitivity on blinded rereads, supports the need for clearer operational criteria and more standardized interpretation.

Background Ovarian endometriosis is a common yet frequently misdiagnosed gynecological condition. The accuracy of health information on video platforms like YouTube, Douyin, and Bilibili remains uncertain.Methods On June 15, 2025, we searched YouTube(English, international), Douyin(Mandarin, China domestic), and Bilibili(Mandarin, China domestic) for the terms ‘chocolate cyst’ and ‘ovarian endometriosis’, retrieving the top 100 videos from each platform. After exclusions, 209 videos were analyzed. Videos were categorized by uploader type and content topic. Quality and reliability were assessed using three standardized instruments: the Global Quality Score (GQS), the Video Information and Quality Index (VIQI), and the modified DISCERN (mDISCERN) tool. Statistical analyses included the Kruskal-Wallis test and correlation analyses to evaluate and compare videos across platforms.Results Douyin videos were shortest but received the highest engagement, whereas YouTube(English, predominantly India-sourced) provided the most comprehensive and reliable content (median GQS 3.0 vs. 2.0–2.5; p < 0.001). Professional uploaders produced significantly higher-quality and more reliable content than non-professionals (p 65%), while staging, prognosis, and fertility indices were largely absent. Video duration correlated positively with quality metrics, whereas popularity indicators (e.g. likes) were inversely associated with quality.Conclusions Short-video platforms provide accessible information on ovarian endometriosis but overall reliability remains limited. YouTube outperformed Douyin and Bilibili in quality and reliability, yet critical prognostic content is missing. To enhance public health education, platforms should prioritize verified professional content and develop dedicated health modules, while clinicians should actively contribute accurate, engaging resources.

Background: Endometriosis is a chronic, estrogen-dependent inflammatory disorder associated with pain and immune dysregulation. Omega-3 (n-3) fatty acids and fish-derived bioactive lipids may modulate inflammation and metabolism. This study investigated whether adding fish-derived lipids (FDLs) to a Healthy Eating Plate diet improves inflammatory markers, gut inflammation, pain, and quality of life in women with endometriosis. Methods: In this 12-week randomized controlled trial, 46 women with confirmed endometriosis were assigned to either a Healthy Eating Plate diet alone (control group, CG) or the same diet plus FDLs (intervention group, IG). Primary outcomes included serum cytokine concentrations (interleukin [IL]-1β, IL-6, IL-8, IL-10, and tumor necrosis factor-alpha [TNF-α]) and fecal calprotectin (CAL). Secondary outcomes included pain intensity measured using the visual analog scale (VAS) and health-related quality of life assessed with the Endometriosis Health Profile-30 (EHP-30). Results: IL-10 levels (pg/mL) increased in the IG (32.5 ± 51.5 to 265 ± 508; p = 0.024) with a significant adjusted effect (ANCOVA: 5.07 [95% CI: 1.32–19.48], p = 0.019). Other cytokines showed heterogeneous responses, and CAL levels remained unchanged. EHP-30 Pain scores improved within both groups (CG p = 0.016; IG p = 0.002) without significant between-group change or adjusted effects (all p > 0.05). VAS scores decreased within the IG (5.0 ± 2.1 to 4.3 ± 2.1; p = 0.011), although there were no between-group differences in change and ANCOVA (all p > 0.05). However, ≥1-point responder rates were higher in the IG vs. CG (73.9% vs. 34.8%): adjusted RR = 2.11 (95% CI: 1.16; 3.89; p = 0.014). Conclusions: Overall, FDL supplementation was associated with a selected regulatory immune signal, reflected mainly by the IL-10 response, while most inflammatory, pain-related, and quality-of-life outcomes did not show consistent significant between-group effects. The observed greater likelihood of pain reduction in the FDL-supplemented group of women with endometriosis, along with the IL-10 response, should be interpreted with caution and confirmed in larger studies with longer follow-up/intervention time, taking into account the potential mechanisms of biological response.

(No abstract on file for this paper.)

The human microbiome, a dynamic endocrine organ, exerts profound systemic influence through the production of bioactive metabolites. While the microbiome-gut-brain axis is well-established, the direct conduit between the gut microbiota and the reproductive system, the Microbiome-Gut-Gonad Axis, remains an emerging paradigm. This review explored cutting-edge evidence to construct a comprehensive model of the Microbiome-Gut-Gonad axis, focusing on the mechanistic roles of specific microbial metabolites in both physiological reproductive function and the pathogenesis of endocrine disorders. We move beyond mere correlation to elucidate how gut-derived molecules, such as short-chain fatty acids (SCFAs), secondary bile acids, and indole derivatives, directly and indirectly modulate the hypothalamic-pituitary-gonadal (HPG) axis by modulating the production of neuropeptides and hormones (Gonadotropin-releasing hormone (GnRH)) that regulate reproductive functions and also steroidogenesis and gametogenesis. We examine novel mechanisms including: the epigenetic regulation of steroidogenic enzymes by butyrate; the modulation of enterohepatic circulation of estrogens by β-glucuronidase-producing bacteria; and the role of tryptophan metabolites as ligands for aryl hydrocarbon receptor (AhR) in ovarian and testicular function. Furthermore, we critically appraise the disruptive potential of dysbiosis-driven metabolite shifts in PCOS, endometriosis, and male infertility, highlighting microbial metabolite signatures as promising exploratory biomarkers that require standardized, multi-center clinical validation before diagnostic use. At present, these signatures should be considered candidate biomarkers only, because external validation cohorts, assay reproducibility, and clinically meaningful estimates of sensitivity, specificity, predictive values, and clinical utility have not yet been established. Therapeutically, we evaluate innovative interventions, including precision probiotics, postbiotics, and dietary strategies targeting specific bacterial guilds, but these approaches remain investigational because current human evidence is still limited and heterogeneous. Finally, by integrating microbial endocrinology into reproductive medicine, this review establishes a new framework for understanding the etiology of reproductive endocrine disorders and paves the way for microbiome-targeted therapeutic avenues. Importantly, the evidence base is tiered: mechanistic statements in this review are drawn primarily from in vitro and animal studies, human disease links are described separately as observational evidence, and interventional claims are limited to early clinical studies and randomized trial summaries.

Endometriosis rarely affects the abdominal wall and typically occurs following surgery, like uterine procedures or, more commonly, cesarean sections. There have been a few instances of endometriosis evolving into malignant clear cell carcinoma. Our goal was to examine all relevant cases documented in the literature and introduce a new case. In this article, we analyze reported occurrences of clear cell carcinoma in the abdominal wall and share the case of a 45-year-old woman with a mass on her front abdominal wall. An initial biopsy revealed clear cell carcinoma of the female genital tract. In our facility, she underwent extensive surgery involving the removal of the mass along with sections of the abdominal wall, uterus, fallopian tubes, ovaries, omentum, suspicious lymph nodes, and reconstruction of the abdominal wall using a double-sided mesh. She had a smooth recovery after the operation, but a month later, prior to commencing chemotherapy, she developed metastases in the liver and lungs. She was treated with systemic therapy and, after six months, displayed a positive response with some reduction in the disease. As of 15 months post-surgery, she is doing well under ongoing treatment. Clear cell carcinoma of the abdominal wall is an uncommon and aggressive cancer with a grim outlook. Physicians should be wary of the potential for malignancy in women with an abdominal wall mass and a history of gynecological surgeries, especially cesarean sections.

Postoperative recurrence remains a major obstacle to durable remission in patients with solid tumors, even after complete macroscopic resection. Growing evidence suggests that surgery creates a transient yet highly permissive biological window characterized by inflammatory signaling, coagulation activation, endothelial disruption, and systemic immune suppression. Together, these processes foster a protective niche that enables microscopic residual disease to evade immune surveillance and initiate metastatic outgrowth. Although modern adjuvant therapies have improved outcomes, their effectiveness is often limited by inadequate tumor-site specificity, systemic toxicity, poor immune cell trafficking, and tumor heterogeneity. Consequently, a critical unmet clinical need persists for biologically precise strategies capable of eliminating residual tumor cells at their point of vulnerability. Platelets, traditionally viewed as mediators of hemostasis, are now recognized as active regulators of tumor progression. By facilitating fibrin deposition, shielding circulating tumor cells from immune attack, and shaping inflammatory networks, platelets inadvertently support the survival of postoperative tumors. Paradoxically, these same wound-targeting properties create a compelling therapeutic opportunity: leveraging platelet-driven homing mechanisms to direct immunotherapy precisely to fibrin-rich surgical beds where recurrence often originates. In this review, we propose a platelet-guided CAR-T platform that leverages endogenous wound biology to create a precision immunotherapeutic delivery system. This strategy integrates platelet membrane cloaking or platelet-CAR-T conjugation with thrombin-responsive biomaterial depots to enhance local effector retention, amplify effector-to-target ratios, and prolong functional persistence. Programmable safety features, including affinity tuning, logic-gated activation, and inducible suicide switches, are used to reduce thrombo-inflammatory risk while preserving therapeutic efficacy. These mechanisms restrict activity to appropriate contexts and allow controlled shutdown in case of adverse events, improving overall safety. When coupled with minimal residual disease-guided patient selection using circulating biomarkers, this approach establishes a clinically actionable framework for perioperative intervention. Emerging preclinical evidence suggests that localized platelet-assisted delivery can reduce circulating tumor cell burden, enhance antigen presentation when combined with immune adjuvants, and suppress recurrence more effectively than systemic therapies. With rigorous safety validation, scalable manufacturing, and biomarker-enriched clinical trials, platelet-guided CAR-T therapy has the potential to transform the postoperative microenvironment from a sanctuary of tumor survival into a targeted domain for durable immune-mediated eradication.Clinical trial numberNot applicable.

Endometriosis is a gynecological disease affecting more than 190 million women of reproductive age worldwide, characterized by a complex molecular pathophysiology encompassing genetic, epigenetic, inflammatory, and immunological components. A fundamental methodological challenge in the study of endometriosis is the cellular heterogeneity of ectopic lesions: conventional analysis of bulk tissue specimens reflects averaged molecular profiles of mixed cell populations comprising glandular epithelium, stroma, fibrous and muscular tissue, and immune microenvironmental cells, substantially impeding the identification of cell-specific molecular alterations. This article presents an analysis of the capabilities of laser capture microdissection as a technology for the selective isolation of cell populations from heterogeneous tissues, enabling researchers to overcome this limitation. The methodological principles of the technology are described in detail, including critical parameters of biological material preparation, integration with downstream molecular analysis platforms, and the specificities of protocol standardization and validation across different tissue types. The broad applicability of laser capture microdissection in contemporary biomedical research is reviewed. Particular emphasis is placed on its application in endometriosis research specifically: data on transcriptomic profiling and differential gene expression analysis in the epithelial and stromal components of ectopic lesions are described; studies employing next-generation sequencing aimed at investigating somatic mutations, clonality, and mutational profiles of endometriotic cell populations are reviewed; and work in the field of multi-omics profiling across different disease forms is examined. The review also addresses existing methodological limitations of the technology and prospects for its further development, including integration with spatial transcriptomics, single-cell sequencing, and artificial intelligence-based approaches. Laser capture microdissection constitutes an instrument that opens fundamentally new avenues for investigating the molecular heterogeneity of endometriosis and establishing the foundation for the development of targeted, pathogenetically justified approaches to its diagnosis and treatment. This article also presents the authors’ own experience with the application of laser capture microdissection in endometriosis research. At the time of manuscript preparation, laser capture microdissection had been performed on 15 endometriotic lesion specimens obtained from patients with various forms of endometriosis, with separate isolation of epithelial and stromal components intended for subsequent molecular-genetic analysis.

A endometriose é uma doença inflamatória crônica estrogênio dependente caracterizada pela presença de tecido endometrial fora da cavidade uterina. O diagnóstico combina história clínica, exame físico e, em alguns casos, exames de imagem específicos, apesar de todas essas técnicas o diagnóstico ocorre tardiamente resultando num desfecho desfavorável pelas alterações inflamatórias progressivas. O tratamento tem como objetivo o controle álgico, embora haja demora no acesso ao diagnóstico, desvalorização das queixas, impacto financeiro e dificuldade de estabelecer diagnósticos diferenciais. OBJETIVO: Descrever as barreiras no diagnóstico e tratamento da endometriose. METODOLOGIA: Trata-se de uma revisão de escopo a partir da análise de artigos publicados entre 2020 e 2025, selecionados nas bases de dados SciELO, PubMed e LILACS através da combinação de descritores, cadastrados no DECs, combinados por meio dos operadores booleanos "and" e "or", em português e inglês, disponíveis gratuitamente, que abordaram de forma relevante as barreiras/limitações/desafios no diagnóstico e/ou tratamento da endometriose. O processo se deu a partir da pergunta norteadora "Quais as barreiras para o diagnóstico e tratamento da endometriose em regiões com recursos limitados?", após aplicar os critérios de inclusão e exclusão 17 artigos foram selecionados, os dados foram organizados no PRISMA-ScR e disponibilizados em tabelas/quadros. RESULTADOS: Por meio dos artigos incluídos nos resultados, observou-se que dentre as principais limitações e dificuldades encontradas estão o atraso no diagnóstico e a escolha de um tratamento adequado mediante as individualidades de cada paciente. A normalização dos sintomas, aspectos socioculturais e econômicos, a disponibilidade de exames de imagem também são fatores identificados como importantes. CONCLUSÃO: Observando sua característica inflamatória crônica e diferentes apresentações, a endometriose evidencia um alto nível de complexidade. Assim, estratégias que visem a educação em saúde tanto para pacientes quanto para profissionais, ampliação do acesso de exames diagnósticos e tratamento multidisciplinar devem ser o cerne do manejo para mulheres com endometriose.

Background: Endometriosis and lipedema are chronic female-predominant disorders characterized by persistent pain that is frequently disproportionate to anatomical lesion burden. Although traditionally interpreted within distinct lesion-centered frameworks, both conditions exhibit striking clinical and epidemiological parallels, including hormonally modulated symptom dynamics, overlap with central pain syndromes, weak correlation between structural disease severity and pain intensity, and symptom clustering during reproductive transitions such as puberty, pregnancy, and menopause. Methods: This study aims to synthesize clinical, molecular, neuroimmune, and endocrine evidence on the interrelationship between endometriosis and lipedema, and to propose a hypothesis-generating neuroimmune framework linking both conditions. This integrative narrative review conducted a non-systematic literature search in PubMed/MEDLINE, Scopus, and Web of Science, focusing on mechanisms related to chronic pain, mast cell biology, TRPV1 signaling, CGRP-mediated neurogenic inflammation, intracrine steroidogenesis, and peripheral and central sensitization. Results: The review identifies convergent biological characteristics between the two diseases, including mast cell activation, macrophage polarization, endothelial dysfunction, fibrosis, angiogenesis, intracrine estrogen metabolism, and persistent inflammatory signaling. In endometriosis, direct evidence demonstrates increased sensory innervation, nerve growth factor expression, TRPV1 sensitization, CGRP-positive fibers, and mast cell-nerve interactions. In lipedema, convergent upstream mechanisms, including mast cell infiltration, elevated histamine levels, adipose tissue inflammation, and local estrogen activation, support the plausibility of a functionally analogous neuroimmune organization, despite incomplete direct neural characterization. In this context, the mast cell-TRPV1-CGRP axis is proposed as a biologically plausible framework, directly supported in endometriosis and currently hypothetical in lipedema, connecting peripheral sensitization, neurogenic inflammation, hormonal chronodependence, and central nociceptive amplification. The model further conceptualizes pain crises as transient events of instability within a sensitized neuroimmune network and proposes mechanistic phenotypes that integrate gastrointestinal, inflammatory, central, and hormonal triggers. Conclusion: Endometriosis and lipedema may represent topographically distinct manifestations of a shared neuroimmune process operating within hormone-sensitive tissues. Although the evidentiary basis remains asymmetric, with stronger mechanistic support in endometriosis than in lipedema, this framework provides a biologically plausible and experimentally testable model integrating endocrine, immune, neural, and vascular contributors to chronic pain amplification. This perspective supports coordinated translational investigation across reproductive biology, endocrinology, and pain medicine and may contribute to future mechanism-based stratification and therapeutic development. This work is hypothesis-generating and is not intended to establish causality or to provide clinical recommendations; all proposed mechanistic and therapeutic inferences require prospective experimental validation.

OBJECTIVE: To evaluate central arterial stiffness, endothelial function, and circulating vascular biomarkers in women with ovarian endometriosis and to explore their associations compared with age-matched controls. METHODS: This cross-sectional observational study included women aged 18-40 years with Stage III-IV ovarian endometriosis (n = 20) and age-matched controls without endometriosis (n = 30). Of the 20 women with endometriosis, 18 were receiving Dienogest 2 mg/day at the time of assessment. Central arterial stiffness was assessed using carotid-femoral pulse wave velocity (cfPWV) and aortic Augmentation Index standardized to 75 bpm (AIx@75) using the SphygmoCor® XCEL system. Endothelial function was evaluated by brachial artery flow-mediated dilatation (FMD). Circulating biomarkers including high-sensitivity C-reactive protein (hsCRP), E-selectin, and Endothelin-1 were measured using ELISA. Group comparisons were performed using unpaired t-tests or Mann-Whitney U-tests, and correlations were assessed using Pearson or Spearman analyses. RESULTS: Arterial stiffness parameters did not differ significantly between groups. cfPWV was comparable between women with endometriosis and controls (median [interquartile range] 6.6 [6.0-7.0] vs 6.4 [6.1-6.9] m/s; P = 0.749), as was AIx@75 (24.68% ± 8.71% vs 26.7% ± 12.72%; P = 0.547). However, endothelial function was significantly impaired in women with endometriosis, with lower FMD compared with controls (10.80% ± 3.47% vs 15.26% ± 2.59%; P < 0.001). hsCRP levels were significantly higher in women with endometriosis compared with controls (0.0318 [0.0114-0.0631] vs 0.0105 [0.0062-0.0224] mg/L; P = 0.009), whereas Endothelin-1 levels were significantly lower (15.6 [6.4-32.4] vs 30.6 [18.8-53.6] pg/mL; P = 0.045). E-selectin levels did not differ significantly between groups (P = 0.218). No significant correlations were observed between arterial stiffness indices and molecular markers. CONCLUSION: Women with ovarian endometriosis, the majority of whom were receiving Dienogest therapy, demonstrated impaired endothelial function and elevated systemic inflammation despite preserved central arterial stiffness. These findings support the concept of endometriosis as a systemic inflammatory condition associated with early functional vascular impairment.

Endo-Cycle© (Ендо-Цикл) — це глобальна інтегрована науково-клінічна доктрина та закрита операційна екосистема, що трансформує менеджмент ендометріозу у безперервний протокол довічного захисту соматичного та репродуктивного здоров'я жінки. Вона адаптується до індивідуальних вікових та репродуктивних змін, синтезуючи методи превентивного перехоплення хвороби, епігенетичного захисту гамет та прецизійної хірургії. / Endo-Cycle© is a global integrated scientific-clinical doctrine and closed operational ecosystem that transforms endometriosis management into a continuous protocol for the lifelong protection of a woman's somatic and reproductive health. Ендометріоз — це не локальна хвороба малого таза. Це хронічне, системне, нейроендокринне та імунологічне захворювання, що безперервно змінює біологічний вік жіночого організму (Endo-Age©). Традиційна фрагментована реактивна модель (хірургія + гормональна супресія) ігнорує каскадний патогенез та провокує прискорений Reproaging© і ятрогенне виснаження оваріального резерву. Endometriosis is not a localized pelvic disease. It is a chronic, systemic, neuroendocrine and immunological disorder that continuously alters the biological age of the female organism (Endo-Age©). The traditional fragmented reactive model ignores the cascade pathogenesis and provokes accelerated Reproaging© and iatrogenic ovarian reserve depletion. Українська: Методологічна доктрина «Ендо-цикл©» (V1.0) авторства Вікторії Гудзяк, доктора медичних наук, встановлює безперервну, замкнуту екосистему для довічного клінічного ведення ендометріозу. Відходячи від реактивних хірургічних моделей, вона запроваджує проактивну чотирифазну, що охоплює період від підліткового віку (Endo-Teen Pro-Reserve©) через активний репродуктивний вік (Fertile Endo-Age©) до тривалого збереження органів (Somatic Endo-Age©). Доктрина також кодифікує прецизійний хірургічний протокол Endo-Reserve©, який інтегрує холодний резервний гемостаз для досягнення ендосоматичного тазового мовчання©. Ukrainian: Методологічна доктрина «Endo-cycle©» (V1.0), розроблена д-ром Вікторією Гудзяк, запроваджує безперервну екосистему для довічного клінічного управління ендометріозом. Відмовляючись від реактивних хірургічних моделей, вона впроваджує проактивну чотирифазну структуру: від підліткового віку (Endo-Teen Pro-Reserve©) та активного репродуктивного періоду (Fertile Endo-Age©) до тривалого збереження органів (Somatic Endo-Age©). Доктрина також кодифікує протокол прецизійної операції Endo-Reserve© з інтеграцією гемостазу холодних матриць для досягнення ендо-соматичної тазової тиші.

Background/Objectives: Gastrointestinal (GI) symptoms, including abdominal pain, bloating, altered stool pattern, dyschezia, and nausea, are frequent in women with endometriosis and may persist despite conventional gynecological treatment. The low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (low-FODMAP) diet is an established dietary intervention for irritable bowel syndrome. Its endometriosis-specific evidence base remains limited. This systematic review evaluated clinical evidence on the low-FODMAP diet or structured FODMAP restriction for GI symptoms in women with endometriosis. Methods: This systematic review was prospectively registered in PROSPERO (CRD420261388786) and conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement. PubMed/MEDLINE, EBSCOhost, and BASE were searched from inception to 30 April 2026. Eligible reports were clinical studies investigating low-FODMAP diet or structured FODMAP restriction in women with confirmed, clinically diagnosed, imaging-based, or medically reported endometriosis and extractable GI or related clinical outcomes. Risk of bias was assessed with design-specific tools. Due to substantial heterogeneity across studies in design, comparators, and outcome measures, a narrative synthesis was performed. Results: Five clinical reports met the inclusion criteria: one randomized controlled crossover feeding trial, two prospective non-randomized studies, one retrospective audit of prospectively collected clinic data, and one case report. The randomized trial showed greater GI response during a 28-day low-FODMAP feeding period than during a nutritionally matched control diet. Prospective studies reported improvements in selected GI symptoms, constipation, pain, and quality-of-life domains, but interpretation was limited by non-randomized allocation, attrition, and mixed or pooled diet comparisons. The retrospective audit and case report supported clinical plausibility but were hypothesis-generating. Conclusions: The five available studies, though limited in number and design, indicate that a low-FODMAP diet can reduce GI symptoms in women with endometriosis, particularly those with abdominal pain, bloating, constipation, or IBS-like symptoms. Currently, the low-FODMAP diet should be viewed as a potentially useful, dietitian-guided GI symptom intervention for selected patients. Future trials should define responder profiles, assess long-term tolerability and nutritional safety, and determine the added value of reintroduction and personalization beyond short-term restriction.

BACKGROUND: The prognostic significance of adenomyosis in endometrial cancer (EC) remains controversial. Although several studies have suggested an association between adenomyosis and favorable tumor characteristics or improved survival outcomes, it remains unclear whether this relationship persists after adjustment for established clinicopathologic prognostic factors. AIM: To investigate the impact of coexisting adenomyosis on clinicopathologic characteristics and survival outcomes in patients with endometrioid-type endometrial cancer. METHODS: This retrospective cohort study included 527 consecutive patients with histologically confirmed endometrioid-type endometrial cancer who underwent primary surgical treatment between January 2010 and May 2025 at a tertiary gynecologic oncology center. Patients were categorized according to the presence or absence of adenomyosis identified in hysterectomy specimens. Clinicopathologic characteristics were compared between groups. Disease-free survival (DFS) and overall survival (OS) were evaluated using the Kaplan-Meier method and Cox proportional hazards regression analyses. RESULTS: Adenomyosis was identified in 154 patients (29.2%). No significant differences were observed between patients with and without adenomyosis regarding age, tumor grade, FIGO stage, myometrial invasion, lymphovascular space invasion (LVSI), lymph node metastasis, or adjuvant treatment (all p > 0.05). Kaplan-Meier analysis demonstrated no significant differences in either DFS or OS according to adenomyosis status (log-rank p = 0.626 and p = 0.697, respectively). In multivariable analysis, LVSI remained the only independent predictor of poorer DFS (HR 2.15, 95% CI 1.02-4.53, p = 0.044), whereas older age (HR 1.08, 95% CI 1.06-1.12, p < 0.001), grade 3 histology (HR 2.11, 95% CI 1.26-3.54, p = 0.005), advanced FIGO stage (HR 1.92, 95% CI 1.18-2.93, p = 0.003), and positive peritoneal cytology (HR 4.47, 95% CI 1.20-16.64, p = 0.026) were independently associated with poorer OS. Adenomyosis was not identified as an independent prognostic factor for either DFS or OS. CONCLUSION: In this cohort of patients with endometrioid-type endometrial cancer, coexisting adenomyosis was not independently associated with distinct clinicopathologic features, disease-free survival, or overall survival. Established clinicopathologic factors remained the primary determinants of oncologic outcomes.

Bowel involvement is a severe manifestation of deep endometriosis that affects approximately 8-12% of women with endometriosis. Bowel endometriosis is most commonly localised in the rectosigmoid colon and frequently coexists with other pelvic lesions. The pathogenesis of bowel endometriosis is multifactorial, involving hormonal, inflammatory, immune, genetic, and anatomical factors. Clinical presentation ranges from asymptomatic disease to severe gastrointestinal and pelvic symptoms, which can mimic other digestive disorders such as irritable bowel syndrome and inflammatory bowel disease. Diagnostic delays frequently exceed 7-10 years. Transvaginal ultrasound and MRI are the main non-invasive tools for the diagnosis and preoperative assessment of rectosigmoid endometriosis. First-line medical therapy with combined oral contraceptives or progestogens might provide symptom control but is not curative, whereas surgery is reserved for bowel obstruction or severe or refractory symptoms, with surgical approach tailored to disease characteristics and patient needs. Fertility outcomes remain uncertain, and the complexity of long-term management, including the rare risk of malignant transformation, supports the need for multidisciplinary follow-up.

(No abstract on file for this paper.)

BACKGROUND: Endometriosis is sustained by ectopic endometrial implants that remain proliferative and vascularized, making endocrine modulation a cornerstone of therapy. Estetrol (E4) an endogenous estrogen produced during pregnancy, with selective tissue activity, may modulate progesterone (P4) outputs in ectopic tissue and potentially shift lesion biology toward growth restraint without reinforcing vascular support. OBJECTIVE: To test whether E4 modifies P4 effects on lesion proliferation, apoptosis-related signaling, and angiogenic/endothelial activation in vivo. METHODS: Hormonally intact female mice bearing allografted endometriotic lesions received vehicle, E4 (3 mg/day), P4 (4.25 mg/day), or E4 + P4 once daily for 14 days. Lesions and eutopic endometrium were assessed by immunohistochemistry (Ki-67, cleaved caspase-3, BAX, VEGF, PECAM-1/CD31, Cyclin D1) with epithelial/stromal quantification, and endothelial angiogenic behavior was evaluated using a tube-formation assay. RESULTS: Lesions exhibited higher proliferative activity than eutopic endometrium. P4 reduced lesion proliferation, and the E4 + P4 combination produced the strongest growth restraint. Apoptosis-related markers increased under endocrine treatments, with the combined regimen showing robust activation. Notably, P4 enhanced angiogenesis-related readouts (VEGF and PECAM/CD31), whereas E4 + P4 prevented these increases and reduced endothelial tube formation, consistent with attenuated endothelial activation under the combined regimen. CONCLUSIONS: The E4-P4 combination supports a "balanced" endocrine profile-robust growth restraint without concurrent endothelial activation-thereby decoupling proliferation restraint from angiogenic activation.

Cardiovascular disease (CVD) remains the leading cause of mortality in women, yet sex-specific risk factors are usually not included in conventional predictive models. Specifically, heart failure (HF) in women may be influenced by sex-specific hormones and pathologies that need to be addressed to improve prevention and treatment. This expert consensus statement aims to provide a comprehensive roadmap for HF prevention and management across specific conditions affecting women during their life-course. Each section focuses on the impact of a specific female condition on CVD and how to prevent and manage HF in specific settings: 1. Pregnancy with a specific focus on how to deal with hypertensive disorders in the acute and chronic setting and how to prevent and treat Peripartum Cardiomyopathy (PPCM); 2. Gynecological conditions predisposing to HF, such as Polycystic Ovary Syndrome (PCOS), endometriosis, and the menopausal transition. Emphasis is placed on chronic inflammation, metabolic dysfunction, and the "window of opportunity" for Menopausal Hormone Therapy (MHT); 3. Cardio-Oncology: mitigating Cancer Therapy-Related Cardiac Dysfunction (CTRCD) in breast and gynecological cancers, focusing on female-specific cardiotoxicity profiles, the importance of subclinical detection of cardiac dysfunction and the implementation of cardioprotective strategies (ACE-inhibitors, Beta-blockers, SGLT2 inhibitors) during cardiotoxic treatments. Lifestyle interventions such as the DASH diet and exercise-based rehabilitation are highlighted as essential for maintaining cardiac reserve.

BACKGROUND: Early-life exposures may influence long-term reproductive health, but comprehensive population-based evidence remains limited. This study aimed to evaluate the associations between six early-life factors (long-term/recurrent antibiotic use [LRAU], birth weight, multiple birth, breastfeeding, age at menarche and maternal smoking around birth) and the risk of six major non-neoplastic gynecological diseases in adulthood. METHODS: This large observational association study used data from 272,706 women derived from the UK Biobank, a population-based cohort resource. Six gynecological disorders-uterine fibroids (UF), polycystic ovary syndrome (PCOS), endometriosis, genital prolapse, female infertility, and premenstrual syndrome (PMS)-were identified from hospital inpatient records, first occurrence records, and self-reports. Multivariable logistic regression was used as the primary analysis to estimate adjusted odds ratios (aORs), with Cox models as supplementary analyses. The primary adjusted model included age at recruitment, ethnicity, educational attainment, Townsend deprivation index, and smoking status. A Bonferroni-adjusted significance threshold of P < 0.0014 was applied. RESULTS: Among 272,706 women, the prevalence of the six non-neoplastic gynecological diseases ranged from 0.07% for PMS to 8.51% for UF. After Bonferroni correction, LRAU during early life was associated with higher odds of UF, PCOS, endometriosis, genital prolapse, and PMS. Earlier menarche was associated with higher odds of UF, PCOS, endometriosis, and genital prolapse. Maternal smoking around birth was associated with endometriosis, genital prolapse, and PMS. Not being breastfed as a baby was associated with endometriosis and PMS. Birth weight was associated with genital prolapse. Findings were generally consistent across Cox models and sensitivity analyses, although PMS estimates should be interpreted cautiously because of limited cases. CONCLUSIONS: These findings suggest associations between selected early-life factors and adult non-neoplastic gynecological diseases. Some exposures are potentially modifiable, whereas others are non-modifiable. Together, these factors may help identify individuals at higher risk and inform future studies on risk stratification, but their potential preventive implications require further causal validation.

Background: The surgical management of chronic pelvic pain (CPP), particularly in endometriosis, often focuses on lesion excision or nerve decompression. However, persistent pain frequently occurs despite “anatomical perfection,” suggesting central nervous system involvement. Neuropelveology faces a “surgical paradox” when dealing with central sensitization (CS), where peripheral interventions fail to address a systemic nociplastic state. Methods: This systematic review followed PRISMA guidelines and was registered in PROSPERO (CRD420261335008). A search across PubMed, Embase, and Cochrane (2010–2026) identified 71 relevant studies involving over 12,000 participants. Results: CS prevalence in the endometriosis population ranges from 11.3% to 58.2%, rising to 74.8% in specialized tertiary referral centers. The Central Sensitization Inventory (CSI) is a robust predictor of surgical failure; every one-point increase in preoperative CSI raises the risk of persistent pain (OR 1.02, p = 0.02). Objective markers, such as the collapse of Conditioned Pain Modulation (CPM), confirm that “high-sensitizers” (CSI ≥ 40) suffer from a systemic “software” failure of pain inhibition. Conclusions: We propose a paradigm shift in neuropelveology. In patients with high CSI scores (≥40), functional neuromodulation—specifically the LION procedure—should be prioritized over traditional nerve decompression to address the nociplastic nature of the pain.

Personal health tracking technologies are commonly designed around cisnormative and binary assumptions, limiting their usefulness and safety for transgender and gender-diverse (TGD) individuals. This paper investigates how TGD people with endometriosis engage with existing health-tracking tools and the barriers they encounter in doing so. We report findings from an online questionnaire (n=34) exploring lived experiences, self-tracking practices, and perceptions of exclusion. Our results highlight a set of design tensions in current tools, including privacy and disclosure concerns, gendered designs, reductionist symptom models, and an emotional burden associated with tracking. We argue for more inclusive, gender-affirming approaches to self-tracking and present this work as a provocation for researchers and designers to rethink how identity and embodied experiences are encoded in self-tracking technologies.

Endometriosis is a chronic inflammatory and fibrotic condition in 1 in 10 women characterized by the abnormal growth of endometrial tissue outside of the uterus. Endometriotic tissues attach to the peritoneal mesothelium lining the pelvic cavity to establish harmful lesions and implants in ectopic sites, leading to pelvic pain, infertility, and reduced quality of life. Dysregulated behaviors such as cell migration, invasion, proliferation, and immune escape drive lesion formation. The endometriotic microenvironment contributing to these cell behaviors is complex, with notable components including high local levels of estradiol (E2), a potent estrogen molecule, fibrotic extracellular matrix stiffening, inflammatory markers, and diverse cellular interactions. However, dynamic cellular processes in endometriosis are still not well understood. Moreover, the field is understudied and would benefit from more accessible, diverse, and physiologically relevant in vitro models. This dissertation investigates how hormonal and mechanical microenvironmental cues regulate dynamic cellular processes during endometriosis progression using accessible in vitro models. Our first focus is on hormonal signaling, as E2 has been widely implicated in endometriosis pathogenesis. Whether commonly used cell culture models faithfully capture E2-driven migratory phenotypes, and how hormonal cues interact with the physical properties of the microenvironment, remain open questions. This work first examines the effects of E2 on actin organization, morphodynamic flexibility, and migratory behavior in an endometriotic epithelial cell line (12Z), with the goal of validating its hormone responsiveness. Unexpectedly, E2 sensitivity was found to be context-dependent, motivating a broader investigation into additional microenvironmental regulators of cell behavior. Our subsequent studies focus on the role of mechanical tissue stiffening during fibrosis, using polyacrylamide gels to model healthy and pathological matrices. We demonstrate that substrate stiffness regulates epithelial motility, cytoskeletal organization, and collective migration. We then develop an in vitro model of endometriotic implantation into the mesothelium and show that endometriotic spheroids preferentially disrupt mesothelial barriers on glass, while fibrotic stiffness produces graded effects. By characterizing hormone responses and integrating mechanobiology into co-culture in vitro systems, this dissertation advances our understanding of early lesion establishment. This work also informs future in vitro model design and provides tools for more physiologically informed endometriosis research.

Abstract Background Endometriosis, defined by the abnormal growth of endometrial-like tissue outside the uterus, impacts 6–10% of women of reproductive age and is a significant contributor to infertility. The Estrogen Receptor 1 ( ESR1 ) gene is integral to estrogen-dependent signalling pathways, and variations in this gene have been associated with an increased susceptibility to endometriosis. Methods This study investigated the relationship between two polymorphisms in the ESR1 gene (rs9340799 and rs2234693) and infertility associated with endometriosis in South Indian women. The research involved three groups: infertile women diagnosed with endometriosis, infertile women without the condition, and fertile women serving as controls. Genotyping was performed using PCR, and statistical analyses assessed genotype distributions. Additionally, in silico analyses were conducted using GeneMANIA and STRING to examine ESR1 -related gene–gene and protein–protein interaction networks. Results Among the 163 subjects studied, no significant association was observed between either ESR1 SNP and infertility related to endometriosis across all genetic models. In silico analysis revealed that ESR1 participates in biologically meaningful networks, interacting with multiple genes and proteins involved in hormonal signalling, transcriptional regulation, and reproductive functions, supporting its functional relevance in endometriosis pathways. Conclusion Although ESR1 variants rs9340799 and rs2234693 were not statistically associated with endometriosis-related infertility in this population, bioinformatics analyses underscored ESR1 's role in regulatory networks related to estrogen signalling. These findings warrant further large-scale and functional studies integrating both genetic association and molecular pathway data to better understand ESR1 's contribution to endometriosis.

(No abstract on file for this paper.)

No direct evidence for the management of vaginal endometriosis was identified. Current understanding draws upon broader endometriosis management strategies, where a combination of surgical and pharmacological interventions, such as using LNG-IUS post-surgery, shows potential to manage symptoms and reduce recurrence, although additional targeted research is needed.

OBJECTIVE: The aim of this study was to characterize recurrence patterns, identify clinicopathologic prognostic factors associated with overall survival and disease-free survival, and determine the independent prognostic significance of adenomyosis in surgically treated endometrial carcinoma. METHODS: This retrospective single-center cohort included 868 patients who underwent primary surgical treatment for histopathologically confirmed endometrial carcinoma. Clinicopathologic characteristics, recurrence patterns, treatment modalities, and survival outcomes were analysed. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Multivariable Cox regression models included age at diagnosis, FIGO stage, histologic type, and adenomyosis. Additional endometrioid-only subgroup and surgery-period sensitivity analyses were performed. RESULTS: During follow-up, recurrence occurred in 211 patients (24.3%). Recurrence was significantly more frequent in non-endometrioid tumors and increased progressively with advancing FIGO stage and tumor grade (all p < 0.001). In multivariable analysis, increasing age, advanced FIGO stage, and non-endometrioid histology were independently associated with poorer OS. Age and FIGO stage also independently predicted DFS. Adenomyosis was associated with lower unadjusted recurrence rates; however, after adjustment, it was not independently associated with OS and showed only a borderline association with DFS. Similar recurrence patterns were observed in the endometrioid-only subgroup, and surgery-period sensitivity analysis demonstrated consistent prognostic associations across different treatment eras. CONCLUSION: FIGO stage, age, and histologic type remain the major determinants of survival in endometrial carcinoma. While adenomyosis was associated with more favorable unadjusted outcomes, its independent prognostic value appears limited after accounting for established clinicopathologic factors. These findings support the continued importance of classical risk factors and highlight the need for future studies integrating molecular classification to better define the prognostic role of adenomyosis.

Recent studies have highlighted the crucial role of mechanical properties in the ovarian microenvironment for ovarian function. However, the mechanisms that cause ovarian matrix stiffening during aging remain incompletely understood. Here we utilized atomic force microscopy (AFM) to demonstrate that human ovarian matrix stiffness increases with aging and in pathophysiological conditions, such as chemotherapy-induced premature ovarian insufficiency (POI), polycystic ovary syndrome (PCOS) and ovarian endometriosis. By integrating proteomic analysis of human ovarian tissue with transcriptomic profiling of human ovarian fibroblasts, we identified that IL-11, which is elevated in aging ovaries of mice, rats and humans, activates fibroblasts to secrete extracellular matrix (ECM), thereby increasing ovarian matrix stiffness. Genetic deletion of Il11ra1 in mice mitigated the increase in ovarian matrix stiffness and the decline in ovarian function associated with aging, chemotherapy-induced POI and PCOS. Single-nuclei RNA sequencing (snRNA-seq) revealed that blocking Il11ra1 reduces the proportion of activated fibroblasts. Furthermore, administration of siIl11 nanoparticles to aged mice and rats enhanced fertility and reduced ovarian matrix stiffness. Together, these findings highlight the pro-inflammatory factor IL-11 in regulating ovarian matrix stiffness. We propose that anti-IL-11 therapy represents a promising translational strategy for delaying ovarian aging.