Endometriosis is an inflammatory estrogen-dependent disorder characterized by pain, dyspareunia, dysmenorrhea, and infertility. This is due to the invasion of different organs by endometrial tissue that causes inflammation, angiogenesis, and fibrosis. The ion channels Piezo1 and Piezo2 primarily work as mechanosensors and mechanotransducers but also have functions that could participate in the clinical hallmarks of endometriosis. Thus, we investigated the occurrence and localization of Piezo1 and Piezo2 in healthy human endometrium and in endometriosis using immunohistochemistry. In healthy endometrium, Piezo1 immunoreactivity was detected in the glands and to a lesser extent in the stroma; Piezo2 was present in the same locations but at low or residual levels. In ectopic endometriosis, there was an increase in the intensity of Piezo1 regardless of location; Piezo2 only showed a net increase in the ovarian and vaginal endometriosis foci. The present results demonstrate the occurrence of Piezo ion channels in the healthy human endometrium for the first time, as well as an increase in Piezo1 in ectopic endometriosis, and no changes in Piezo2 with the exception of the ovary and vagina. However, these results are descriptive and qualitative, although they may serve as the basis for further studies. The role of these ion channels in the endometrium and in the pathogenesis of endometriosis remains to be elucidated, and more precise methods are needed to follow up on this pilot study that can be better analyzed statistically to confirm the results.

Microplastics and nanoplastics (MNPs) have emerged as ubiquitous environmental contaminants that are increasingly detected in human biological matrices, including blood, urine, placenta, and reproductive tissues [1–3]. Due to their small size, persistence, and physicochemical properties, these particles are capable of entering the human body through ingestion and inhalation, followed by systemic distribution [4]. Endometriosis is a chronic, estrogen-dependent inflammatory disease affecting approximately 10% of women of reproductive age and is characterized by immune dysregulation, oxidative stress, mitochondrial dysfunction, and altered hormonal signaling [5–7]. Growing evidence indicates that exposure to environmental pollutants may modulate molecular pathways relevant to the development and progression of endometriosis [8]. Experimental studies demonstrate that MNPs can induce oxidative stress, activate inflammatory signaling cascades, disrupt endocrine function, and alter immune cell behavior—mechanisms that overlap with the established pathophysiology of endometriosis [9–12]. Recent reports describing the presence of microplastics in human endometrial tissue further raise concerns regarding direct tissue-level exposure [13]. This narrative review summarizes current PubMed-indexed evidence on human exposure to microplastics and nanoplastics, their biological effects relevant to female reproductive health, and the mechanistic plausibility of their involvement in endometriosis pathogenesis, while highlighting existing knowledge gaps and methodological limitations.

Endometriosis is traditionally conceptualized as a pelvic lesion–centered disease; however, mounting evidence indicates it is a chronic, systemic, and multifactorial inflammatory disorder. This review examines the molecular dialog between ectopic endometrial tissue, the immune system, and peripheral organs, highlighting mechanisms that underlie disease chronicity, symptom variability, and therapeutic resistance. Ectopic endometrium exhibits distinct transcriptomic and epigenetic signatures, disrupted hormonal signaling, and a pro-inflammatory microenvironment characterized by inflammatory mediators, prostaglandins, and matrix metalloproteinases. Immune-endometrial crosstalk fosters immune evasion through altered cytokine profiles, extracellular vesicles, immune checkpoint molecules, and immunomodulatory microRNAs, enabling lesion persistence. Beyond the pelvis, systemic low-grade inflammation, circulating cytokines, and microRNAs reflect a molecular spillover that contributes to chronic pain, fatigue, hypothalamic–pituitary–adrenal axis dysregulation, and emerging gut–endometrium interactions. Furthermore, circulating biomarkers—including microRNAs, lncRNAs, extracellular vesicles, and proteomic signatures—offer potential for early diagnosis, patient stratification, and monitoring of therapeutic responses. Conventional hormonal therapies demonstrate limited efficacy, whereas novel molecular targets and delivery systems, including angiogenesis inhibitors, immune modulators, epigenetic regulators, and nanotherapeutics, show promise for precision intervention. A systems medicine framework, integrating multi-omics analyses and network-based approaches, supports reconceptualizing endometriosis as a systemic inflammatory condition with gynecologic manifestations. This perspective emphasizes the need for interdisciplinary collaboration to advance diagnostics, therapeutics, and individualized patient care, ultimately moving beyond a lesion-centered paradigm toward a molecularly informed, holistic understanding of endometriosis.

Fibroblast activation protein inhibitor (FAPI) PET is an emerging molecular imaging modality that is widely used in oncology and increasingly investigated in nononcologic diseases. Abdominal wall endometriosis (AWE) is a rare form of endometriosis, characterized by ectopic endometrial tissue in the abdominal wall. We present a patient with a right external obturator mass, biopsy-confirmed as endometriosis, in whom 68Ga-FAPI-04 PET/CT revealed extensive multifocal AWE and adenomyosis. These lesions demonstrated intense FAPI uptake, in contrast to their low or absent FDG uptake. This case highlights the potential of FAPI PET for detecting atypically located endometriosis, a capability lacking in current imaging methods.

Endometriosis is a widespread gynecological condition characterized by the presence of endometrial like tissue outside the uterine cavity. According to the literature, the frequency of endometriosis in adolescents remains unclear; however, studies suggest that histologically confirmed disease may be present in up to 47% of girls with chronic pelvic pain (CPP) and in nearly 70% of girls with primary dysmenorrhoea unresponsive to nonsteroidal anti-inflammatory drugs (NSAIDs) or hormonal therapy. The aim of this study was to review and compare current diagnostic and therapeutic recommendations and expert consensus for adolescent endometriosis. A descriptive qualitative review of the clinical guidelines and expert consensus statements by the American College of Obstetricians and Gynecologists (ACOG), the European Society of Human Reproduction and Embryology (ESHRE), the North American Society for Pediatric and Adolescent Gynecology (NASPAG), and the Polish Society of Gynecologists and Obstetricians (PTGiP) was conducted. NASPAG guaidance present a textbook-based expert consensus and was included due to the limited availability of high-quality evidence in adolescent populations. Adolescent endometriosis remains underrecognized and insufficiently studied. Current clinical guidelines and expert consensus statements emphasize the importance role of through symptom assessment and detailed medical history in the diagnostic process. The reviewed literature supports a clinical diagnosis based on symptoms presentations and response to hormonal therapy, without routine laparoscopic confirmation. Endometriosis in adolescents requires an age-specific diagnostic and therapeutic process. Adherence to current clinical guidelines and expert consensus may help reduce diagnostic delays, limit unnecessary invasive procedures, and improve long-term quality of life.

Endometriosis (EM) is an inflammatory condition that affects approximately 10% of the female-born population. It is characterized by the presence of endometrial tissue outside the uterine cavity, leading to chronic pelvic pain, dysmenorrhea, infertility, and a significant reduction in quality of life. The molecular feature of endometriosis remains poorly understood. Endometriosis-related transcriptomic datasets from the Gene Expression Omnibus (GEO) were normalized and analyzed, and candidate hub genes were identified using two machine learning algorithms. These protein expressions were further validated using proteomic data derived from clinical ectopic and eutopic endometrial tissue samples. Functional assays, including gene silencing and cell migration experiments, were conducted to investigate their biological roles. Glutathione Peroxidase 3 (GPX3) emerged as a candidate diagnostic protein. Silencing GPX3 significantly reduced the migratory capacity of endometriosis cells, likely through modulation of antioxidant activity. In clinical samples, ectopic lesions with high GPX3 expression exhibited increased immune cell infiltration, particularly showing elevated CD68⁺ macrophages and PD-1-positive T cells. Collectively, our findings suggest that GPX3 serves as a potential biomarker for the diagnosis and prognosis of endometriosis, with its expression positively correlating with immune cell infiltration in ectopic endometrial tissue.

BackgroundEndometrial receptivity (ERE) is a transient uterine state that determines the success of blastocyst implantation; however, the epigenomic regulation underlying ERE establishment in goats remains unclear. Here, we profiled transcriptional and epigenomic features of endometrial tissues from pregnant goats during the peri-implantation window and nonpregnant control goats in the regressed luteal phase to uncover the transcriptional regulatory networks responsible for ERE establishment in goats, utilizing RNA-seq, ATAC-seq, and H3K27ac CUT&Tag.ResultsA total of 3,143 differentially expressed genes (DEGs) were identified, accompanied by significant alterations in chromatin accessibility and H3K27ac modifications between receptive and non-receptive endometria. The targeted genes associated with these epigenetic changes were significantly enriched in pathways related to cell adhesion, immune tolerance, and embryo attachment. Motif enrichment and transcription factor (TF) footprinting analyses identified members of the FOS/JUN, SOX, HNF1, CEBP, and BATF families as candidate regulators, implicating downstream genes involved in ERE establishment, including SPP1, FOXO1, KLF4/6, STAT1, IFI6, ITGB8, PLAC8, DUSP4, NR1D1, ISG15, RUFY4, and PIK3R3. In addition, numerous super-enhancers were identified, indicating regions of high regulatory activity and potential long-range gene-enhancers interactions in the endometrium. Integration of multi-omics datasets revealed a strong correlation (r > 0.7) among chromatin accessibility, H3K27ac activation, and the expression of 172 DEGs. Furthermore, a set of hub genes (KLF6, IFI6, MCL1, SDC4, SUSD6, MAFF, and IL6R) that appear to coordinate TF binding and distal super-enhancers activity associated with ERE establishment.ConclusionsOur data provided an integrated epigenomic atlas of endometrial receptivity establishment in goats and identify candidate regulatory elements and transcription factors that may orchestrate uterine preparation for implantation. These findings offer valuable insights and testable targets for improving fertility in ruminant livestock.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40104-025-01318-2.

Endometriosis and adenomyosis are prevalent chronic inflammatory conditions that significantly impact reproductive-age women, leading to debilitating symptoms such as pelvic pain, dysmenorrhea, and infertility. Endometriosis is characterized by ectopic endometrial tissue outside the uterus, while adenomyosis involves endometrial deposits within the myometrium, often causing overlapping symptoms. Accurate diagnosis is essential for effective management, yet challenges persist due to variability in lesion location and presentation. Imaging plays a crucial role in the diagnosis, staging, and management of these conditions. While transvaginal ultrasound (TVUS) remains a reliable first-line tool with high specificity, magnetic resonance imaging (MRI) offers superior sensitivity, particularly for endometriomas and deep endometriosis. Both modalities have their limitations but are complementary in preoperative assessment and treatment planning. Emerging imaging protocols, classification systems, and advancements such as dynamic TVUS and improved MRI techniques are discussed. Despite significant progress, the lack of a universally accepted classification system and standardized imaging protocols highlights the need for further research. Advancing diagnostic accuracy and treatment strategies through imaging holds promise for improving patient outcomes. This article reviews the pathophysiology, staging and subtypes of endometriosis and adenomyosis. Recent society guidelines are addressed and readers are provided with updates on imaging technologies with insights into future directions.

Ginsenoside Rg3 antagonises endometriosis glycolysis via the tripartite motif containing 28 and pyruvate dehydrogenase kinase 4 signalling pathway.

The aim of this study was to develop an advanced in vitro model of human endometrium using single-cell derived endometrial epithelial organoids, enabling the study of embryo secretome-endometrial crosstalk at the maternal-fetal interface. Single-cell derived organoids generated from endometrial tissue of a parous 39-year-old woman recapitulated hormone-responsive decidualization, as demonstrated by expression of SPP1 and acetyl-α-tubulin. When cultured in embryo culture media, organoid viability was maintained with no cytotoxicity, but proliferation was suppressed, likely due to the lower concentrations of the required factors in organoid growth media. Organoids were stimulated with culture supernatants from morphologically good-quality embryos with known pregnancy outcomes (live birth (n = 4) versus no pregnancy (n = 4)). Transcriptomic profiling (RNA-sequencing) revealed that 32 genes were differentially expressed (DEGs) in organoids exposed to the culture supernatants from live-birth embryos versus non-pregnant outcomes: 24 upregulated and 8 downregulated. These DEGs were enriched for biological processes related to cell motility and cytoskeletal dynamics. In conclusion, soluble factors secreted by human blastocysts achieving live birth selectively modulate the endometrial epithelial transcriptome, enhancing pathways involved in cytoskeletal remodeling and immune modulation. This embryo-directed remodeling likely facilitates endometrial receptivity for successful implantation to occur. Our organoid model provides a robust platform for further investigating implantation failure.

FTIR Spectroscopy Combined with Machine Learning Reveals Molecular Signatures Distinguishing three Phenotypes of Endometriosis.

In 2020, 128.5 million new chlamydia infections were reported worldwide in adults aged 15–49 years. Notably, the prevalence of Chlamydia trachomatis infection in pregnant women varies between 2% and 35%, correlating with increased risks of low birth weight, preterm birth, and neonatal death. C. trachomatis is a leading preventable cause of miscarriage. Recurrent first-trimester pregnancy loss can be induced by asymptomatic chlamydia infection through the immune response. In this study, we performed immunohistochemical characterization of the immune response in endometrial tissue biopsies from women diagnosed with chronic endometritis caused by C. trachomatis. Hematoxylin and eosin staining was used for histological evaluation of endometrial biopsies, and immunohistochemical detection was performed for the following markers: CD138, CD45, CD3, CD4, CD8, CD20, CD56, and CD68. As a result, we observed the presence of edematous tissue with hemorrhage; we also observed a heightened inflammatory response with the presence of plasma cells, CD4 and CD8 T lymphocytes, B lymphocytes, NK cells, and macrophages. The findings described here can help better understand the disease and its histopathological diagnosis.

Endometrial cancer (EC) is the most common gynecological malignancy, yet reliable screening and diagnostic approaches remain limited. We developed a weakly supervised deep multi-instance learning model (DSMIL) to classify hematoxylin and eosin-stained whole-slide images (WSIs) of endometrial tissue. A total of 885 WSIs from 442 patients, including EC, atypical endometrial hyperplasia (AEH), endometrial hyperplasia without atypia (EH), and normal endometrium (NE), were analyzed. DSMIL achieved an average AUROC of 0.9776 for four-class classification, with inter-class AUROCs of 0.9876 for EC, 0.9600 for AEH, 0.9771 for EH, and 0.9855 for NE, and outperformed other algorithms such as TransMSL, CLAM, and ABMIL (average accuracy = 0.8914). Attention heatmaps highlighted regions associated with pathological features, while nnU-Net v2 combined with HoverNet enabled identification of atypical glandular epithelial cells, which showed increased density, size, and perimeter but reduced axis ratios compared with normal cells. These results suggest that DSMIL provides a reliable computational pathology approach for the classification of endometrial lesions and the characterization of atypical cells.

Nearly a century has passed since a seminal review article was published in 1928 in Archives of Pathology on ectopic endometriosis, presenting the dominant pathogenetic theories of the era: the serosal theory suggesting that endometriosis would arise by metaplasia of the peritoneal mesothelium; the metastatic theory implying the role of uterine lymphovascular invasion by endometrial tissue; and the implantation theory. Since then endometriosis has been the subject of numerous studies due to the associated morbidity and its significant impact on patients' quality of life and health care costs. To provide an overview of our evolving understanding of pathogenesis and clinicopathologic features of endometriosis. Review of the literature and personal experience of the authors. The prevailing pathogenetic theory of endometriosis remains the retrograde menstruation and implantation theory proposed by Sampson in the 1920s. Contemporary studies have focused on the additional role of inherited genetic components, a supportive microenvironment, and molecular genetic alterations to improve the clinical classification, prognostication, and therapeutic options for patients with endometriosis.

Ovariectomy induces regression of hyperplastic uterus in female dogs.

Adenomyosis remains a challenging gynecological disorder to investigate due to the absence of in vitro models that accurately replicate endometrial tissue dynamics across the menstrual cycle. To address this gap, we established an endometrial assembloid model that faithfully mimics cycle-dependent endometrial responses and captures key cellular and molecular hallmarks of adenomyosis, including ectopic lesion- specific epithelial and stromal heterogeneity. Single-cell transcriptomics revealed that ectopic epithelial cells shift toward a luminal- dominant, glandular-deficient transcriptional profile during the secretory-like phase. This transition correlated with ectopic stromal reorganization-specifically, loss of BMP4+ stromal cells and an accumulation of CRYAB+IL15+ stromal cells-which impaired BMP-mediated stromal-epithelial signaling while enhancing WNT activation. Additionally, ectopic epithelial and stromal cells demonstrated increased immunity and angiogenesis activities. Our assembloid platform not only provides a physiologically relevant model for investigating adenomyosis pathogenesis but also implicates aberrant WNT signaling as a potential therapeutic target, offering new opportunities for mechanism-driven treatment strategies.

Endometriosis (EMS), a multifactorial and chronic benign gynecological disease characterized by ectopic endometrial growth, remains poorly understood in its pathogenesis. Proline, glutamic acid, leucine-rich protein 1 (PELP1), implicated in various diseases, has not been studied in EMS. Here, we investigated the functional role and molecular mechanisms of PELP1 in EMS progression. Using ectopic and eutopic endometrial tissues from EMS patients, we showed that PELP1 was significantly upregulated in ectopic lesions. Knockdown of PELP1 in primary ectopic endometrial stromal cells (Ec-ESCs) and the mouse model inhibited proliferation, angiogenesis, and inflammation. Mechanistically, PELP1 interacted with FHL2 to potentiate transcriptional activation of downstream factors, such as CCND1, CCND2, CDK6, ANG, CCL2, and MMP3. These findings demonstrate that PELP1 promotes EMS progression and highlight its potential as a novel therapeutic target.

Endometriosis lesion growth inhibition and immune modulation function of thymol in vitro and in vivo.

Targeting the mPGES-PGE2-EP4 pathway with MF63, MK886, and Grapiprant as a potential therapeutic strategy for Escherichia coli-induced endometritis in dairy cows.

Background Although most cases of endometrial cancer (EC) are diagnosed at an early stage with favourable outcomes, the prognosis for advanced or recurrent disease remains poor, highlighting the need for novel therapeutic targets. This study aimed to examine the correlation between Cyclin B1 (CCNB1) and Cyclin B2 (CCNB2) expression and disease severity in EC through bioinformatics analysis. Methods Common differentially expressed genes were identified in two EC cohorts from the Gene Expression Omnibus. A protein-protein interaction (PPI) network was constructed to identify hub genes. Aberrant expression of the hub genes was validated in external datasets. Their prognostic values were evaluated in a cohort from The Cancer Genome Atlas (TCGA). Knockdown of the hub genes was conducted to explore their functions in the malignant behaviour of EC cells in vitro. Results CCNB1 and CCNB2 were identified as the top 2 hub genes in the PPI network. High CCNB1/CCNB2 expression was significantly associated with shorter survival in EC patients. Overexpression of CCNB1/CCNB2 in endometrial tumour tissue was validated in public datasets. In TCGA cohort, high expression of CCNB1/CCNB2 correlated with greater disease severity and predicted poor prognosis. In addition, high expression of CCNB1/CCNB2 was strongly associated with immune cell infiltration, as well as increased expression of immune checkpoint genes and mismatch repair genes. Furthermore, knockdown of CCNB1/CCNB2 significantly suppressed the proliferation, migration, and invasion of HEC-1 and Ishikawa cells in vitro. Conclusions CCNB1 and CCNB2 may serve as potential prognostic markers and therapeutic targets for the management of EC.