Search Results (924)

Background: Primary endometrial lymphomas (PELs) are exceedingly rare and diagnostically challenging lesions. Objective: To assess the clinicopathologic features of PELs. Methods: We adhered to the PRISMA-2020 guidelines for reporting systematic reviews. A PubMed literature search (1956–2025) was conducted using keyword combinations including “endometrium” and “lymphoma,” “lymphoid proliferation,” or “lymphoproliferative lesions.” Only original articles published in the English peer-reviewed journals were considered. The inclusion criteria were: (i) studies involving human subjects, and (ii) studies published in the English language. Reviews, editorials, meeting abstracts, and non-English publications were excluded. Results: We identified 42 studies for our analysis, collectively reporting 58 cases of PELs. Abnormal uterine bleeding was the main complaint. Non-Hodgkin lymphoma (57 cases) and Hodgkin lymphoma (one case) were identified. In most cases, lymphoma was the sole lesion. In five cases, lymphoma coexisted with, preceded, or followed endometrial carcinoma. Histologically, PELs either diffusely involved the endometrium (50 cases) or were localized to endometrial polyps (eight cases). Marginal zone lymphoma (MZL) was the most frequently reported type, followed by diffuse large B-cell lymphoma (DLBCL). Other rare types included intravascular large B-cell lymphoma, NK/T-cell lymphoma, T-cell lymphoma, and low-grade B-cell lymphoma. Conclusions: Our study indicates that MZL and DLBCL were the most common types of PELs. Other extremely rare subtypes were also identified. Moreover, some PELs developed in the background of endometrial polyps and, in exceptional cases, in association with endometrial carcinoma. Radiological findings were critical for provisional diagnosis, staging, and follow-up. Key modalities included ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), and 18F-fluoro-2-deoxyglucose positron emission tomography/CT (18F-FDG PET/CT). Full article

Endometriosis is a chronic hormone-responsive disorder linked to infertility, usually characterized by the presence of ectopic endometrium in the pelvis that disrupts local homeostasis. Advances in single-cell “omic” methods have revealed the remarkable cellular diversity within the eutopic endometrium and endometriosis lesions, uncovering distinct populations with unique transcriptional and functional profiles. These studies have highlighted alterations in immune cell subsets, stromal and epithelial cell signaling, and intercellular communication networks that collectively impair oocyte quality, embryo development, and endometrial receptivity in women with endometriosis. By dissecting the molecular signatures of individual cells, single-cell approaches provide insights into the mechanisms driving persistent inflammation, impaired angiogenesis, hormonal dysregulation, and immune dysfunction in endometriosis. Importantly, emerging evidence indicates that infertility and reduced assisted reproductive technology (ART) success in endometriosis reflect coordinated cellular and molecular dysfunction rather than solely anatomical abnormalities. Single-cell analyses of oocytes, granulosa cells, and endometrial cell populations demonstrate transcriptomic and epigenetic alterations affecting mitochondrial function, steroid metabolism, immune regulation, and implantation-related signaling pathways, offering a biological explanation for impaired implantation and variable ART outcomes. Integration of these findings with clinical observations supports the concept that endometriosis-associated reproductive failure arises from combined ovarian and endometrial defects detectable at the cellular level. Current single-cell studies highlight candidate biomarker signatures with the potential to improve patient stratification, predict ART outcomes, and guide individualized therapeutic strategies. As these discoveries are refined into clinically applicable biomarker panels, single-cell technologies are poised to bridge mechanistic understanding and precision reproductive medicine, enabling more personalized management approaches aimed at restoring reproductive competence in patients with endometriosis. Full article

The peri-implantation window is a tightly regulated temporal phase during which the human endometrium undergoes coordinated molecular remodeling to establish receptivity. MicroRNAs (miRNAs) contribute to implantation-related processes; however, whether dynamic endometrial regulatory signals are functionally reflected in circulation within a defined temporal framework remains unclear. We hypothesized that although individual miRNA identities differ between endometrial tissue and plasma, temporally regulated miRNAs in both compartments may exhibit overlap at the level of enriched biological pathways during the peri-implantation window. To test this hypothesis, we performed time-resolved small RNA sequencing on paired endometrial and plasma samples collected from 62 participants across progesterone exposure days P+3 to P+7 in hormonally controlled cycles. Temporal modeling identified 27 dynamic miRNAs in endometrial tissue and 17 in plasma (FDR < 0.05). Despite limited overlap at the individual miRNA level, functional enrichment analysis revealed recurrent overlap in apoptosis-, cell cycle-, aging-, inflammatory-, and metabolic-related pathways across compartments. Four miRNAs exhibited concordant directional temporal trends between tissue and plasma with moderate correlation coefficients. These findings suggest that dynamic miRNA-associated enrichment patterns during the peri-implantation window may exhibit pathway-level overlap despite divergence in specific molecular identities. This temporally aligned integrative framework provides a pathway-centric perspective for interpreting cross-compartment miRNA-associated temporal patterns and supports a hypothesis-generating systems-level view of human implantation biology. Full article

Multimorbidity is a key global trend across healthcare fields, including gynecology. It is strongly associated with an overall poorer health status. Statistics indicate that in the 21st century most women experience at least one gynecological disease. Meanwhile, there is a consistent increase in the prevalence of obesity associated with chronic inflammation and hyperestrogenism. Alongside other factors, it leads to a growing prevalence of hyperproliferative diseases of the female reproductive system (FRS), encompassing both benign and malignant conditions. While advanced-stage malignant tumors can be linked to missed detection and wrong checkup strategies, benign neoplasms can compromise the ovarian reserve and thus cause major concerns. The prevailing benign FRS tumors are uterine fibroids (UFs) and benign ovarian tumors (BOTs), including serous and mucinous cystadenomas. It appears that an increase in certain benign FRS tumors is occurring in parallel with a rise in infertility (especially “unexplained infertility”) and reproduction failures, potentially associated with endometrial dysfunction. Thus, the endometrium is currently considered a critical area of research due to its vital role as the site of blastocyst adhesion and implantation, especially in patients with comorbidities. In this context, this article highlights the significance and pathophysiological characteristics of UFs and BOTs and their impact on defective endometrial receptivity. Full article

Three-dimensional (3D) organoid and co-culture models have emerged as transformative tools for studying human endometrial function, implantation, and placental development, overcoming key limitations of animal and two-dimensional in vitro systems. This review synthesises available information of recent advances in endometrial epithelial organoids (EEOs), trophoblast organoids (TBOs), and increasingly complex co-culture platforms incorporating stromal, vascular, and trophoblast compartments to model epithelial–stromal crosstalk, decidualisation, angiogenesis, and embryo implantation. Emerging developments include assembloid systems, synthetic and semi-synthetic extracellular matrices, and microfluidic organ-on-a-chip technologies that enable long-term culture, hormonal responsiveness, and patient-specific modelling. These approaches have recapitulated key features of the mid-secretory endometrium, placental villous architecture, trophoblast differentiation, and early implantation events while revealing disease-associated dysfunctions in conditions such as endometriosis, adenomyosis, polycystic ovarian syndrome, and endometrial cancer. Despite significant progress, current models remain limited by incomplete cellular diversity, polarity constraints, and challenges in fully modelling immune and vascular interactions. Collectively, emerging 3D organoid and co-culture systems provide physiologically relevant platforms to interrogate human reproductive biology, elucidate mechanisms underlying implantation failure and placental disease, and support the development of personalised therapeutic strategies to improve reproductive outcomes. Full article

Infertility affects a substantial proportion of women of reproductive age and is frequently associated with impaired endometrial receptivity. Successful implantation depends on tightly regulated hormonal, immune, apoptotic, and stress-response pathways within the endometrium. This pilot study aimed to evaluate the expression and distribution of granulocyte colony-stimulating factor (G-CSF), bone morphogenetic proteins 2/4 (BMP-2/4), heat shock protein 70 (HSP-70), apoptosis, progesterone, estrogen, and pentraxin-3 (PTX-3) in the endometrium of infertile women across different menstrual cycle days. A descriptive cross-sectional analysis was performed on endometrial tissue samples obtained from six infertile women aged 21–49 years at various menstrual cycle days. Routine histology, immunohistochemistry, TUNEL assay, and chromogenic in situ hybridization were used to assess tissue morphology, protein expression, apoptotic activity, and PTX-3 gene expression. Quantitative evaluation was applied to immunohistochemical markers and apoptosis, while PTX-3 expression was assessed semi-quantitatively. G-CSF expression showed low-to-moderate levels with a relative mid-cycle increase. BMP-2/4 demonstrated the highest overall positivity across most cycle days, with marked inter-sample variability. HSP-70 exhibited pronounced cycle-dependent variability. Apoptotic activity increased toward mid-to-late cycle days. Progesterone and estrogen positivity was heterogeneous and limited to selected cycle days. PTX-3 gene expression was highest during mid-cycle days and decreased toward later phases. No clear association with patient age was observed. Conclusions: The findings indicate distinct and cycle-dependent patterns of immune, morphogenetic, apoptotic, hormonal, and inflammatory markers in the endometrium of infertile women. These results highlight the dynamic nature of endometrial regulation and suggest that altered temporal coordination of these pathways may contribute to impaired endometrial receptivity. Full article

Endometrial cancer (EC) is one of the most prevalent gynecological malignancies worldwide. Atypical endometrial hyperplasia (AEH) is a premalignant condition with a substantial risk of progression to EC, with the endometrioid subtype (EEC) being the most common. In this study, we investigated the escape-from-senescence concept as a model for the malignant progression from AEH to EEC by bioinformatic analysis of single-cell RNA sequencing data. Unciliated epithelial cells from AEH and EEC tissues exhibited significantly higher levels of senescence compared with those from normal endometrium. Both the proportion of senescent cells (SCs) and their senescence scores remained comparable between hyperplasia and cancer. Despite pronounced genomic instability, SCs in EEC showed no evidence of cell cycle re-entry. RNA velocity analysis revealed no transcriptional trajectories indicating a transition from senescent to non-senescent states in the EEC group. While SCs in AEH and EEC shared similar senescence-associated transcriptional profiles, they demonstrated differences in immunomodulatory activities with enhanced immunosuppressive signaling in the EEC group compared to AEH. Thus, we found no evidence supporting the occurrence of large-scale senescence escape and subsequent malignant conversion of epithelial SCs during EC development. Instead, senescence appears to represent a generalized stress response that persists throughout both premalignant and malignant stages. Full article

Background: The individual and social burden of endometriosis is high, and the diagnosis is usually delayed by 7–10 years. Menstrual effluent (ME) represents an accessible and uniquely informative biofluid. This systematic review evaluated the pathophysiological relevance and diagnostic potential of ME in endometriosis. Methods: Following PRISMA 2020 guidelines, we systematically searched PubMed/MEDLINE, EBSCOhost (Academic Search Premier, APA PsycArticles, APA PsycInfo, CINAHL, and MEDLINE), Semantic Scholar, and Google Scholar from inception to 30 November 2025. Original studies analyzing human ME or ME-derived cells in women with endometriosis versus controls were eligible. We extracted study design, analytic methods, diagnostic accuracy metrics (AUC, sensitivity, and specificity), mechanistic pathways, and risk of bias (QUADAS-2 for diagnostic, and NIH tools for mechanistic studies). Results: Thirty-five studies were included. ME consistently captured key pathophysiological mechanisms of endometriosis, including impaired decidualization and progesterone resistance, immune dysregulation with diminished cytotoxic clearance, pro-angiogenic and invasive phenotypes, heightened stem/progenitor cell survival, cellular senescence and DNA damage, and altered extracellular-vesicle signaling. Diagnostic accuracy was reported in nine studies. Aromatase mRNA showed the highest performance (AUC 0.977), followed by TGF-β1 (AUC 0.973) and IGFBP1 (AUC 0.92). A lipidomic two-marker model achieved an AUC of 0.87. All diagnostic assessments were based on case–control studies; none conducted prospective validation. Conclusions: ME is a biologically relevant, non-invasive, and patient-acceptable biospecimen reflecting core endometriosis mechanisms and yielding promising diagnostic accuracy. The highest diagnostic performance was achieved for assays reflecting steroidogenic and growth-factor pathways (e.g., aromatase and TGF-β1). Standardization and prospective validation are needed before clinical adoption. Full article

Is it reasonable to use allogeneic mesenchymal stem cells (MSCs) therapy for thin endometrium and recurrent implantation failure? Thin endometrium (TE) and recurrent implantation failure (RIF) are associated with poor reproductive outcomes. Single-cell RNA sequencing (scRNA-seq) shows that such pathologies involve functional impairment of endometrial stromal, vascular, immune cells rather than reductions in cell numbers. MSCs exert regenerative and immunomodulatory effects and are proposed as candidates for endometrial repair. scRNA-seq studies indicate that TE and RIF are characterized by stromal progenitor dysfunction, impaired angiogenesis, immune dysregulation, and cellular senescence, providing a biological rationale for investigating allogeneic MSC-based therapies. scRNA-seq studies of human endometrium in patients with TE and RIF are reviewed alongside experimental and clinical studies evaluating autologous and allogeneic MSCs, with particular emphasis on umbilical cord-derived MSCs. Transcriptomic analyses consistently demonstrate reduced proliferation and decidualization of endometrial stromal cells, suppression of angiogenesis, immune dysregulation, and activation of senescence-associated genes. Preclinical studies show that MSC administration restores endometrial structure, vascularization, and receptivity markers. Early clinical studies suggest potential benefit, although data remain limited and heterogeneous due to non-randomized studies. Allogeneic MSCs are promising as therapy, but further studies on mechanisms and clinical validation are needed. Full article

Background/Objectives: Pregnancy loss is a common and multifactorial complication of human reproduction, traditionally attributed to fetal chromosomal abnormalities, maternal anatomical and endocrine disorders, and immune dysfunction. Growing evidence now indicates that the maternal microbiome, particularly within the reproductive tract, plays a critical role in implantation, placental development, and the maintenance of immune tolerance during early pregnancy. Importantly, the influence of the microbiome on miscarriage appears to be strongly modulated by host genetic background and immune regulation. Methods: This narrative review summarizes current evidence linking alterations in the vaginal, endometrial, placental, and gut microbiomes to miscarriage, with a specific focus on host genetics and immune–microbial interactions. Results: We discuss how genetic variation in innate and adaptive immune pathways, inflammatory signaling, and mucosal barrier function may shape host responses to microbial communities, thereby influencing susceptibility to PL. In addition, we highlight emerging data on microbiome-driven regulation of gene expression and epigenetic modifications in the endometrium and decidua, emphasizing the role of microbial metabolites in immune tolerance and placental function. Conclusions: By integrating findings from microbiome research, host genomics, immunology, and epigenetics, this review proposes a framework in which miscarriage is viewed as a consequence of disrupted host–microbe crosstalk rather than isolated pathology. Finally, we address key methodological challenges and outline future research directions aimed at advancing mechanistic understanding and translational applications. Full article

Receptive endometrium (RE) is essential for mammalian embryo implantation. The establishment of RE is a complex and precise dynamic process regulated by various cytokines, including non-coding RNAs (miRNAs, lncRNAs, and circRNAs). We identified candidate miR-26b-3p and circRNA3890 from our previous endometrial non-coding RNA sequencing data. CircRNA3890 adsorbs miR-26b-3p and inhibits its activity. Mouse double minute 4 (MDM4) is a target gene of miR-26b-3p, and circRNA3890 up-regulates the expression level of MDM4 by inhibiting the activity of miR-26b-3p in dairy goat endometrial epithelial cells (gEECs) in vitro. circRNA3890/miR-26b-3p/MDM4 could promote the proliferation of gEECs through the p53 signaling pathway. MiR-26b-3p could regulate the expression levels of vascular endothelial growth factor A (VEGFA) and leukemia inhibitory factor (LIF) through MDM4 in gEECs, which contributes to the development of endometrial receptivity. Furthermore, the results showed that miR-26b-3p significantly promoted the development of RE and embryo implantation. These findings demonstrate that circRNA3890 targets and adsorbs miR-26b-3p to relieve MDM4 inhibition and promotes EEC proliferation through the p53 signaling pathway. They reveal the regulatory effect of miR-26b-3p on receptive endometrial development and embryo implantation in vitro and in vivo. Full article

Female reproductive tract (FRT) disorders such as maternal conditions and gynecological cancers represent a significant global health burden. However, women’s health, and particularly locally acting therapies targeting the FRT, has historically been underprioritized in drug development and translational research. Developing safe and effective therapies requires a clear understanding of drug transport across FRT barriers. Conventional in vitro culture systems and animal studies fail to recapitulate the physiological complexity of the human FRT, including stratified mucosal architecture, functional mucus barriers, microbiome interactions, as well as dynamic hormonal regulation. Recently, organ-on-chip (OoC) microfluidic platforms, integrating human cells with precisely controlled perfusion, have emerged as advanced in vitro systems capable of recreating dynamic physiological microenvironments. This review summarizes the major anatomical and physiological barriers of the FRT, including the vagina, cervix, endometrium, and placenta, and discusses critical design considerations for the development of FRT-on-chip models. We highlight the advanced OoC developed to study infection, drug permeation, hormonal responses, and maternal–fetal interface dynamics. Finally, future perspectives are outlined, including the integration of immune components, vascularization strategies, and multi-organ systems to better simulate inter-organ communication. Collectively, these advances underscore the potential of FRT-on-chip models as predictive platforms for preclinical drug screening, toxicity evaluation, and personalized medicine. Full article

The increasing antimicrobial resistance of T. pyogenes, one of the principal pathogens associated with endometritis, presents a formidable challenge in veterinary medicine. Astragaloside IV (AS-IV) is a triterpene saponin compound isolated from the traditional Chinese medicine Astragalus membranaceus. While recognized as the primary bioactive constituent of Astragalus membranaceus with diverse pharmacological properties, its potential to counteract T. pyogenes-induced endometritis has yet to be elucidated. In the current study, T. pyogenes infection models were successfully established in both mouse uteri and cultured goat endometrial epithelial cells (gEECs). Integrating histopathology, molecular biology and transcriptomic technology, this study characterized the multifaceted biological effects of AS-IV. Transcriptomic analysis indicates that the regulatory effects of AS-IV on T. pyogenes-induced infection are primarily associated with the enrichment of signaling pathways related to inflammation, apoptosis, and oxidative stress. Subsequent validation demonstrated that AS-IV treatment effectively alleviated T. pyogenes-induced endometrial damage by suppressing inflammation, apoptosis, and oxidative stress. These effects were mediated through Nrf2 and its downstream target HO-1, a mechanism further confirmed by the loss of protection upon Nrf2 inhibition. In summary, AS-IV protects the endometrium against T. pyogenes-induced inflammatory and oxidative damage by activating the Nrf2/HO-1 signaling pathway. Full article

Background: There is a need for intraoperative image guidance in gynecologic oncologic surgery to provide accurate identification of malignant tissue and ensure negative resection margins. Emerging imaging technologies can complement standard histopathology and reshape intraoperative decision-making. Spectral imaging can extract information on tissue composition and physiological status in real time, without the need for tissue contact, contrast agents, staining, or freezing. This systematic review synthesizes its current clinical applications in gynecologic oncology, decision support utility, and diagnostic performance with data processing frameworks for tissue classification. Materials and Methods: This systematic review (PROSPERO: CRD420251032899) adhered to PRISMA guidelines. PubMed, Google Scholar, Embase, ClinicalTrials.gov, and Scopus databases were searched until September 2025. Manuscripts reporting data on spectral imaging in gynecologic oncology were included in the analysis. Results: Twenty-nine studies and two clinical trials met the inclusion criteria. Most of them focused on cervical neoplasia (n = 17, 58.6%) and ovarian cancer (n = 7, 24.1%) detection, followed by assessment of the fallopian tubes (n = 2, 6.9%), endometrium (n = 1, 3.4%), and vulvar skin (n = 2, 6.9%). Using final pathology as the gold standard, overall specificity ranged from 30 to 99%, and overall sensitivity from 75 to 100%, with particularly high sensitivity for cervical lesions (79–100%) and ovarian cancer (81–100%). Among the included studies, thirteen (44.8%) used data interpretation algorithms, of which eleven (84.6%) applied machine learning, one (7.7%) deep learning, and one (7.7%) combined both. Conclusions: Spectral imaging, supported by computational methods, has shown promising results in the diagnostic evaluation of gynecologic disease by providing functional and molecular information beyond the capacities of standard visual assessment. Full article

Background/Objectives: The scientific community is still divided between supporters of the implantation theory and researchers who advocate the theory of coelomic metaplasia/embryonic cell remnants to explain the initiation of endometriosis. A frequently cited argument in favor of the coelomic metaplasia/embryonic cell remnants theory is the occurrence of endometriosis in the Mayer-Rokitansky-Kuster-Hauser syndrome, since retrograde menstruation is not possible without endometrium. However, nearly all women with uterovaginal agenesis have uterine remnants that harbour islets of endometrium. Methods: To verify the validity of the coelomic metaplasia/embryonic cell rests theory, we analysed all reports of endometriosis in patients with Mayer-Rokitansky-Kuster-Hauser syndrome without endometrium, published between 1980 and 2025. Three criteria had to be met in order to clearly demonstrate the absence of endometrium and the presence of endometriosis: (i) preoperative imaging, (ii) surgical visualization, and (iii) histological examination. Results: None of the nine reports fully met all three criteria, and the presence of endometrium could never be ruled out. In addition, we used ten characteristics to assess the ‘goodness’ of a theory: testability, logical coherence, conceptual clarity and comprehensibility, external consistency, empirical validity, predictive power, parsimony, broad applicability, practical utility, and heuristic value. Conclusions: Overall, the implantation theory appears to fully satisfy all criteria to explain the onset of endometriosis in Mayer-Rokitansky-Kuster-Hauser syndrome. In contrast, the coelomic metaplasia/embryonic cell rests theory satisfies eight criteria only partly and does not satisfy two of them. Therefore, the null hypothesis that endometriosis can be present in the absence of endometrium in patients with utero-vaginal agenesis can be reasonably rejected. Full article