Circulating endometrial cells (CECs) have emerged as a new biomarker of advanced disease in women with endometriosis. The identification of several subtypes of CECs (e.g., stem cell-like, epithelial, glandular, stromal) has opened the way for characterization of endometriosis-associated CECs. This study focused on the isolation and characterization of CECs and disseminated endometrial cells (DECs) in patients with spontaneous pneumothorax (SP). The primary objective was to differentiate between cancer and non-cancer cells in patients with no previous cancer diagnosis. The MetaCell® size-based separation protocol was used to enrich CECs/DECs. Evaluation of the captured cells by 3D microscopy was performed using a NANOLIVE™ microscope using a holographic approach. Based on gene expression analysis (GEA), we can conclude that mitochondria are much more active in primary tumors compared to endometriosis tissue (e.g. MT-ND1, MT-ATP6 genes). The culture of DECs is made of stromal, stem and immune cells. In vitro culture of DECs is characterized by an increase in the epithelial marker KRT18. Similarly, NFE2L2, a proerythroid factor, is also elevated. Further, a significant decrease in the amount of stem and immune cells was observed in the cell culture of DECs. The data presented here show how morphologically plastic the changes in the mitochondrial network can be and how cells can reflect them at the level of gene expression. The markers identified could help in the accompanying diagnostic process of the spontaneous pneumothorax in women of reproductive age.
- MeSH
- dospělí MeSH
- endometrióza * patologie diagnóza genetika MeSH
- endometrium patologie metabolismus MeSH
- lidé MeSH
- mitochondrie * metabolismus patologie MeSH
- pneumotorax * patologie diagnóza MeSH
- stanovení celkové genové exprese metody MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: Endometrial polyp (EP) is a type of pathology that is quite common in clinical practice. Although its exact etiology is not fully known, there is evidence to support that it is sensitive to hormonal stimuli. We aimed to investigate the relationship between kisspeptin (KP) and EP by comparing the genetic (tissue-blood) and immunohistochemical (IHC) expression of KP in EP lesions in patients with normal endometrial findings. MATERIALS AND METHODS: A prospective case-control study of 50 patients with EP (N = 25) and normal endometrial findings (N = 25) on biopsy and/or excision material was performed. Blood and biopsy samples obtained from all patients were stored at -80 °C. KP gene expression levels were determined from paraffin blocks, and peripheral venous blood samples obtained from biopsy specimens and IHC-H-score analysis were performed from paraffin blocks. EP and matched controls were compared for KP. RESULTS: After IHC, the KP H-score of the control group was higher than the EP group, and this difference was statistically significant; H-score: control: 5 (++; 1-15); polyp: 1 (+; 0-12) (P < 0.05). Although KP expression in both tissue and blood was higher in the control group than in the EP group, this difference was not statistically significant (P > 0.05). No significant correlation was found between IHC H-score and KP expression levels in tissue and blood. According to the ROC analysis, the tissue and blood KP expression cut-off value and area under the curve (AUC) predicting the likelihood of developing EP were not significant (tissue KP: 1.04, AUC: 0.570, P = 0.388, sensitivity 56%, specificity 60%, Blood KP: 1.06, AUC: 0.569, P = 0.401, sensitivity 80%, specificity 40%). CONCLUSIONS: Decreased KP expression level in EP lesions may predict the diagnosis of EP, and in the future, KP may have therapeutic potential for benign gynecological pathologies such as polyps.
- Klíčová slova
- endometrial polyps, endometrium, immunohistochemistry, kisspeptin, reverse-transcription PCR (RT-PCR),
- MeSH
- dospělí MeSH
- endometrium metabolismus patologie MeSH
- imunohistochemie * MeSH
- kisspeptiny * genetika metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- nemoci dělohy genetika metabolismus patologie krev MeSH
- polypy * genetika metabolismus patologie MeSH
- prospektivní studie MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- kisspeptiny * MeSH
During pregnancy, two fetomaternal interfaces, the placenta-decidua basalis and the fetal membrane-decidua parietals, allow for fetal growth and maturation and fetal-maternal crosstalk, and protect the fetus from infectious and inflammatory signaling that could lead to adverse pregnancy outcomes. While the placenta has been studied extensively, the fetal membranes have been understudied, even though they play critical roles in pregnancy maintenance and the initiation of term or preterm parturition. Fetal membrane dysfunction has been associated with spontaneous preterm birth (PTB, < 37 weeks gestation) and preterm prelabor rupture of the membranes (PPROM), which is a disease of the fetal membranes. However, it is unknown how the individual layers of the fetal membrane decidual interface (the amnion epithelium [AEC], the amnion mesenchyme [AMC], the chorion [CTC], and the decidua [DEC]) contribute to these pregnancy outcomes. In this study, we used a single-cell transcriptomics approach to unravel the transcriptomics network at spatial levels to discern the contributions of each layer of the fetal membranes and the adjoining maternal decidua during the following conditions: scheduled caesarian section (term not in labor [TNIL]; n = 4), vaginal term in labor (TIL; n = 3), preterm labor with and without rupture of membranes (PPROM; n = 3; and PTB; n = 3). The data included 18,815 genes from 13 patients (including TIL, PTB, PPROM, and TNIL) expressed across the four layers. After quality control, there were 11,921 genes and 44 samples. The data were processed by two pipelines: one by hierarchical clustering the combined cases and the other to evaluate heterogeneity within the cases. Our visual analytical approach revealed spatially recognized differentially expressed genes that aligned with four gene clusters. Cluster 1 genes were present predominantly in DECs and Cluster 3 centered around CTC genes in all labor phenotypes. Cluster 2 genes were predominantly found in AECs in PPROM and PTB, while Cluster 4 contained AMC and CTC genes identified in term labor cases. We identified the top 10 differentially expressed genes and their connected pathways (kinase activation, NF-κB, inflammation, cytoskeletal remodeling, and hormone regulation) per cluster in each tissue layer. An in-depth understanding of the involvement of each system and cell layer may help provide targeted and tailored interventions to reduce the risk of PTB.
- MeSH
- amnion metabolismus cytologie MeSH
- chorion metabolismus MeSH
- decidua * metabolismus MeSH
- dospělí MeSH
- extraembryonální obaly * metabolismus MeSH
- lidé MeSH
- porod v termínu genetika MeSH
- předčasný odtok plodové vody genetika metabolismus MeSH
- předčasný porod * genetika MeSH
- stanovení celkové genové exprese MeSH
- těhotenství MeSH
- transkriptom * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
This article presents a comprehensive review of factors that increase the risk of malignancy in ultrasound findings of an endometrial polyp. We collected original studies, reviews, and meta-analyses that dealt with the topic of endometrial polyps and the risk of developing endometrial cancer. Each presumed risk factor was analysed individually. According to searched studies, abnormal uterine bleeding, old age, and body mass index are valid risk factors for developing endometrial cancer in endometrial polyps. Lynch syndrome patients are also in a high-risk group for endometrial cancer. On the other hand, the number of polyps, their size, diabetes mellitus, hypertension, and positive family history are factors with inconclusive results. There are either not enough data or different results among several studies.
- Klíčová slova
- Endometrial carcinoma, abnormal uterine bleeding, doppler ultrasound of uterine artery, endometrial cancer, endometrial polyp, polyp size, risk factors, tamoxifen,
- MeSH
- děložní krvácení etiologie MeSH
- endometrium patologie MeSH
- hysteroskopie MeSH
- lidé MeSH
- nádory dělohy * patologie MeSH
- nádory endometria * diagnostické zobrazování etiologie MeSH
- nemoci dělohy * komplikace MeSH
- polypy * diagnostické zobrazování patologie MeSH
- rizikové faktory MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
AIM: The effect of platelet-rich autoplasma on endometrial thickness and receptor sensitivity to estrogen and progesterone. MATERIALS AND METHODS: This prospective clinical study included 200 patients. The participants in the study were divided into two groups. The first control group received hormone replacement therapy (HRT). The second study group received an intrauterine infusion of platelet-rich autoplasma (PRP group). On the 19th day of the menstrual cycle, an ultrasound examination was performed to assess endometrial thickness, as well as an immunohistochemical analysis to determine receptor sensitivity to estrogen and progesterone. RESULTS: In the course of the study, we found that the use of platelet-rich autoplasma increased the thickness of the endometrium by 0.85 mm; the average thickness of the endometrium in the group who received PRP therapy was 8.25 (8.25-8.61) mm; and in the group of patients who only received HRT, it was 7.40 (7.34-7.65) mm. The sensitivity of receptors to estrogen in the experimental group increased by 3.5, in the experimental group it was 75.00 (71.43-74.22), and in the control group it was 71.50 (67.05-70.85). The sensitivity of receptors to progesterone also increased by 9.0, in the experimental group it was 95.0 (91.4-93.8), and in the control group it was 86.0 (83.47-86.27). CONCLUSION: Due to the action of platelet factors, PRP therapy has a positive effect on the endometrium, increasing its thickness and improving its receptivity. Therefore, it can be concluded that this method can find great practical application to improve the outcomes of assisted reproductive technology programs.
- Klíčová slova
- infertility, platelet-rich autoplasma, thin endometrium,
- MeSH
- dospělí MeSH
- endometrium * diagnostické zobrazování metabolismus účinky léků MeSH
- estrogeny MeSH
- lidé MeSH
- plazma bohatá na destičky MeSH
- progesteron * MeSH
- prospektivní studie MeSH
- receptory pro estrogeny metabolismus MeSH
- receptory progesteronu metabolismus MeSH
- trombocyty metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- estrogeny MeSH
- progesteron * MeSH
- receptory pro estrogeny MeSH
- receptory progesteronu MeSH
Reproductive immunology is at the forefront of research interests, aiming to better understand the mechanisms of immune regulation during gestation. The relationship between the immune system and the implanting embryo is profound because the embryo is semi-allogenic but not targeted by the maternal immune system, as expected in graft-versus-host reactions. The most prominent cell population at the maternal-fetal interface is the population of uterine natural killer (uNK) cells. Uterine NK cells are two-faced immunologically active cells, bearing comparison with Janus, the ancient Roman god of beginnings and endings. Their first face can be seen as natural killer cells, namely lymphocytes, which are critical for host defense against viruses and tumors. Even though uNK cells contain cytolytic molecules, their cytotoxic effect is not applied to classical target cells in vivo, playing a permissive rather than a defensive role. Their second face is crucial in maintaining physiological gestation-uNK cells show critical immunomodulatory functions with the potential to control embryo implantation and trophoblast invasion, regulate placental vascular remodeling, and promote embryonic/fetal growth. Therefore, we believe that their current designation "natural killer cells" (the first "cytotoxic" Janus's face) is misleading and inappropriate, considering their principal function is supporting and maintaining pregnancy. In this narrative review, we will focus on three lesser-known areas of knowledge about uNK cells. First, from the point of view of histology, we will comprehensively map the history of the discovery of these cells, as well as the current histological possibilities of their identification within the endometrium. To be brief, the discovery of uNK cells is generally attributed to Herwig Hamperl, one of the most influential and prominent representatives of German pathology in the 20th century, and his co-worker, Gisela Hellweg. Secondly, we will discuss the interesting aspect of terminology, since uNK cells are probably one of the human cells with the highest number of synonymous names, leading to significant discrepancies in their descriptions in scientific literature. From the first description of this cell type, they were referred to as endometrial granulocytes, granular endometrial stromal cells, or large granular lymphocytes until the end of the 1980s and the beginning of the 1990s of the last century, when the first publications appeared where the name "uterine NK cells" was used. The third area of present review is medical teaching of histology and clinical embryology. We can confirm that uNK cells are, in most textbooks, overlooked and almost forgotten cells despite their enormous importance. In the present narrative review, we summarize the lesser-known historical and terminological facts about uNK cells. We can state that within the textbooks of histology and embryology, this important cell population is still "overlooked and neglected" and is not given the same importance as in fields of clinical research and clinical practice.
- Klíčová slova
- Hamperl cells, Terminologia Histologica, endometrium, histology, immunohistochemistry, medical education, uterine NK cells,
- MeSH
- buňky NK MeSH
- endometrium MeSH
- lidé MeSH
- placenta * MeSH
- studium lékařství * MeSH
- těhotenství MeSH
- uterus MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The majority of endometrial and cervical cancers present with abnormal vaginal bleeding but only a small proportion of women suffering from vaginal bleeding actually have such a cancer. A simple, operator-independent and accurate test to correctly identify women presenting with abnormal bleeding as a consequence of endometrial or cervical cancer is urgently required. We have recently developed and validated the WID-qEC test, which assesses DNA methylation of ZSCAN12 and GYPC via real-time PCR, to triage women with symptoms suggestive of endometrial cancer using ThinPrep-based liquid cytology samples. Here, we investigated whether the WID-qEC test can additionally identify women with cervical cancer. Moreover, we evaluate the test's applicability in a SurePath-based hospital-cohort by comparing its ability to detect endometrial and cervical cancer to cytology. In a set of 23 cervical cancer cases and 28 matched controls the receiver operating characteristic (ROC) area under the curve (AUC) is 0.99 (95% confidence interval [CI]: 0.97-1.00) with a sensitivity and specificity of 100% and 92.9%, respectively. Amongst the hospital-cohort (n = 330), the ROC AUC is 0.99 (95% CI: 0.98-1) with a sensitivity and specificity of 100% and 82.5% for the WID-qEC test, respectively, and 33.3% and 96.9% for cytology (considering PAP IV/V as positive). Our data suggest that the WID-qEC test detects both endometrial and cervical cancer with high accuracy.
- Klíčová slova
- DNA methylation, abnormal vaginal bleeding, cervical cancer, early detection, endometrial cancer,
- MeSH
- cytodiagnostika MeSH
- děložní krvácení diagnóza patologie MeSH
- dysplazie děložního hrdla * diagnóza MeSH
- endometrium patologie MeSH
- infekce papilomavirem * diagnóza MeSH
- lidé MeSH
- nádory děložního čípku * diagnóza genetika patologie MeSH
- senzitivita a specificita MeSH
- studie proveditelnosti MeSH
- vaginální stěr MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Endometrial carcinoma (ECa) is one of the most common neoplasia of the female genital tract. The phosphatase and tensin (PTEN) homolog is the most frequently mutated tumor suppressor gene in endometrial carcinoma. PTEN encodes a phosphatase, a key regulatory enzyme involved in a signal transduction pathway that regulates cell growth, migration and apoptosis. The study evaluates an association between the morphological appearance of endometrial hyperplasia and ECa, and the presence of PTEN variations, PTEN protein´s level and intracellular localization. A total of 67 archived formalin-fixed and paraffin-embedded human biopsy tissue specimens with normal proliferative and secretory endometrium, endometrial hyperplasia without atypia and endometrial atypical hyperplasia, endometrioid the grade G1 and G3 and serous subtype of ECa were evaluated by sequencing for the presence of mutations in coding regions of PTEN gene of endometrial epithelial cells. The PTEN gene expression and intercellular localization of PTEN protein were evaluated immunohistochemically by immunoreactive score (IRS). PTEN mutation spectrum in endometrial carcinoma was identified for Slovak population. 28 non-silent mutations were identified in PTEN, twelve of them were novel, not annotated in Catalogue of Somatic Mutations in Cancer. Higher frequency of PTEN mutations was observed in serous carcinoma compared to global average. No correlation was observed between samples´ IRS, PTEN cellular localization and identified mutations. PTEN sequencing can be beneficial for patients considering prognosis of disease and sensitivity to treatment.
- MeSH
- endometrium metabolismus patologie MeSH
- fosfohydroláza PTEN genetika MeSH
- hyperplazie endometria * genetika patologie MeSH
- lidé MeSH
- mutace MeSH
- nádory endometria * diagnóza genetika MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Slovenská republika epidemiologie MeSH
- Názvy látek
- fosfohydroláza PTEN MeSH
- PTEN protein, human MeSH Prohlížeč
Despite recent advancements in reproductive medicine, recurrent implantation failure and habitual abortion remain ongoing issues. One of the most important aspects of successful implantation is the intricate immune response and regulation necessary for the acceptance of the hemiallogenic embryo. The most numerous immune cells in the decidua are uterine natural killer cells (uNK). Studies suggest that changes in the uNK count and physiology may be responsible for the aforementioned pathological conditions. Thus, testing for uNK may provide valuable insights into their pathogenesis. The study compared Pipelle endometrial sampling with conventional curettage to find out whether the less invasive Pipelle method is a viable alternative of tissue collection. Tissue samples from 14 patients obtained by both methods were examined. The average size of tissue samples obtained with Pipelle was 17 mm2, samples obtained with curettage had on average 34 mm2. Using immunohistochemical visualization of CD56 (NK cells) and granzyme B antigens (serine protease-expressing activation state of NK cells), it was found that the average total count of CD56 / mm2 was for Pipelle 115 and 120 for curettage, respectively. The study also proved a correlation between granzyme B positivity and identification of NK cells clusters. The results indicated that Pipelle endometrial sampling seems a suitable method of tissue harvesting for the purpose of uNK cells examination. Pipelle endometrial sampling is safe, cost-effective and can be performed on an outpatient basis without the need of anesthesia or analgesia. Several issues remain yet to be solved: how to standardize the subsequent uNK testing, how to interpret the results and finally yet importantly, how to use this knowledge in personalized treatment protocols.
- MeSH
- buňky NK MeSH
- endometrium * patologie MeSH
- granzymy MeSH
- habituální potrat * diagnóza patologie MeSH
- lidé MeSH
- těhotenství MeSH
- uterus patologie MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- granzymy MeSH
OBJECTIVE: A summary of new knowledge on embryo implantation in dependence on quality of the endometrium. METHODS: Literature review from August 2022 of the relevant publications in Web of Science, Scopus and PubMed/Medline databases, focused on “endometrial receptivity”, “polycystic ovary syndrome”, “endometriosis”, “SARS-CoV-2”. RESULTS: The receptive state of the endometrium is a result of physiological remodeling and immune system activity modulated by the microbio-me. This balance can be disturbed by myomas, polyps, sactosalpings, adenomyosis, endometriosis, polycystic ovary syndrome, infections. The effect of SARS-CoV-2 infection is being discussed. For a successful implantation, timing of transfer is crucial. The ultrasound examination is used conventionally. In specific cases, hysteroscopy and endometrium bio-psy are recommended. Histological and immunohistochemical evaluation is performed together with examination of microbio-me or transcriptome. To support the implantation, gestagenes are used, or metformin in the patients with polycystic ovary syndrome. In cases of a repeated implantation failure, the intrauterine infusion of mononuclear cells or platelet rich plasma is used, subcutaneous application of granulocyte colony stimulating growth factor, intravenous application of atosiban or intrauterine application of human chorionic gonadotropin. CONCLUSION: Recent research in the field of transcriptomics, proteomics and reproductive immunology uncovers the process of implantation more deeply and opens a new stage of the assisted reproduction.
- Klíčová slova
- Endometriosis, SARS-CoV-2, adenomyosis, endometrial receptivity, implantation, polycystic ovaries, proteome, receptivity of endometrium, secretome,
- MeSH
- choriogonadotropin MeSH
- COVID-19 * metabolismus MeSH
- endometrióza * MeSH
- endometrium fyziologie MeSH
- implantace embrya fyziologie MeSH
- lidé MeSH
- SARS-CoV-2 MeSH
- syndrom polycystických ovarií * MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- choriogonadotropin MeSH