Pathogenesis Of Endometrial Polyps Research Articles

Endometrial microbiota alteration in female patients with endometrial polyps based on 16S rRNA gene sequencing analysis.

The potential role of the endometrial microbiota in the pathogenesis of endometrial polyps (EPs) warrants further investigation, given the current landscape of limited and inconclusive research findings. We aimed to explore the microecological characteristics of the uterine cavity in patients with EPs and investigate the potential of endometrial microbiota species as novel biomarkers for identifying EPs. Endometrial samples were collected from 225 patients who underwent hysteroscopies, of whom 167 had EPs, whereas 58 had non- hyperproliferative endometrium status. The endometrial microbiota was assessed using 16S rRNA gene sequencing. We characterized the endometrial microbiota and identified microbial biomarkers for predicting EPs. The endometrial microbial diversity and composition were significantly different between the EP and control groups. Predictive functional analyses of the endometrial microbiota demonstrated significant alterations in pathways involved in sphingolipid metabolism, steroid hormone biosynthesis, and apoptosis between the two groups. Moreover, a classification model based on endometrial microbial ASV-based biomarkers along with the presence of abnormal uterine bleeding symptoms achieved powerful classification potential in identifying EPs in both the discovery and validation cohorts. Our study indicates a potential association between altered endometrial microbiota and EPs. Endometrial microbiota-based biomarkers may prove valuable for the diagnosis of EPs. Chinese Clinical Trial Registry (ChiCTR2100052746).

Mendelian randomization analysis of the association between human blood cell traits and uterine polyps

Human blood cells (HBCs) play essential roles in multiple biological processes but their roles in development of uterine polyps are unknown. Here we implemented a Mendelian randomization (MR) analysis to investigate the effects of 36 HBC traits on endometrial polyps (EPs) and cervical polyps (CPs). The random-effect inverse-variance weighted method was adopted as standard MR analysis and three additional MR methods (MR-Egger, weighted median, and MR-PRESSO) were used for sensitivity analyses. Genetic instruments of HBC traits was extracted from a large genome-wide association study of 173,480 individuals, while data for EPs and CPs were obtained from the UK Biobank. All samples were Europeans. Using genetic variants as instrumental variables, our study found that both eosinophil count (OR 0.85, 95% CI 0.79–0.93, P = 1.06 × 10−4) and eosinophil percentage of white cells (OR 0.84, 95% CI 0.77–0.91, P = 2.43 × 10−5) were associated with decreased risk of EPs. The results were robust in sensitivity analyses and no evidences of horizontal pleiotropy were observed. While we found no significant associations between HBC traits and CPs. Our findings suggested eosinophils might play important roles in the pathogenesis of EPs. Besides, out study provided novel insight into detecting uterine polyps biomarkers using genetic epidemiology approaches.

Expression of ID2 and Cyclooxygenase 2 Genes in Endometrial Tissues and Their Clinical Significance in the Pathogenesis of Endometrial Polyps

To investigate the expression of Deoxyribonucleic acid binding inhibitor 2 and Cyclooxygenase 2 genes in endometrial polyps patient’s endometrial tissues and analyze their clinical significance is the main objective. 38 patients with endometrial polyps who were treated at the minimally invasive gynecologic and reproductive surgery department of our hospital from October 2020 to December 2020 were selected as the test group, and their polyps and the endometrial tissue around the polyps were taken. 36 cases of women who had undergone intrauterine device placement surgery at the same time were scraped from the endometrium before intrauterine device placement. The messenger ribonucleic acid expression and protein levels of deoxyribonucleic acid binding inhibitor 2 and cyclooxygenase 2 in endometrial tissues were detected by quantitative reverse transcription polymerase chain reaction and western blot. In addition, enzymelinked immunosorbent assay was used to detect the levels of vascular endothelial growth factor, tumor necrosis factor-alpha, interleukin 1 beta and cancer antigen 125 and to analyze their relationship with the expression of Deoxyribonucleic acid binding inhibitor 2 and cyclooxygenase 2 in endometrial tissues of endometrial polyp’s patients. The results showed that the expression of Deoxyribonucleic acid binding inhibitor 2 and cyclooxygenase 2 messenger ribonucleic acid and protein levels in endometrial tissues were significantly higher in the experimental group compared with the control group, and the difference was statistically significant. Deoxyribonucleic acid binding inhibitor 2 was positively correlated with vascular endothelial growth factor, tumor necrosis factor alpha, interleukin 1 beta and cancer antigen 125 (p<0.05), while cyclooxygenase 2 was positively correlated with interleukin 1 beta and cancer antigen 125 in the endometrial tissues of patients in the test group. The sensitivity of Deoxyribonucleic acid binding inhibitor 2 was 87.32 %, specificity was 64.88 % and cut-off value was 1.68; the sensitivity of cyclooxygenase 2 was 93.15 %, specificity was 84.33 % and cut-off value was 2.03. Deoxyribonucleic acid binding inhibitor 2 and cyclooxygenase 2 in endometrial tissues has a high predictive value for the clinical diagnosis of endometrial polyps. Expression is closely related to the development of endometrial polyps, and both may be candidate specific target genes for endometrial polyps, and both may be used as markers for the clinical diagnosis of endometrial polyps.

ENDOMETRIAL POLYPS. QUESTIONS OF ETIOLOGY AND PATHOGENESIS

Endometrial polyps are a fairly common type of pathological endometrial hyperplastic process, but the molecular and pathogenetic mechanism underlying their formation and progression remains unclear. However, today their development is explained by a change in the level of normally hormonal reception and secretion of women more often in the premenopausal period or a dysregulation of mitotic activity in endometrial cells. The aim of our study is to study the etiology and pathogenesis of endometrial polyps among women of different age groups using general scientific and morphological research methods. According to histological studies of biopsy samples (scrapings) from the uterine cavity, taken from the archive of the pathological anatomical department of the 442nd military district hospital named after Z.P. Soloviev for the period 2017-2019, revealed pathomorphological features of endometrial polyps among women of different age groups with metrorrhagia and associated pathologies: uterine fibroids, cervical canal polyps (of the same etiology), adenomyosis, infertility. More often, endometrial polyps are combined with uterine myoma (54%) and adenomyosis (43%), which emphasizes the similarity of premorbid background, the same clinical manifestations of diseases and their clinical and pathological features. The main factor in the development of endometrial polyps among women of reproductive age and the premenopausal period in age is a change in hormonal levels, namely, an increase in the secretion and reception of estrogen and a decrease in the reception and secretion of progesterone. And among postmenopausal women undergoing hormonal and antitumor therapy against the background of endometrial atrophy, the formation of endometrial polyps is associated with a change in the regulation of mitotic activity in endometrial cells, which is detected by the expression of Ki-67 protein.

Serum concentrations of heavy metals in women with endometrial polyps

Endometrial polyps are one of the common reasons of abnormal uterine bleeding in women. Industrialisation, urbanisation and increased air pollution cause increased heavy metal exposure. Heavy metals that have oestrogenic effects in human body are named as metalloestrogens. The aim of this study was to investigate the serum metalloestrogen levels such as copper (Cu), zinc (Zn), aluminium (Al), lead (Pb), nickel (Ni) and Cu/Zn ratio and their possible relationship with the occurrence of endometrial polyps. Eighty women with abnormal uterine bleeding were divided into two groups: 40 women diagnosed with endometrial polyp (study group) and 40 women without endometrial polyp (control group). Ages, body mass indices, smoking behaviours, drinking water choices, chronic diseases and intrauterine device histories were noted for all patients. Blood levels of Cu, Zn, Al, Pb, Ni and Cu/Zn ratio were analysed by inductively coupled plasma-mass spectrometry method for both groups. No statistically significant differences were observed in terms of serum median levels of Cu and Pb between the study and the control groups. The serum median levels of Zn, Ni and Al were found to be statistically lower in the study group when compared with the control group. The Cu/Zn ratio was statistically higher in the study group. High Cu/Zn ratio, as a biomarker of oxidative stress, suggests the role of oxidative stress in etiopathogenesis of endometrial polyps.IMPACT STATEMENTWhat is already known on this subject? Studies demonstrate that oestrogen and progesterone play an important role in pathogenesis of endometrial polyps. Inorganic heavy metal ions that bind and activate oestrogen receptors are referred to as ‘metalloestrogens’. Apart from toxic effects, metalloestrogens have been linked to the aetiology of oestrogen-dependent diseases such as breast and endometrium cancer and endometriosis. However, serum levels of heavy metals were not investigated in a large group of endometrial polyp patients.What do the results of this study add? This is the first study investigating the serum levels of heavy metals in a large group of endometrial polyp patients. We did not observe any increased serum levels of heavy metals in endometrial polyp patients. Our results might suggest that oestrogenic heavy metal exposure has no role in the appearance of endometrial polyps. However, increased Cu/Zn ratio due to low serum levels zinc suggests oxidative stress might play a role in endometrial polyps.What are the implications of these findings for clinical practice and/or further research? Further research of heavy metals in endometrial polyps with simultaneous blood and tissue samples could show the precise effect of environmental exposure of metalloestrogens in aetiopathogenesis of endometrial polyps.

Decreased ADAMTS-1, -9 and -20 levels in women with endometrial polyps: a possible link between extracellular matrix proteases and endometrial pathologies

A disintegrin-like and metalloproteinase domain with thrombospondin-type 1 motifs (ADAMTS) protein superfamily includes 19 secreted metalloproteases. Proteolytic substrates of ADAMTS enzymes have been linked to female reproductive function. Herein, we aimed to investigate serum ADAMTS-1, -9 and -20 levels in women with and without endometrial polyps (EPs). The study group (n = 40) consisted of women who had hysteroscopically detected and histologically confirmed EPs whereas control group (n = 40) was recruited from those women without any endometrial pathology. Data recorded for every woman were as follows: age, body mass index, gravidity and parity, number of miscarriages, smoking status and serum ADAMTS-1, -9 and -20 levels. ADAMTS-1, -9 and -20 values were measured by commercially available ELISA kits. No statistically significant differences between the groups were observed in terms of demographics. There were also no statistically significant differences between the groups with regard to ADAMTS-1 and -20 levels, although both of them were lower in the study group. However, ADAMTS-9 was significantly lower in the study group compared to the controls (p = .010). The optimal cut off value of ADAMTS-9 in predicting EPs was found to be 163.2 ng/mL with 100% sensitivity and 35% specificity. In conclusion, ADAMTS-9 protein is decreased in women with EPs.Impact statementWhat is already known on this subject? Endometrial polyps (EPs) are common and are generally benign gynaecologic disorders. ADAMTS enzymes comprise a zinc metalloproteinase gene family that has roles in vascular biology, inflammation and especially in the control of the function and structure of the extracellular matrix (ECM). ECM plays an important role in the pathogenesis of myomas, adenomyosis and abnormal uterine bleeding, as well as EPs. There is an interest in these proteases, especially with regard to the physiology of ovulation and implantation. They are also associated with carcinogenesis and metastasis. One of the most feared consequences of EPs is the risk of malignancy. Therefore, it is important in gynaecology practice to diagnose these endometrial abnormalities.What do the results of this study add? This is the first study performed to investigate the relationship between some ADAMTS (-1, -9 and -20) proteases and uterine polyps. Our results demonstrate novel molecular mediators contributing to EPs physiopathology.What are the implications of these findings for clinical practice and/or further research? ADAMTS-9 is defined as a tumour suppressor gene in various malignancies. Decreased ADAMTS-9 protein, which is the product of this gene, may have a role in the pathogenesis of EPs. There is a need for further research that should be done with benign–malign EPs.

Endometrial Polyps and Benign Endometrial Hyperplasia Have Increased Prevalence of DNA Fragmentation Factors 40 and 45 (DFF40 and DFF45) Together With the Antiapoptotic B-Cell Lymphoma (Bcl-2) Protein Compared With Normal Human Endometria.

DNA fragmentation factor 40 (DFF40) is a key executor of apoptosis. It localizes to the nucleus together with DNA fragmentation factor 45 (DFF45), which acts as a DFF40 inhibitor and chaperone. B-cell lymphoma (Bcl-2) protein is a proven antiapoptotic factor present in the cytoplasm. In this study, we aimed to investigate DFF40, DFF45, and Bcl-2 immunoexpression in endometrial polyps (EPs) and benign endometrial hyperplasia (BEH) tissue compared with that in normal proliferative endometrium (NPE) and normal secretory endometrium (NSE) as well as normal post menopausal endometrium (NAE). This study used archived samples from 65 and 62 cases of EPs and BEH, respectively. The control group consisted of 52 NPE, 54 NSE, and 54 NAE specimens. Immunohistochemistry was used to detect DFF40, DFF45, and Bcl-2. DFF40, DFF45, and Bcl-2 were more highly expressed in the glandular layer of EPs and BEH compared with the stroma, and this was not influenced by menopausal status. Both glandular and stromal expression of DFF40, DFF45, and Bcl-2 were significantly higher in EPs compared with NPE, NSE, and NAE. Glandular BEH tissue showed significantly higher DFF40, DFF45, and Bcl-2 expression than in NPE, NSE, and NAE. No differences in the glandular expression of DFF40, DFF45, and Bcl-2 were observed between EP and BEH tissues, while Bcl-2 stromal expression in BEH was significantly lower than in EPs. Glandular, menopause-independent DFF40, DFF45, and Bcl-2 overexpression may play an important role in the pathogenesis of EPs and BEH.

Survivin Expression in Simple Endometrial Polyps and Tamoxifen-associated Endometrial Polyps

Endometrial polyps are benign pathologies originating as localized overgrowths of basal endometrium. Risk factors include endogenous and exogenous estrogen excess and tamoxifen (TAM) exposure. Our main objective was to investigate the role of an apoptosis-inhibiting protein, survivin, in endometrial polyps. We performed a cross-sectional, analytical study; our samples were obtained from the archives of the Department of Pathology. Sixty samples were included, comprising 20 TAM polyps, 20 simple endometrial polyps, and 20 cases of simple endometrial hyperplasia without atypia not associated with TAM use. Immunohistochemical staining with rabbit monoclonal anti-human survivin, clone EP 119, was performed. Survivin staining score was highest in the endometrial polyp group and lowest in the TAM polyp group (P<0.001). There was no correlation between survivin staining score and the age of patient (r=0.09), TAM exposure (r=-0.02), nor endometrial thickness (r=0.25). Endometrial polyps are frequently associated with TAM. The low expression of the antiapoptotic marker survivin in TAM polyps but high expression in other polypoid endometrium illustrates that different mechanisms are responsible in the pathogenesis of endometrial polyps. It is possible that there is a direct effect of TAM on apoptosis or indirect effect through a progesterone-related mechanism.

Investigation of the Roles of Cyclooxygenase-2 and Galectin-3 Expression in the Pathogenesis of Premenopausal Endometrial Polyps.

Background:The pathogenesis and etiology of endometrial polyps has not been elucidated. In this study, we aimed to examine the pathogenic mechanisms of endometrial polyp development using immunohistochemistry. We evaluated the expression of galectin-3 and cyclooxgenase-2 (COX-2) during the menstrual cycle in premenopausal women with endometrial polyps or normal endometrium.MethodsThirty-one patients with endometrial polyps and 50 healthy control patients were included in this study. The levels of expression of COX-2 and galectin-3 were studied by immunohistochemistry.Results:The percentage of COX-2–positive cells and the intensity of COX-2 staining in the endometrium did not vary during the menstrual cycle either in the control group or in patients with endometrial polyps. However, expression of galectin-3 was significantly lower in endometrial polyps and during the proliferative phase of the endometrium compared with the secretory phase.Conclusions:Our data suggests that the pathogenesis of endometrial polyps does not involve expression of COX-2 or galectin-3.

Uterine Cavity Assessment and Endometrial Hormonal Receptors in Women with Peri and Post Menopausal Bleeding

Objectives: To compare the accuracy of 2D-Transvagfinal ultrasound (TVUS), saline infused sonohysterography (SIS) and hysteroscopy (DH) in assessment of the uterine cavity in women with peri- and postmenopausal bleeding and to study the expression of endometrial estrogen receptors (ER) and progesterone receptors (PR) in them. Study design: 100 women with abnormal uterine bleeding (peri and postmenopausal) were subjected to TVUS, SIS and DH and fractional curettage followed by histopathological examination and immunohistochemical analysis for ER and PR. Results: Measurement of endometrial thickness by TVUS showed a significant difference between normal and atrophic endometrium and between atrophic endometrium and endometrial polyp (P value 0.004 and 0.001 respectively) DH had the best sensitivity, specificity, PPV and NPV as a diagnostic procedure followed by SIS then TVUS (97.7, 100,100,99.4 % vs. 74,91.2,67.3,93.5 and 52.9,89.4,56.3, 88.1 respectively) Both ER and PR scoring among glands and stroma showed a significant difference between normal and abnormal endometrium. ER expression in glands showed a significant difference between endometrial polyp and surrounding endometrium (P value 0.006) Conclusions: Sonohysterography is superior to ultrasound and very close to hysteroscopy, especially with intra-cavitary lesions. Hysteroscopy remains the gold standard for uterine cavity assessment, but cannot replace the histopathology. The expression of endometrial steroid receptors is important in the pathogenesis of endometrial polyps and endometrial hyperplasia.

Steroid Hormone Receptor Profile of Premenopausal Endometrial Polyps

The etiology and pathogenesis of endometrial polyps (EPs) are only partially understood. To better understand how sex steroids regulate polyp growth, we investigated the messenger RNA (mRNA) expression of the genes of reproductive steroid hormone receptors (estrogen receptors alpha [ERalpha] and beta [ERbeta], G protein-coupled receptor 30 [GPR30], and progesterone receptor [PR]) in EP tissue and autologous normal appearing endometrium (R) Within each patient, the normal appearing endometrial tissue remote from the site of the endometrial polyp (R) was taken as an internal control. Relative expressions of genes of interest within the endometrial polyp were compared to expressions of respective genes within the internal control tissue (i.e. R). R is the abbreviation for normal appearing endometrium in the later calculation formula. Ten patients diagnosed with EP in a tertiary care center were included in this study. Directed biopsies were obtained under hysteroscopy from the EP and from a normal appearing site remote from EP along the opposite uterine wall in each patient. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) was used for gene expression profiling in the paired tissue samples. The relative gene expression between EP and normal appearing endometrium in each patient was analyzed with 2(-DeltaDeltaCt) method. We found that ERalpha, ERbeta, GPR30, and PR were expressed in both normal appearing endometrium and EP in each patient. ERalpha, ERbeta, GPR30, and PR showed no difference in relative expression in EP samples compared with paired normal endometrial samples from the same uterine cavity. However, the relative expression of PR correlated with that of GPR30 (r = .70, P = .023), suggesting that the co-expression of PR and GPR30 may be a contributory mechanism in the pathogenesis of EPs at least in a subset of women.

HER-2/neu (c-erbB-2) oncoprotein in hyperplastic endometrial polyps detected in two cats.

The presence of HER-2/neu (c-erbB-2) oncoprotein, oestrogen-alpha receptor (ER), and progesterone receptor (PR) in hyperplastic endometrial polyps (EPs) of two cats with cystic endometrial hyperplasia-pyometra (CEH-P) complex was investigated. Immunohistochemistry assay for ER, PR and c-erbB-2 oncoprotein in the glandular and stromal tissue of the EPs was performed. ER and c-erbB-2 immunoreactivity was observed in the glandular epithelium of the EPs whereas PR immunoreactivity was detected only in the stromal fibroblasts. The c-erbB-2 oncoprotein may play a role with the ER in the pathogenesis of the hyperplastic EPs, although the role of this oncoprotein in the pathogenesis of EPs has yet to be determined.