Normal Endometrium Research Articles

Evaluation of Endometrial Thickness by Transvaginal Sonography in Postmenopausal Women with Bleeding: A Cross-sectional Study

Introduction: Abnormal Uterine Bleeding (AUB), occurring atleast one year after menopause, is one of the most concerning complaints among gynaecological patients. Endometrial atrophy is the most common endometrial finding in women with Postmenopausal Bleeding (PMB), approximately 10-15% of whom have endometrial carcinoma. Earlier studies suggested that obesity, Type 2 diabetes mellitus, and hypertension are risk factors for endometrial hyperplasia. Diabetes mellitus, obesity, and hypertension form the triad of endometrial cancer. Aim: To assess endometrial thickness by Transvaginal Sonography (TVS) and compare it with histopathological findings in women with PMB, evaluating whether an endometrial thickness of <4 mm on TVS is more suggestive of malignancy. Materials and Methods: The present cross-sectional study was conducted in the Department of Obstetrics and Gynaecology at King George Hospital, Vishakapatnam, Andhra Pradesh, India, from January 2022 to December 2022, comprising n=100 subjects. After routine necessary investigations for PMB, a transvaginal ultrasound examination was carried out to calculate endometrial thickness and compare it with the results of histopathological diagnosis of the endometrium. The parameters assessed were endometrial thickness and appearance, Type 2 Diabetes Mellitus (T2DM), hypertension, and Body Mass Index (BMI). The data was compiled and compared using the Chi-square test, with a p-value of ≤0.05 considered highly significant. Results: The results showed normal atrophic and thickened endometrium in 36% of subjects each, and abnormal endometrium such as hyperplasia, carcinoma, and polyps were recorded in 14%, 8%, and 6% (n=6) of cases, respectively. The histopathological results showed normal endometrium such as atrophic, secretory, and proliferative endometrium in 49%, 6%, and 19% of subjects, respectively. Abnormal endometrial findings such as endometrial hyperplasia, carcinoma, and polyps were observed in 14%, 7%, and 5% of cases, respectively. The majority of cases (58%) had endometrial thickness ≤4 mm, followed by 36% of cases with 5-10 mm and 6% of cases >11 mm, with mean and Standard Deviation (SD) values of 5.8±3. mm Statistical analysis data on the association between TVS findings and Histopathological Examination (HPE) findings was observed to be statistically significant (p<0.001). A statistically significant association was observed between T2DM, and BMI >25 kg/m2 together, DM+hypertension+BMI (Triad) and endometrial thickness, respectively. Conclusion: The TVS is easy, simple, non invasive, and involves no complications. Therefore, it can be used as the first diagnostic step in the investigations of women with PMB, combined with histopathological assessment.

Endometrial mRNA expression of key inflammatory genes and progesterone receptor in uterine tissue of bitches with endometritis

Our study aimed to evaluate the gene transcription of Cyclooxygenase 1 (COX1), cytokines (Interleukin 6 [IL6], Interleukin 8 [IL8], and Leukemia Inhibitory Factor [LIF]), and Progesterone Receptor (PR) in clinically healthy bitches with a normal endometrium and with endometritis, without the presence of cystic endometrial hyperplasia. Forty-eight mixed breed bitches in dioestrus were used. Uterine biopsies were collected for diagnosis of a normal endometrium (n=15), and endometritis (n=30). Three samples were excluded from the study (two bitches with cystic endometrial hyperplasia and one bitch with atrophy). Samples were collected by cytobrush to quantify mRNA by qPCR. Data were analyzed using a generalized mixed model. COX1, IL6, and IL8 mRNA expression in bitches with endometritis was significantly higher than in a normal endometrium (P=0.0002, P=0.002, and P=0.003, respectively). In contrast, LIF and PR mRNA expression in bitches with endometritis was significantly lower than with a normal endometrium (P=0.006 and P=0.001, respectively). IL6 (AUC 0.67) was the most favorable biomolecular marker for predicting endometritis in bitches. There was an evident change in the mRNA expression of COX1, cytokines, and PR in clinically healthy bitches with a normal endometrium and endometritis without cystic endometrial hyperplasia. These results suggest that biomolecular markers such as COX1, IL6, IL8, LIF, and PR could help diagnose endometritis in a bitch.

Effects of acupuncture and moxibustion on UHRF1 and DNMT1 in ectopic endometrium of rats with endometriosis

ObjectiveTo observe the effects of acupuncture and moxibustion on ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) and DNA methyltransferase 1 (DNMT1) in ectopic endometrium of rats with endometriosis (EMS).MethodsForty Sprague-Dawley rats were randomly divided into a sham operation group with 10 rats and a model-building group with 30 rats according to body mass. EMS rat models were established in the model-building group and then were divided into a model group, an acupuncture and moxibustion group, and a progesterone group, with 10 rats in each group. All rats were fixed by a fixator. The sham operation group and the model group were given normal saline by gavage. The acupuncture and moxibustion group received acupuncture at Xuehai (SP10) and Sanyinjiao (SP6), moxibustion at Guanyuan (CV4), and gavage of normal saline. The progesterone group was given the mixed liquid made of dydrogesterone and normal saline by gavage. After 28 d of treatments, the three diameters (length, width, and height) of EMS rats’ ectopic cysts were measured, the cyst volumes were calculated, the volumes before intervention were subtracted, and the difference values were used to evaluate the growth of ectopic cysts. UHRF1 and DNMT1 mRNA and protein levels in normal endometrium, eutopic endometrium, and ectopic endometrium were detected by real-time polymerase chain reaction and immunohistochemistry.ResultsThere was no significant difference in the ectopic cyst volume difference between the acupuncture and moxibustion group and the progesterone group (P>0.05), but they were smaller than that of the model group (P<0.05). The levels of UHRF1 and DNMT1 mRNA and protein in the ectopic endometrium of the model group were lower than those in the normal endometrium (P<0.05). The levels of DNMT1 mRNA and UHRF1 protein in the eutopic endometrium of the model group were lower than those in the normal endometrium (P<0.05). The levels of UHRF1 mRNA and protein and the level of DNMT1 protein in the ectopic endometrium of the acupuncture and moxibustion group were higher than those in the model group (P<0.05), and the level of UHRF1 mRNA was higher than that in the progesterone group (P<0.05). The level of DNMT1 mRNA in the eutopic endometrium of the acupuncture and moxibustion group was higher than that in the model group (P<0.05). The levels of UHRF1 and DNMT1 mRNA and protein in the acupuncture and moxibustion group were insignificantly different from those in the normal endometrium (P>0.05).ConclusionAcupuncture and moxibustion may up-regulate the levels of UHRF1 mRNA and UHRF1 and DNMT1 proteins in the ectopic endometrium to the normal level so as to reduce the volume of ectopic cysts and cure endometriosis in rats.

Activation of HAND2-FGFR signaling pathway by lncRNA HAND2-AS1 in adenomyosis†.

Heart and neural crest derivatives expressed transcript 2 (HAND2) is a critical mediator of progesterone action in endometrial stromal cells. Silencing of Hand2 expression in mouse uterus leads to an unopposed FGFR-mediated action that causes female mice infertility. To investigate the involvement of HAND2-FGFR signaling in pathogenesis of adenomyosis, immunohistochemistry, in situ hybridization, and quantitative real-time PCR were employed to assess gene expression in the normal endometrium, the paired eutopic endometrium and ectopic lesions obtained from women with adenomyosis. DNA methylation in the regions of HAND2 promoter and the first exon was also monitored in these samples. Our results revealed that HAND2 expression were dramatically reduced, but FGF9 expression and FGFR-ERK1/2-mediated MAPK signaling pathway were enhanced in the eutopic endometrium and ectopic lesions of patients with adenomyosis compared to the normal controls. Interestingly, expression of HAND2-AS1, a long noncoding RNA that resides adjacent to HAND2 in genome, was also reduced in adenomyosis. DNA methylation analysis revealed that the bidirectional promoter between HAND2 and HAND2-AS1, and the first exon of HAND2 gene was heavily methylated in the eutopic endometrium and the ectopic lesions of adenomyosis. To investigate the regulation of gene expression by HAND2-AS1, HAND2-AS1 expression was silenced in human endometrial stromal cells. In contrast to the downregulation of HAND2 in response to HAND2-AS1 silencing, FGF9 expression was augmented significantly. Endometrial stromal cells lacking HAND2-AS1 exhibited enhanced proliferation and migration potentials. Collectively, our studies revealed a new molecular mechanism by which HAND2-AS1 is involved in the pathogenesis of adenomyosis via modulating HAND2-FGFR-mediated signaling.

#125 : The Role of BDNF Receptors in the Incidence of Endometrioma Tissue Invasion Onto the Chorioallantoic Membrane

Background and Aims: Previous studies have explored the role of neurotrophins and their receptors, especially in forming deep endometriosis, endometriosis tissue invasion, and its effects on tissue proliferation. However, these studies do not include research on the pathogenesis of endometriomas. We tried to model the invasion of endometrioma tissue to find out more about its pathogenesis by using the chorioallantoic membrane (CAM) as the host. Immunohistochemistry (IHC) to detect neurotrophin BDNF and its receptors, namely TrkB and P75, are employed and linked between their expression and the process of invasion and proliferation. Method: The endometriotic tissue samples were collected from women (n=27) who underwent hysteroscopy/laparoscopy at Dr. Sardjito Central Hospital. Peritoneal endometriosis (PE) lession, endometrioma (CC), and eutopic endometrium (EN) was analyzed with 15 tissue samples in each group. Samples were placed in a tube containing transport medium and transplanted into CAM of fertile chicken eggs for five days. Transplanted tissue was harvested, and histological preparations were made using the paraffin method. IHC staining was performed on p75, Ki67, TrkB, and BDNF staining. Invasion analysis and IHC evaluation were performed with a semi-quantitative method. Data were analyzed using IBMⓇ SPSS Statistics version 25.0. Statistical significance was accepted at P &lt; 0.05. Results: Normal Endometrium expressed the highest expression of BDNF than peritoneal endometriosis and endometrioma (0.36± 0.38, 0.16± 0.13, 0.07± 0.07, P=0.007). The P75 expression correlated positively with Ki67 expression in PE and CC samples (P=0.012; P=0.008). Conclusion: The p75 receptor may have a role in endometriosis tissue proliferation, but this receptor does not directly influence tissue invasion into CAM. While proliferation in endometriomas positively correlates with invasion into CAM, it is not correlated with peritoneal endometriosis.

Enhancing endometrial pathology detection: chromohysteroscopy vs. conventional hysteroscopy in infertility evaluation

BackgroundEndometrial pathology is a recognized contributor to infertility and recurrent implantation failure, but its detection during hysteroscopy, particularly in the absence of visible lesions, is challenging. Chromohysteroscopy, involving the use of methylene blue dye, has shown promise in improving diagnostic accuracy.MethodsThis interventional cross-sectional study compared the diagnostic accuracy of chromohysteroscopy and conventional hysteroscopy, using histopathology as the gold standard. A total of 100 consenting infertility patients were included, in a sequential step, hysteroscopy followed by chromohysteroscopy using methylene blue dye was performed to enhance the detection of subtle endometrial pathologies.ResultsAmong the 100 women who underwent diagnostic hysteroscopy, 76 exhibited normal findings, while 24 had abnormal findings. During chromohysteroscopy, 62 cases displayed a light staining pattern, and 38 cases exhibited dark staining. Histopathological analysis of biopsy tissue from the dark-stained areas revealed endometrial pathology in 84.2% (32/38) and normal endometrium in 15.8% (6/38) cases. In contrast, biopsies from the light-stained areas indicated abnormal endometrium in only 3.23% (2/62) cases, with the remaining 96.77% having a normal histology. Chromohysteroscopy demonstrated a significantly higher diagnostic accuracy (92%) for endometrial pathology compared to conventional hysteroscopy (58%). Notably, chromohysteroscopy’s sensitivity was 94.12%, and its specificity was 90.9%. The staining patterns observed during chromohysteroscopy correlated well with histological findings, highlighting its effectiveness in identifying structurally damaged endometrium.ConclusionChromohysteroscopy emerges as a valuable diagnostic tool for assessing endometrial pathology, especially in infertility cases. This technique offers superior accuracy compared to conventional hysteroscopy, providing clinicians with a more precise means of diagnosis and potential targeted treatments.

MORPHOLOGICAL AND IMMUNOHISTOCHEMICAL CHARACTERISTICS OF ENDOMETRIAL LAYERS IN WOMEN OF REPRODUCTIVE AGE WITH ENDOMETRIAL HYPERPLASIA WITHOUT ATYPIA

Immunohistochemical staining may be useful for the differential diagnosis of endometrial hyperplasia (EH) without/with atypia and carcinoma. Several immunohistochemical biomarkers have already been investigated for use as diagnostic adjuncts in the diagnosis and classification of EH and may also predict progression from EH to carcinoma. However, the optimal molecular biomarker would be one that could reliably distinguish between hyperplastic benign with/without risk of recurrence, precancerous (hyperplastic atypical) and malignant endometrium, and indicate/predict transition between these three groups. To date, no candidate has been found to fully fill this role, so the search is ongoing.&#x0D; Aim. To study the morphological and immunohistochemically features of the structure of all layers of the endometrium, divided into functional and non-functional zones, which may have an impact on the development of endometrial hyperplasia&#x0D; Materials and methods. The study was performed on endometrial morphological material obtained by diagnostic biopsy from 21 women with abnormal uterine bleeding (AUB) in the gynecological department of the Dnipro Clinical Hospital No. 9 in Dnipro during 2022-2023. The study investigated the expression of the biomarkers ER, PgR, Ki67, CK7, and CK8 in women with endometrial hyperplasia without atypia and secretory endometrium.&#x0D; Results. In women with EH without atypia, the expression of ER in the stroma spontaneously increases, while epithelial cells do not show sensitivity to estrogen. The expression of PgR in the glands spontaneously increases, while the expression of PgR in the stroma is low. This may indicate that stromal cells may be less sensitive to progesterone. High expression of Ki67 in endometrial hyperplasia causes active processes of cell proliferation, while low expression of Ki67 in normal endometrium indicates its physiological state. These data can be useful for diagnosis and detection of pathological changes of the endometrium. SK7 is expressed in epithelial cells, even with increased numbers. Normally, during functional observations of the endometrium, the expression of SK7 in epithelial cells is also observed. The functional zone is a layer of the endometrium that undergoes cyclical changes depending on the menstrual cycle of a woman. In this case, there is a regular renewal of cells expressing CK7, which remains one of the typical markers of epithelial cells. The analysis of SK7 expression allows us to detect differences in the processes of cell proliferation and differentiation between endometrial hyperplasia without atypia and normal endometrium. These data coincide with the findings of other authors, are important for a deeper identification of pathophysiological mechanisms associated with endometrial hyperplasia, and also include additional markers for the diagnosis and prognosis of this condition.&#x0D; Conclusion The study results suggest that the expression of ER, PgR, Ki67, CK7, and CK8 may be associated with the development of EH without atypia. Further studies are needed to confirm these findings and to investigate the role of other biomarkers in the pathogenesis and diagnosis of EH.

NADPH oxidase 4-mediating oxidative stress contributes to endometriosis.

NADPH oxidase 4 (NOX4) plays an important role in the regulation of oxidative stress, which is associated with endometriosis. This study aims to investigate the effects of NOX4 in endometriosis and its molecular mechanisms. Clinical specimens were collected, and human endometrial stromal cells (HESCs) were isolated. The knockdown of NOX4 cell lines was established on the HESCs and induced by peritoneal fluid. The levels of NOX4 were determined by using immunohistochemistry (IHC) staining, western blotting, and qPCR, respectively. The levels of oxidative stress markers were determined by using western blotting and ELISAs, respectively. The correlation of NOX4 and oxidative stress markers was analyzed by the Pearson correlation coefficient. The levels of NOX4 were dramatically elevated in the ectopic endometrium. Besides, oxidative stress biomarkers were also dysregulated in the ectopic endometrium as compared to the normal endometrium. Pearson's correlation coefficient analysis revealed a relationship between NOX4 and oxidative stress biomarkers in the ectopic endometrium. NOX4 modulated the expressions of oxidative stress markers in endometrial stromal cells stimulated by the peritoneal fluid from endometriosis. The effects of NOX4 on endometriosis are in part by its regulatory effects against oxidative stress.

Characterization of a fluorescence imaging probe that exploits metabolic dependency of ovarian clear cell carcinoma

The purpose of this study is to clarify the metabolic dependence of ovarian clear cell carcinoma (CCC) by comparing normal tissues and to examine the applicability of fluorescence imaging probe to exploit these metabolic differences. Enhanced glutathione synthesis was supported by the increased uptake of related metabolites and elevated expression levels of genes. Accumulation of intracellular iron and lipid peroxide, induction of cell death by inhibition of the glutathione synthesis pathway indicated that ferroptosis was induced. The activation of γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG), a fluorescent imaging probe that recognizes γ-glutamyl transferase, which is essential for the synthesis of glutathione, was investigated in fresh-frozen surgical specimens. gGlu-HMRG detected extremely strong fluorescent signals in the tumor lesions of CCC patients, compared to normal ovaries or endometrium. These results revealed that CCC occurs in the stressful and unique environment of free radical-rich endometrioma, and that glutathione metabolism is enhanced as an adaptation to oxidative stress. Furthermore, a modality that exploits these metabolic differences would be useful for distinguishing between CCC and normal tissues.

The Evaluation of Endometrial Sampler SAP-1 in Screening Patients With General Risk of Endometrial Cancer: A Diagnostic Test Study

Objectives: In recent years, early screening for endometrial cancer (EC) has received increasing attention. EC screening is recommended to be conducted among high-risk and risk-increasing populations, while the general-risk population, even with symptoms, is not within the scope of screening. This study aims to explore the role of endometrial sampler SAP-1 as a sample-collecting tool to screen EC among patients with general risk. Materials and Methods: From August 2018 to June 2023, 275 patients, who were hospitalized for undergoing hysteroscopy and were confirmed as having a general risk of EC, were enrolled in this retrospective study. Before the procedure, endometrial samples were firstly collected by the method of SAP-1, and then hysteroscopy curettage or electrotomy was conducted to gather endometrial samples. With the pathological results of the latter as the gold standard, the diagnostic efficacy of SAP-1 sampling was analyzed. Results: The sample satisfaction rate of SAP-1 was 91.4%, slightly lower than that by method of hysteroscopy (95.1%), but there was no significant difference between the two methods (P&gt;0.05). The samples of 275 cases were satisfied with both methods. One case of endometrial carcinoma and one case of precancerous lesion were misdiagnosed as normal endometrium with SAP-1 sampling. The sensitivity, specificity and accuracy of SAP-1 in diagnosing endometrial carcinoma and precancerous lesions were 88.2%, 100% and 99.3%, respectively. Conclusions: Applying endometrial sampler SAP-1 to screen EC among women with general risk of EC has high diagnostic efficiency, easy manipulation, high safety, and can be completed in outpatient service with outstanding cost-effectiveness, which as well is worthy of clinical promotion.

Clinical Characteristics and Endometrial Lesions of Postmenopausal Patients with Abnormal Uterine Bleeding

This study delves into factors linked to abnormal uterine bleeding and endometrial issues during perimenopause. Analyzing clinical data from 333 perimenopausal patients with abnormal uterine bleeding, we identified key variables influencing endometrial lesions. Of these cases, 26.1% exhibited normal endometrium, while 63.1% had benign lesions (including polyps, leiomyomas, and hyperplasias), and 10.5% presented with endometrial cancer. Single-factor analysis revealed correlations between factors like age, BMI, parity, hypertension history, IUD usage, family cancer history, bleeding duration, endometrial characteristics, and tumor markers, and distinct endometrial changes (P &lt;0.05). Multivariate analysis emphasized the significance of age groups (40–45, 45–50, 50–55 years) and endometrial thickness on benign and malignant lesions (P &lt;0.05). As perimenopausal abnormal uterine bleeding rises, early detection of these factors and the establishment of an effective diagnostic and treatment framework will greatly enhance the well-being of perimenopausal women.

Hepcidin as a key regulator of iron homeostasis triggers inflammatory features in the normal endometrium

Menstrual blood, containing high iron levels, can undergo retrograde transport into the abdominal cavity. Excess iron causes oxidative stress and inflammation. Iron metabolism is regulated by hepcidin, and serum hepcidin levels are increased in patients with endometriosis; however, the functions of hepcidin in normal endometrium remain unclear. We therefore aimed to examine hepcidin concentrations in patients with endometriosis and to determine if iron accumulation and hepcidin increased the production of reactive oxygen species (ROS) and inflammation in normal endometrial cells. We determined hepcidin levels in peritoneal fluid and menstrual blood from patients with and without endometriosis (25/16 and 15/15 patients, respectively). We also examined the effects of hepcidin on ferroportin expression, iron accumulation, and ROS generation in normal endometrial stromal cells (NESCs) from 20 women who underwent surgery for uterine leiomyoma, using immunohistochemistry and immunofluorescence analyses and analyzed its effect on the expression of inflammatory cytokines by real-time polymerase chain reaction. There was no significant difference in iron concentrations in menstrual blood or peritoneal fluid between women with and without endometriosis; however, women with endometriosis had significantly higher hepcidin levels in menstrual blood. Hepcidin reduced the expression of ferroportin in NESCs and promoted the accumulation of ferrous iron. Hepcidin plus ferrous iron increased the production of ROS and inflammatory cytokines compared with ferrous iron alone. These results indicate that women with endometriosis have high hepcidin levels in menstrual blood, leading to increased iron production, oxidative stress, and inflammation, which may, in turn, promote the development of endometriosis.

Deep molecular tracking over the 12-yr development of endometrial cancer from hyperplasia in a single patient.

Although the progressive histologic steps leading to endometrial cancer (EndoCA), the most common female reproductive tract malignancy, from endometrial hyperplasia are well-established, the molecular changes accompanying this malignant transformation in a single patient have never been described. We had the unique opportunity to investigate the paired histologic and molecular features associated with the 12-yr development of EndoCA in a postmenopausal female who could not undergo hysterectomy and instead underwent progesterone treatment. Using a specially designed 58-gene next-generation sequencing panel, we analyzed a total of 10 sequential biopsy samples collected over this time frame. A total of eight pathogenic/likely pathogenic mutations in seven genes, APC, ARID1A, CTNNB1, CDKN2A, KRAS, PTEN, and TP53, were identified. A PTEN nonsense mutation p.W111* was present in all samples analyzed except histologically normal endometrium. Apart from this PTEN mutation, the only other recurrent mutation was KRAS G12D, which was present in six biopsy samplings, including histologically normal tissue obtained at the patient's first visit but not detectable in the cancer. The PTEN p.W111* mutant allele fractions were lowest in benign, inactive endometrial glands (0.7%), highest in adenocarcinoma (36.9%), and, notably, were always markedly reduced following progesterone treatment. To our knowledge, this report provides the first molecular characterization of EndoCA development in a single patient. A single PTEN mutation was present throughout the 12 years of cancer development. Importantly, and with potential significance toward medical and nonsurgical management of EndoCA, progesterone treatments were consistently noted to markedly decrease PTEN mutant allele fractions to precancerous levels.

Involvement of small leucine-rich proteoglycans and telocytes in thin and thick human endometrium: immunohistochemical and ultrastructural examination

ABSTRACT Thin endometrium, defined as an endometrial thickness of less than 7 mm during the late follicular phase, is a common cause of frequent cancelation of embryo transfers or recurrent implantation failure during assisted reproductive treatment. Small proteoglycans regulate intracellular signaling cascades by bridging other matrix molecules and tissue elements, affecting cell proliferation, adhesion, migration, and cytokine concentration. The aim of the study is to investigate the role of small leucine-rich proteoglycans in the pathogenesis of thin and thick human endometrium and their differences from normal endometrium in terms of fine structure properties. Normal, thin, and thick endometrial samples were collected, and small leucine-rich proteoglycans (SLRPs), decorin, lumican, biglycan, and fibromodulin immunoreactivities were comparatively analyzed immunohistochemically. The data were compared statistically. Moreover, ultrastructural differences among the groups were evaluated by transmission electron microscopy. The immunoreactivities of decorin, lumican, and biglycan were higher in the thin endometrial glandular epithelium and stroma compared to the normal and thick endometrium (p < .001). Fibromodulin immunoreactivity was also higher in the thin endometrial glandular epithelium than in the normal and thick endometrium (p < .001). However, there was no statistical difference in the stroma among the groups. Ultrastructural features were not profoundly different among cases. Telocytes, however, were not seen in the thin endometrium in contrast to normal and thin endometrial tissues. These findings suggest a possible role of changes in proteoglycan levels in the pathogenesis of thin endometrium.

FZD7: A potential biomarker for endometriosis.

Endometriosis is a chronic inflammatory, benign disorder that often co-occurs with adenomyosis and/or leiomyoma. The overall incidence of endometriosis in reproductive period women was nearly 10%. However, the exact mechanisms of endometriosis-associated pathogenesis are still unknown. In this study, we aimed to investigate whether Frizzled-7 (FZD7) would effectively promote the development of endometriosis. The microarray-based data analysis was performed to screen endometriosis-related differentially expressed genes. This process uncovered specific hub genes, and the nexus of vital genes and ferroptosis-related genes were pinpointed. Then, we collected human endometrial and endometriotic tissues from patients with endometriosis of the ovary (n = 39) and control patients without endometriosis (n = 10, who underwent hysterectomy for uterine fibroids) to compare the expression of FZD7. These findings indicated that the expression of FZD7 was high compared with normal endometrium, and FZD7 may promote the progression of endometriosis. FZD7 may serve as a potential therapeutic target for endometriosis treatment.

Retracted: A Comparative Study of Endometriosis and Normal Endometrium Based on Ultrasound Observation.

[This retracts the article DOI: 10.1155/2022/7934690.].

Dynamics of HOXA10 expression in ectopic endometrium of a mouse model of endometriosis

Introduction: Homeobox gene A10 (HOXA10) is a transcription factor that plays a key role in maintaining endometrial homeostasis. In women with endometriosis, HOXA10 expression is downregulated, which is thought to cause progesterone resistance. However, it is unknown whether this downregulation is a cause or consequence of endometriosis. Materials and Methods: In this study, we used a mouse model of endometriosis and demonstrated that compared to the normal endometrium, the expression of HOXA10 is progressively downregulated during lesion development (from day 10 to day 65). Results: We observed that the expression of HOXA10 is lower in both well-differentiated and mixed types of endometriosis. During lesion development, the levels of HOXA10 were initially downregulated in epithelial cells more than in stromal cells. However, as the lesion development progressed further, the stromal expression was drastically reduced. While the nucleocytoplasmic ratio of HOXA10 was identical between control and endometriosis lesions at the initial stages, at later time points, HOXA10 remained largely nuclear, with little expression in the stroma. Conclusion: We conclude that the downregulation of HOXA10 is a consequence of endometriosis and may contribute toward its pathogenesis.

Sonographic evaluation of abnormal uterine bleeding among non-pregnant women in Lagos, Southwest, Nigeria

Abnormal uterine bleeding (AUB) is the direct cause of a significant healthcare burden for women and society at large. Around 30% of women will experience AUB during their reproductive years, prompting them to seek medical attention. Abnormal Uterine Bleeding can significantly impact their quality of life, often causing frequent work absences and potentially requiring surgical treatment. It's crucial to accurately diagnose the underlying cause of AUB in this age group to ensure proper and effective management. This study aims to evaluate AUB among non-pregnant women in Lagos using transvaginal ultrasound. A descriptive cross-sectional study of 152 non-pregnant women of reproductive age (16 to 55 years) with abnormal uterine bleeding for a period of five months. A purposive sampling technique was used to recruit the subjects. Data was analysed using SPSS version 20.0. Sonographic evaluation reveals positive findings in 97 cases (63.8%) out of 152 cases studied. Seventy cases (46%) had structural abnormalities with the highest being Leiomyoma (41.4%), followed by Adenomyosis (3.9%), and Endometrial Polyp (0.6%). The age group 26 – 35 years presented most with abnormal uterine bleeding cases (48.6%). The major clinical history was absent menstrual bleeding with findings depicting normal endometrium. There was a positive and moderate correlation between age and parity of subjects with AUB. The study found that Transvaginal ultrasound effectively identifies AUB's structural causes. It is recommended as the initial assessment method due to its safety, affordability, and widespread availability in healthcare settings.

Identification of Potentially Novel Molecular Targets of Endometrial Cancer Using a Non-Biased Proteomic Approach.

The present study was aimed at identifying novel proteins in endometrial cancer (EC), employing proteomic analysis of tissues obtained after surgery. A differential MS-based proteomic analysis was conducted from whole tissues dissected from biopsies from post-menopausal women, histologically confirmed as endometrial cancer (two endometrioid and two serous; n = 4) or normal atrophic endometrium (n = 4), providing 888 differentially expressed proteins with 246 of these previously documented elsewhere as expressed in EC and 372 proteins not previously demonstrated to be expressed in EC but associated with other types of cancer. Additionally, 33 proteins not recorded previously in PubMed as being expressed in any forms of cancer were also identified, with only 26 of these proteins having a publication associated with their expression patterns or putative functions. The putative functions of the 26 proteins (GRN, APP, HEXA, CST3, CAD, QARS, SIAE, WARS, MYH8, CLTB, GOLIM4, SCARB2, BOD1L1, C14orf142, C9orf142, CCDC13, CNPY4, FAM169A, HN1L, PIGT, PLCL1, PMFBP1, SARS2, SCPEP1, SLC25A24 and ZC3H4) in other tissues point towards and provide a basis for further investigation of these previously unrecognised novel EC proteins. The developmental biology, disease, extracellular matrix, homeostatic, immune, metabolic (both RNA and protein), programmed cell death, signal transduction, molecular transport, transcriptional networks and as yet uncharacterised pathways indicate that these proteins are potentially involved in endometrial carcinogenesis and thus may be important in EC diagnosis, prognostication and treatment and thus are worthy of further investigation.

Single-cell profiling identifies distinct hormonal, immunologic, and inflammatory signatures of endometriosis-constituting cells.

Endometriosis consists of ectopic endometrial epithelial cells (EEECs) and ectopic endometrial stromal cells (EESCs) mixed with heterogeneous stromal cells. To address how endometriosis-constituting cells are different from normal endometrium and among endometriosis subtypes and how their molecular signatures are related to phenotypic manifestations, we analyzed ovarian endometrial cyst (OEC), superficial peritoneal endometriosis (SPE), and deep infiltrating endometriosis (DIE) from 12 patients using single-cell RNA-sequencing (scRNA-seq). We identified 11 cell clusters, including EEEC, EESC, fibroblasts, inflammatory/immune, endothelial, mesothelial, and Schwann cells. For hormonal signatures, EESCs, but not EEECs, showed high estrogen signatures (estrogen response scores and HOXA downregulation) and low progesterone signatures (DKK1 downregulation) compared to normal endometrium. In EEECs, we found MUC5B+ TFF3low cells enriched in endometriosis. In lymphoid cells, evidence for both immune activation (high cytotoxicity in NK) and exhaustion (high checkpoint genes in NKT and cytotoxic T) was identified in endometriosis. Signatures and subpopulations of macrophages were remarkably different among endometriosis subtypes with increased monocyte-derived macrophages and IL1B expression in DIE. The scRNA-seq predicted NRG1 (macrophage)-ERBB3 (Schwann cell) interaction in endometriosis, expressions of which were validated by immunohistochemistry. Myofibroblast subpopulations differed according to the location (OECs from fibroblasts and SPE/DIEs from mesothelial cells and fibroblasts). Endometriosis endothelial cells displayed proinflammation, angiogenesis, and leaky permeability signatures that were enhanced in DIE. Collectively, our study revealed that (1) many cell types-endometrial, lymphoid, macrophage, fibroblast, and endothelial cells-are altered in endometriosis; (2) endometriosis cells show estrogen responsiveness, immunologic cytotoxicity and exhaustion, and proinflammation signatures that are different in endometriosis subtypes; and (3) novel endometriosis-specific findings of MUC5B+ EEECs, mesothelial cell-derived myofibroblasts, and NRG1-ERBB3 interaction may underlie the pathogenesis of endometriosis. Our results may help extend pathologic insights, dissect aggressive diseases, and discover therapeutic targets in endometriosis. © 2023 The Pathological Society of Great Britain and Ireland.