Impact of Luteinized Unruptured Follicles on Endometrial Receptivity

This study examined the impact of luteinized unruptured follicle （LUF） on endometrial receptivity. The menstrual cycle of 17 LUF patients （LUF group） and 13 ovulatory women （control group） was monitored by measuring LH level in urine and by ultrasonic examination. An endometrial biopsy at the sixth to tenth day after LH surge was taken in all the patients. The expressions of endometrial ER, PR and integrin ανβ3 were immunohistochemically determined. At the same time, the serum levels of E2 and P were detected by chemiluminescence. The results exhibited that （1） The mean serum P level in LUF group （7.32±2.56 ng/mL） was significantly lower than that in control group （11.17±3.17 ng/mL） （P0.01）. But there was no significant difference in the mean serum E2 levels between LUF group （179.35±81.60 pg/mL） and the control group （198.58±75.23 pg/mL） （P0.05）; （2） The mean expression intensities of ER, PR in endometrium of LUF group （183.86±2.43, 167.94±3.04） were significantly higher than those in control group （109.35±6.31, 105.98±4.07） （P0.01）; （3） The mean expression intensities of integrin ανβ3 in endomtrium of LUF patients （114.90±11.38） were significantly lower than those in control group （191.34±1.82） （P0.01）; （4） The change profile of integrin ανβ3 expression in the endometrium of LUF patients was in positive relation with serum P level （r=0.77, P0.01）, but bore no significant relationship with serum E2 level （r=0.01, P0.05）. It was concluded that the depression of serum P levels in LUF patients was closely related to the failure of the down-regulation of ER and PR, and the low expressions of integrin ανβ3 also suggested that the delayed implantation and the impaired endometrial receptivity had impact on embryonic implantation.

Assessment of Uterine Receptivity by Endometrial and Subendometrial Blood Flows Measured by Vaginal Color Doppler Ultrasound in Women Undergoing IVF Treatment

Objective To evaluate endometrial and subendometrial blood flows measured by vaginal color Doppler ultrasound as a predicator of endometrial receptivity in women undergoing IVF treatment. Methods A total of 119 infertile patients undergoing the first IVF/ICSI-ET cycle were recruited. Three groups were divided according to a color Doppler ultrasound examination performed on the day of hCG injection. Group A, endometrial and subendometrial blood flows were 2 branches and below; group B, endometrial and subendometrial blood flows were between 3 and 4 branches; group C, endometrial and subendometrial blood flows were 5 branches and above. Patients were transferred 1-3 embryos each. Demographic data, ovarian responses, endometrial thickness, PI, RI, development of embryo and IVF result among groups were compared. Results Demographic data, ovarian responses, endometrial thickness, PI, RI and development of embryo among groups have no significant difference. The pregnancy rate of group A was significantly lower than that of group B （P〈0.05） and group C （P〈0.01）. The implantation rate of group A was significantly lower than than of group C （P〈0.01）. There was no significant difference of the rate of pregnancy and implantation between group B and group C （P〉0.05）. Conclusion Endometrial and subendometrial blood flows measured by vaginal color Doppler ultrasound is a good predicator of pregnancy during IVF treatment. A good endometrial and subendometrial blood flows is benefit for the result of IVF.

Value of Intrauterine Autologous Platelet-Rich Plasma Therapy on Endometrial Receptivity:A Literature Review

Endometrial receptivity is an important factor that influences embryo implantation.Thus,it is important to identify an applicable approach to improve endometrial receptivity in women undergoing assisted reproductive technology.Recently,growing evidence has indicated that intrauterine platelet-rich plasma(PRP)infusion is an effective method to obtain a satisfactory reproductive outcome by increasing endometrial thickness and improving endometrial receptivity.Therefore,the present review aims to outline the possible mechanisms of PRP on endometrial receptivity and summarize the present literature on the effects of PRP therapy in improving endometrial receptivity.

Endometrial Injury and Sub Endometrial Doppler Study to Predict Uterine Receptivity in Women with Unexplained Infertility: A Randomized Controlled Trial

Objectives: The aim of this work was to compare the effectiveness and safety of endometrial scratching at different times of the menstrual cycle on cumulative pregnancy rate and also to assess and clarify its relationship and effect on sub-endometrial vasculature blood flow by Doppler ultrasound, in cases of unexplained infertility attempting to conceive spontaneously (without ovulation induction). Study Design: A prospective randomized clinical control study. Patients and Methods: A total of 252 eligible participants were included in the study and randomly allocated using block randomization into three groups: Group A (n = 84): endometrial scratching was performed during the pre-ovulatory days and Group B (n = 84): endometrial scratching has been done at day 7 of the cycle. Group C (control group): includes 84 cases without endometrial scratching. The Doppler ultrasound will be done. The pulsatility index (PI) and resistance index (RI) of endometrial and sub endometrial arteries were calculated. All women were followed up to 3 months. Results: Cumulative pregnancy rate is 21.42% and 28.57% in the study groups A and B respectively which is higher than group C (control group) (4.76%) but with statistically insignificant P-value = 0.254. There is statistically significant difference in RI & PI between the studied groups and the control group on day 13 (P value < 0.001). There is statistically significant difference in PI between day 13 and day 6 for the same group in both groups (A&B) (P value < 0.003), while there is no statistically significant difference in Group C (P value = 0.156). Conclusion: Endometrial scratching is a cost-effective and easy technique which may improve clinical pregnancy rates and endometrial blood flow in women with unexplained infertility.

Surgical and nutritional interventions for endometrial receptivity:A case report and review of literature

BACKGROUND Polycystic ovary syndrome(PCOS)is an endocrine disease that combines metabolic,reproductive,and psychological dysfunctions.Ovulation disorders and impaired endometrial receptivity in PCOS can cause infertility.Insulin resistance(IR)is a pathological state of inadequate response to insulin that affects reproduction in PCOS,as damage caused by IR at the endometrial level becomes an obstacle for embryo implantation.Reversing IR resulted in spontaneous pregnancies in PCOS patients,indicating that metabolic corrections improve endometrial dysfunctions.Mesenchymal stem-cell treatment has also corrected endometrial quality and lead to pregnancies in patients with Asherman’s syndrome.We propose a combination of nutritional intervention with the surgical placement of stem cells to improve endometrial quality to achieve pregnancy in a PCOS patient undergoing in vitro fertilization(IVF)treatment.CASE SUMMARY After two failed IVF cycles,a metabolic intervention,consisting of a ketogenic diet with daily consumption of 50 g of carbohydrates(CH),was indicated until pregnancy.Metabolic Syndrome was assessed using the Harmonizing Definition(3 of 5 pathologies:Central obesity,hypertension,hyperglycemia,hypertriglyceridemia,and dyslipidemia),and the Homeostatic Model Assessment of IR(HOMA-IR)was used to measure the level of IR.Once IR improved,endometrial quality improved.However,two day 5-thawed embryos(euploid,donated oocyte–partner's sperm)failed to implant,suggesting endometrial quality improvement was insufficient.Therefore,transmyometrial implantation of mesenchymal stem cells from the stromal vascular fraction of adipose tissue was performed to enrich the endometrial stem cell niche.Minimal endometrial mean thickness for embryo transfer(6.9 mm)was achieved three months after stem cell treatment and continuous dietary control of IR.Two euploid-day 5-thawed embryos(donated oocyte–partner's sperm)were transferred,and embryo implantation was confirmed on day 14 byβ-hCG serum levels.Currently,a 37 wk baby girl is born.CONCLUSION In PCOS,endometrial quality can be improved by combining nutrient-based metabolic correction with endometrial stem cell niche enrichment.

Network pharmacology-based prediction and verification of the mechanism for Bushen Chengyun granule on low endometrial receptivity

Objective:Bushen Chengyun granule(BCG)is an empirical treatment for female infertility(FI)caused by low endometrial receptivity(LER)involving a poorly understood mechanism.In this study,network pharmacology was used to explore the potential therapeutic mechanism of BCG on FI caused by LER.Methods:The corresponding herb targets were obtained by conducting a search in the Traditional Chinese Medicine Systems Pharmacology Database and PubMed-reported literature.Disease targets were obtained from the following databases:Comparative Toxicogenomics Database,Human Phenotype Ontology,and Therapeutic Target Database.Treatments for LER using BCG have used target matching(BCG e LER target).Then,the predicted targets were uploaded to the Search Tool for the Retrieval of Interacting Genes/Proteins database for gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses.Furthermore,triptorelin acetate for injection t menotrophin t chorionic gonadotropin for injection were used to establish a mouse model of blastocyst implantation disorder and to evaluate the in vivo effect of BCG on blastocyst implantation.Results:Overall,156 bioactive chemical components and 1092 targets of BCG were identified.The results indicated that 482 biological processes(FDR<0.01)and 15 pathways(FDR<0.01)related to BCG participated in the complex treatment effects and were associated with the endocrine system,inflammatory responses,metabolism,apoptosis,ovulatory performance,and angiogenesis.Moreover,16 hub nodes of BCG including estrogen receptor(ESR1),estrogen receptor beta(ESR2),progesterone receptor,et al,were recognized as potential treatment targets and might help clarify the underlying therapeutic mechanisms of BCG for female infertility.BCG significantly increased the protein expressions of estrogen receptors and progesterone receptors.Conclusions:These findings reveal the potential therapeutic mechanism of BCG for female infertility involves low endometrial receptivity,which should be evaluated further.

EFFECT OF MIFEPRISTONE (RU486)ON MARKERS OF ENDOMETRIAL RECEPTIVITY

Objective To study the effect of single and low dose of RU486 on endometrial receptivity of healthy women. Methods A total of 5 healthy women were followed for one control and one treatment cycle. In the treatment cycle, a dose of 10 mg RU486 was administered on day luteinizing hormone (LH)-2. In both the control and treatment cycle, an endometrial biopsy was obtained on LH+7. These biopsies were assessed by immunohistochemical analysis to find the difference in expression of integrins and progesterone receptor (PR) between the control and treatment cycle. Results The treatment with RU486 increased the expression of α 1 and α 4 subunits of integrin in glandular epithelial cells, but did not influence β 3 subunit. Moreover, the normal down regulation of PR in epitherial cell nuclei was inhibited by 10 mg RU486. Conclusion Single dose of 10 mg RU486 impairs the establishment of endometrial receptivity on time.

Study of Endometrial Receptivity during Implantation in Implantation Dysfunction Mouse

Objective To establish the mice model of implantation dysfunction and to study the endometrial receptivity during implantation in implantation dysfunction mouse. Methods Sexually mature female virgin, Kunming mice were randomly assigned to the control group and the model group postcoitally. The model mice at 9 ： 00 AM on d 4 of pregnancy（d 4） were injected subcutaneously with mifepristone. All animals were sacrificed at 9 ：00 PM on d 4 and their uterine horns were examined for the presence of implanted embryos. Histopathology of uterine endometrium was observed by light-microscope. The endometrial expressions of estrogen receptor （ER） and progesterone receptor （PR） assessed by immunnohistochemical SP method. The endometrial expressions of ER mRNA and PR mRNA were assessed by semi-quantitative reverse transcriptase polymerase chain reaction （RT-PCR）. Results Compared with control group, implantation rates and average embryo num- ber significently decreased in model group, the development of endometrium was inhibited. In model group, absorbency and area rate of ER and PR in the gland and stroma were lower than those in control group （P〈0.05）. Expressions of ER mRNA and PR mRNA in model uterus were significantly lower than those in the control. Conclusion The endometrial receptivity and implantation decreased in mifepristoneinduced implantation dysfunction mouse.

A meta-analysis on the improvement of endometrial receptivity of PCOS by Bushen recipe combined with Clomiphene

Objective: To systematically evaluate the efficacy and safety of Bushen Recipe combined with clomiphene compared with clomiphene in improving endometrial receptivity of polycystic ovary syndrome. Methods: The time limit is from the establishment of the database to January 2, 2020. A randomized controlled trial was conducted to compare the effects of Bushen Recipe combined with clomiphene and clomiphene on the endometrial receptivity of polycystic ovary syndrome (PCOS). Meta analysis was performed with RevMan5.3 software. Results: A total of 13 RCTS were included, with a total of 797 PCOS patients. The results of this meta-analysis show: there were statistically significant differences in the improvement of endometrial thickness [WMD=1.62,95%CI(1.22, 2.01), P <0.00001], endometrial type[RR=1.51,95%CI(1.28, 1.78), P <0.00001], uterine artery pulse index(PI) [WMD=-0.18,95%CI(-0.27, -0.09) , P <0.0001], uterine artery resistance index(RI)[WMD=-0.08,95%CI(-0.11, -0.05) , P <0.00001], pregnancy rate [RR=2.18,95%CI(1.55, 3.05), P <0.00001], TCM syndrome score[WMD=-6.97,95%CI(-8.97, -4.97) , P <0.00001], effective rate [RR=1.25, 95%CI (1.13, 1.37), P < 0.00001]. Conclusion: Compared with clomiphene alone, Bushen Recipe combined with clomiphene can effectively increase the thickness of endometrium and improve the type of endometrium, promote the blood perfusion of endometrium, improve the pregnancy rate, improve the clinical symptoms, reduce the TCM syndrome score, improve the total efficiency of treatment, with high clinical application value.

Magnetic resonance imaging-based radiomics model for preoperative assessment of risk stratification in endometrial cancer

BACKGROUND Preoperative risk stratification is significant for the management of endometrial cancer(EC)patients.Radiomics based on magnetic resonance imaging(MRI)in combination with clinical features may be useful to predict the risk grade of EC.AIM To construct machine learning models to predict preoperative risk stratification of patients with EC based on radiomics features extracted from MRI.METHODS The study comprised 112 EC patients.The participants were randomly separated into training and validation groups with a 7:3 ratio.Logistic regression analysis was applied to uncover independent clinical predictors.These predictors were then used to create a clinical nomogram.Extracted radiomics features from the T2-weighted imaging and diffusion weighted imaging sequences of MRI images,the Mann-Whitney U test,Pearson test,and least absolute shrinkage and selection operator analysis were employed to evaluate the relevant radiomic features,which were subsequently utilized to generate a radiomic signature.Seven machine learning strategies were used to construct radiomic models that relied on the screening features.The logistic regression method was used to construct a composite nomogram that incorporated both the radiomic signature and clinical independent risk indicators.RESULTS Having an accuracy of 0.82 along with an area under the curve(AUC)of 0.915[95%confidence interval(CI):0.806-0.986],the random forest method trained on radiomics characteristics performed better than expected.The predictive accuracy of radiomics prediction models surpassed that of both the clinical nomogram(AUC:0.75,95%CI:0.611-0.899)and the combined nomogram(AUC:0.869,95%CI:0.702-0.986)that integrated clinical parameters and radiomic signature.CONCLUSION The MRI-based radiomics model may be an effective tool for preoperative risk grade prediction in EC patients.

circRNA3669 promotes goat endometrial epithelial cells proliferation via miR-26a/RCN2 to activate PI3K/AKT-mTOR and MAPK pathways

The development of receptive endometrium(RE) from pre-receptive endometrium(PE) for successful embryo implantation is a complex dynamic process in which the morphology and physiological states of the endometrial epithelium undergo a series of significant changes, including cell proliferation and apoptosis. However, the molecular mechanisms are not yet fully understood. In this study, a higher circRNA3669 level was observed in PE than in RE of goats. Functional assays revealed that this overexpression promoted the proliferation of goat endometrial epithelial cells(GEECs) by activating the expression of genes related to the PI3K/AKT-mTOR and MAPK pathways,thereby inhibiting apoptosis in vitro. Furthermore, circRNA3669 functioned as a competing endogenous RNA(ceRNA) to upregulate Reticulocalbin-2(RCN2) expression at the post-transcriptional level by interacting with and downregulating miR-26a in GEECs. In addition, RCN2, which is highly expressed in the PE of goats, was found to be regulated by β-estradiol(E2) and progesterone(P4). Our results demonstrated that RCN2 also affected the key proteins PI3K, AKT, mTOR, JNK, and P38 in the PI3K/AKT-mTOR and MAPK pathways, thereby facilitating GEECs proliferation and suppressing their apoptosis in vitro. Collectively, we constructed a new circRNA3669-miR-26aRCN2 regulatory network in GEECs, which further provides strong evidence that circRNA could potentially play a crucial regulatory role in the development of RE in goats.

Antitumor Effect of Apcin on Endometrial Carcinoma via p21-Mediated Cell Cycle Arrest and Apoptosis

Objective Endometrial carcinoma(EC)is a prevalent gynecological malignancy characterized by increasing incidence and mortality rates.This underscores the critical need for novel therapeutic targets.One such potential target is cell division cycle 20(CDC20),which has been implicated in oncogenesis.This study investigated the effect of the CDC20 inhibitor Apcin on EC and elucidated the underlying mechanism involved.Methods The effects of Apcin on EC cell proliferation,apoptosis,and the cell cycle were evaluated using CCK8 assays and flow cytometry.RNA sequencing(RNA-seq)was subsequently conducted to explore the underlying molecular mechanism,and Western blotting and coimmunoprecipitation were subsequently performed to validate the results.Animal studies were performed to evaluate the antitumor effects in vivo.Bioinformatics analysis was also conducted to identify CDC20 as a potential therapeutic target in EC.Results Treatment with Apcin inhibited proliferation and induced apoptosis in EC cells,resulting in cell cycle arrest.Pathways associated with apoptosis and the cell cycle were activated following treatment with Apcin.Notably,Apcin treatment led to the upregulation of the cell cycle regulator p21,which was verified to interact with CDC20 and consequently decrease the expression of downstream cyclins in EC cells.In vivo experiments confirmed that Apcin treatment significantly impeded tumor growth.Higher CDC20 expression was observed in EC tissue than in nonmalignant tissue,and increased CDC20 expression in EC patients was associated with shorter overall survival and progress free interval.Conclusion CDC20 is a novel molecular target in EC,and Apcin could be developed as a candidate antitumor drug for EC treatment.

Development and validation of a circulating tumor DNA-based optimization-prediction model for short-term postoperative recurrence of endometrial cancer

BACKGROUND Endometrial cancer(EC)is a common gynecological malignancy that typically requires prompt surgical intervention;however,the advantage of surgical management is limited by the high postoperative recurrence rates and adverse outcomes.Previous studies have highlighted the prognostic potential of circulating tumor DNA(ctDNA)monitoring for minimal residual disease in patients with EC.AIM To develop and validate an optimized ctDNA-based model for predicting shortterm postoperative EC recurrence.METHODS We retrospectively analyzed 294 EC patients treated surgically from 2015-2019 to devise a short-term recurrence prediction model,which was validated on 143 EC patients operated between 2020 and 2021.Prognostic factors were identified using univariate Cox,Lasso,and multivariate Cox regressions.A nomogram was created to predict the 1,1.5,and 2-year recurrence-free survival(RFS).Model performance was assessed via receiver operating characteristic(ROC),calibration,and decision curve analyses(DCA),leading to a recurrence risk stratification system.RESULTS Based on the regression analysis and the nomogram created,patients with postoperative ctDNA-negativity,postoperative carcinoembryonic antigen 125(CA125)levels of<19 U/mL,and grade G1 tumors had improved RFS after surgery.The nomogram’s efficacy for recurrence prediction was confirmed through ROC analysis,calibration curves,and DCA methods,highlighting its high accuracy and clinical utility.Furthermore,using the nomogram,the patients were successfully classified into three risk subgroups.CONCLUSION The nomogram accurately predicted RFS after EC surgery at 1,1.5,and 2 years.This model will help clinicians personalize treatments,stratify risks,and enhance clinical outcomes for patients with EC.

Megestrol acetate plus metformin for fertility-sparing treatment of atypical endometrial hyperplasia and early-stage endometrial adenocarcinoma: a prospective study

Objective To evaluate the efficacy of medroxyprogesterone acetate(MA)plus metformin as the primary fertility-sparing treatment for atypical endometrial hyperplasia(AEH)and early-stage grade 1 endometrial adenocarcinoma(G1 EAC)and the recurrence rate after treatment.Methods Sixty patients(aged 20-42 years)with AEH and/or grade 1 EAC limited to the endometrium were enrolled prospectively and randomized into two groups(n=30)to receive oral MA treatment at the daily dose of 160 mg(control)or MA plus oral metformin(850 mg,twice a day)for at least 6 months.The treatment could extend to 12 months until a complete response(CR)was achieved,and follow-up hysteroscopy and curettage were performed every 3 months.For all the patients who achieved CR,endometrial expressions of IGFBP-rP1,p-Akt and p-AMPK were detected immunohistochemically.Results A total of 58 patients completed the treatment.After 9 months of treatment,23(76.7%)patients in the combined treatment group and 20(71.4%)in the control group achieved CR;two patients in the control group achieved CR after converting to the combined treatment.The recurrence rate did not differ significantly between the control group and combined treatment group(30.0%vs 22.7%,P>0.05).Ten(35.7%)patients in the control group experienced significant weight gain of 5.7±6.1 kg,while none of the patients receiving the combined treatment exhibited significant body weight changes.Compared with the control group,the patients receiving the combined treatment showed enhanced endometrial expressions of IGFBP-rP1 and p-AMPK with lowered p-Akt expression.Conclusion Metformin combined with MA may provide an effective option for fertility-sparing treatment of AEH and grade 1 stage IA EAC,and the clinical benefits of metformin for controlling MA-induced weight gain and promoting endometrial expressions of IGFBP-rP1 and p-AMPK while inhibiting p-Akt expression warrants further study.

Decoding exercise-induced atomic components and prognostic shifts in endometrial carcinoma through differentially expressed genes

Background:This study aimed to portray the atomic intelligence and prognostic implications of differentially expressed genes and their involvement in biological pathways in endometrial carcinoma,with a specific focus on the impacts of exercise on cancer.Methods:We utilized a multi-faceted approach,including volcano plots,Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses,Venn diagrams,protein-protein interaction networks,Kaplan-Meier survival analysis,Gene Set Variety Analysis,and single-cell transcriptomic analysis.Furthermore,we profiled tumor mutational scenes,assessed the prognostic value of immune-related features,and conducted a comprehensive examination of genetic variations and their impact on tumor mutational burden across different cancer types.Multidimensional genomic interactions and methylation elements were also investigated.Using real-time quantitative PCR and immunofluorescence staining,the effects of B-cell lymphoma 2(BCL2)silencing on TNF-αand caspase-3 gene expression were evaluated.Results:Our study identified a noteworthy number of differentially expressed genes in endometrial carcinoma with potential links to athletic performance traits.BCL2 expression levels were found to be associated with survival outcomes,and its changeability across cancers was related to immune cell infiltration and immune checkpoint gene expression.Single-cell investigations uncovered cellular complexity within tumor microenvironments and critical biological pathways in BCL2-overexpressing cells.The expression flow and mutational effect of BCL2 in endometrial carcinoma were characterized,and the prognostic implications of immune-related features were assessed.Hereditary variations,including copy number variations and their relationship with gene expression and tumor mutational burden,were investigated.Multidimensional genomic transaction highlighted the essential role of regulatory genes in cancer pathogenesis.Silencing of the BCL2 gene significantly inhibited the proliferation of HEC-108 cells and promoted apoptosis,as evidenced by decreased TNF-αgene expression and increased caspase-3 gene expression.Immunofluorescence staining further confirmed these results.Conclusion:This study gives a point-by-point understanding of the atomic intelligence and prognostic implications in endometrial carcinoma and across various other cancers.BCL2’s role as a modulatory factor within the tumor-resistant environment and its potential impact on disease prognosis and response to immunotherapy were underscored.The multidimensional genomic analysis provides insights into the complex interaction between genetic and epigenetic variables in cancer,which may shed light on future therapeutic strategies.This study indicates that silencing the BCL2 gene can significantly inhibit tumor cell proliferation and promote apoptosis through the regulation of the TNF-αand caspase-3 pathways.

ZNF554 Inhibits Endometrial Cancer Progression via Regulating RBM5 and Inactivating WNT/β-Catenin Signaling Pathway

Objective:Uterine corpus endometrial carcinoma(UCEC),a kind of gynecologic malignancy,poses a significant risk to women’s health.The precise mechanism underlying the development of UCEC remains elusive.Zinc finger protein 554(ZNF554),a member of the Krüppel-associated box domain zinc finger protein superfamily,was reported to be dysregulated in various illnesses,including malignant tumors.This study aimed to examine the involvement of ZNF554 in the development of UCEC.Methods:The expression of ZNF554 in UCEC tissues and cell lines were examined by qRT-PCR and Western blot assay.Cells with stably overexpressed or knocked-down ZNF554 were established through lentivirus infection.CCK-8,wound healing,and Transwell invasion assays were employed to assess cell proliferation,migration,and invasion.Propidium iodide(PI)staining combined with fluorescence-activated cell sorting(FACS)flow cytometer was utilized to detect cell cycle distribution.qRT-PCR and Western blotting were conducted to examine relative mRNA and protein levels.Chromatin immunoprecipitation assay and luciferase reporter assay were used to explore the regulatory role of ZNF554 in RNA binding motif 5(RBM5).Results:The expression of ZNF554 was found to be reduced in both UCEC samples and cell lines.Decreased expression of ZNF554 was associated with higher tumor stage,decreased overall survival,and reduced disease-free survival in UCEC.ZNF554 overexpression suppressed cell proliferation,migration,and invasion,while also inducing cell cycle arrest.In contrast,a decrease in ZNF554 expression resulted in the opposite effect.Mechanistically,ZNF554 transcriptionally regulated RBM5,leading to the deactivation of the Wingless(WNT)/β-catenin signaling pathway.Moreover,the findings from rescue studies demonstrated that the inhibition of RBM5 negated the impact of ZNF554 overexpression onβ-catenin and p-glycogen synthase kinase-3β(p-GSK-3β).Similarly,the deliberate activation of RBM5 reduced the increase inβ-catenin and p-GSK-3βcaused by the suppression of ZNF554.In vitro experiments showed that ZNF554 overexpression-induced decreases in cell proliferation and migration were counteracted by RBM5 knockdown.Additionally,when RBM5 was overexpressed,it hindered the improvements in cell proliferation and migration caused by reducing the ZNF554 levels.Conclusion:ZNF554 functions as a tumor suppressor in UCEC.Furthermore,ZNF554 regulates UCEC progression through the RBM5/WNT/β-catenin signaling pathway.ZNF554 shows a promise as both a prognostic biomarker and a therapeutic target for UCEC.

Endometrial carcinoma with cervical stromal invasion:Three case reports

BACKGROUND Endometrial cancer is a kind of well-known tumors of female genitourinary system.Cervical stromal invasion is an adverse factor for poor prognosis of endometrial cancer.There is still controversy regarding the use of magnetic resonance imaging(MRI)in the diagnosis of cervical stromal invasion of endometrial cancer.The diagnosis of cervical stromal invasion varies significantly between different observers and institutions.We present a limited case series of the particular pattern of endometrial cancer,which infiltrates the cervical stroma and is often overlooked.CASE SUMMARY We present three cases of endometrial carcinoma with cervical stromal invasion with cancer-free uterine cavity.One patient,a reproductive-aged woman,exhibited irregular menstruation and was diagnosed with endometrial polyps by hysteroscopy and segmental curettage.A MRI scan revealed polypoid nodules within the internal cervical orifice.The other two cases were postmenopausal women who presented with abnormal vaginal bleeding.Hysteroscopy and segmental curettage suggested atypical hyperplasia of the endometrium.MRI scans did not detect any malignant signs in the endometrium.In one case,a nonthickened endometrium was observed,while in another,hyperplasia of the endometrium was seen.Notably,none of these patients had malignant tumors identified in the uterine cavity via MRI scans.However,postoperative pathological results following hysterectomy consistently indicated cervical stromal invasion.CONCLUSION Cervical stromal invasion is easily missed if no cancer is found in the uterine body on MRI.Immunohistochemistry of endoscopic curettage specimens should be conducted to avoid underestimation of the disease.

Mifepristone as luteal phase endometrial contraceptive

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Effect of Estrogen and Antiestrogen on Chemotherapeutic Sensitivity of Endometrial Carcinoma Cell Line

Objective: To study the effect of estrogen and tamoxifen on chemotherapeutic sensitivity in ER(+) endometrial carcinoma cells.Methods: DNA fragmentation as the criteria for apoptotic cell death was used to evaluate the value of estrogen, tamoxifen and adriamycin in ER(+) endometrial carcinoma cells. DNA fragmentation was measured with the cell death ELISA.Results: Adriamycin and tamoxifen could induce apoptosis in ER(+) endometrial carcinoma cell. The cell apoptosis level was decreased with the increasing of 17-β-estradiol concentration (P<0.001) and was inversely proportional to 17-β-estradiol concentration (IgM) (P<0.01). The cell apoptosis level was increased with the increasing of tamoxifen concentration (P<0.01) and was also directly proportional to tamoxifen concentration (IgM). Furthermore, the cell apoptosis level was increased significantly after treated with both tamoxifen and adriamycin.Conclusion: Estrogen may block apoptosis induced by adriamycin in ER(+) endometrial carcinoma cell. Tamoxifen can increase the sensitivity of endometrial carcinoma cell to adriamycin. Tamoxifen combined with chemotherapeutic drug may be of significant therapeutic benefit in ER(+) endometrial carcinoma. Key words endometrial carcinoma - estrogen - tamoxifen - adriamycin - cell apoptosis

Analyses of circRNA profiling during the development from pre-receptive to receptive phases in the goat endometrium

Background: Recent studies have revealed that noncoding RNAs play important regulatory roles in the formation of endometrial receptivity.Circular RNAs(circRNAs) are a universally expressed noncoding RNA species that have been recently proposed to act as miRNA sponges that directly regulate expression of target genes or parental genes.Results: We used Illumina Solexa technology to analyze the expression profiles of circRNAs in the endometrium from three goats at gestational day 5(pre-receptive endometrium,PE) and three goats at gestational day 15(receptive endometrium,RE).Overall,21,813 circRNAs were identified,of which 5,925 circRNAs were specific to the RE and 9,078 were specific to the PE,which suggested high stage-specificity.Further analysis found 334 differentially expressed circRNAs in the RE compared with PE(P < 0.05).The analysis of the circRNA-miRNA interaction network further supported the idea that circRNAs act as miRNA sponges to regulate gene expression.Moreover,some circRNAs were regulated by estrogen(E2)/progesterone(P4) in endometrial epithelium cell lines(EECs) and endometrial stromal cell line(ESCs),and each circRNA molecule exhibited unique regulation characteristics with respect to E2 and P4.Conclusions: These data provide an endometrium circRNA expression atlas corresponding to the biology of the goat receptive endometrium during embryo implantation.