Endometrial cancer is the most common gynecologic cancer diagnosed in the United States and mortality is on the rise.Advanced and recurrent endometrial cancer represents a treatment challenge as historically there hav...Endometrial cancer is the most common gynecologic cancer diagnosed in the United States and mortality is on the rise.Advanced and recurrent endometrial cancer represents a treatment challenge as historically there have been limited therapeutic options for patients.In the last several years,multiple practice-changing clinical trials have led to significant improvements in the treatment landscape.This review will cover updates in the treatment and management of advanced and recurrent endometrial cancer with a focus on novel therapeutics,such as anti-PD-L1 and PD-1 inhibitors,poly ADP-ribose polymerase(PARP)inhibitors,antibody-drug conjugates,and hormonal therapy.展开更多
As of 2023, endometrial cancer (EC) ranks second among malignant tumors of the female reproductive system in China, following cervical cancer, posing a significant burden on the country’s healthcare system. Postmenop...As of 2023, endometrial cancer (EC) ranks second among malignant tumors of the female reproductive system in China, following cervical cancer, posing a significant burden on the country’s healthcare system. Postmenopausal asymptomatic endometrial thickening is primarily benign, often involving endometrial polyps. However, previous clinical studies indicate a relatively high malignancy rate for postmenopausal endometrial polyps, suggesting the necessity for active intervention, particularly in cases with high-risk factors for EC. This article reviews the research progress on risk factors for endometrial lesions in postmenopausal patients with asymptomatic endometrial thickening, aiming to provide insights for clinical diagnosis and treatment.展开更多
Objective:Endometrial tuberculosis,which commonly affects women of reproductive age,is a significant cause of intrauterine adhesions(IUA),potentially leading to hypomenorrhea,amenorrhea,and infertility.Hysteroscopic a...Objective:Endometrial tuberculosis,which commonly affects women of reproductive age,is a significant cause of intrauterine adhesions(IUA),potentially leading to hypomenorrhea,amenorrhea,and infertility.Hysteroscopic adhesiolysis is the primary treatment for IUA;however,studies specifically addressing its efficacy in tuberculosisinduced IUA remain scarce.This study aims to evaluate the therapeutic outcomes of hysteroscopic adhesiolysis for IUA caused by endometrial tuberculosis.Methods:This retrospective cohort study included patients diagnosed with tuberculosisinduced IUA who underwent hysteroscopic adhesiolysis at the Third Xiangya Hospital of Central South University between May 2014 and October 2022.Clinical data including age,medical history,adhesion severity,surgical treatment,and reproductive outcomes were analyzed.Results:Among 39 patients identified,2 were lost to follow-up.A total of 37 patients were included,with a follow-up duration ranging from 6 months to 9 years.Hypomenorrhea was reported in 24(64.9%)patients,secondary amenorrhea in 10(27.0%)patients,and normal menstruation in 3(8.1%)patients.Most patients presented with primary infertility(59.5%),and only 2(5.4%)had secondary infertility.The median American Fertility Society(AFS)score at initial assessment was 10(range,8−12);8(21.6%)patients had moderate IUA,and 29(78.4%)had severe IUA.A total of 86 surgical procedures were performed across 37 patients,with 27 patients undergoing 2 or more surgeries.Postoperatively,25(67.6%)patients achieved normalization of the uterine cavity,while 12(32.4%)still had a reduced cavity.Only 7(18.9%)patients had a grossly normal endometrium at the final surgery,all of whom had moderate adhesions at the initial procedure.Menstrual flow returned to normal in 12(32.4%)patients,while 25(67.6%)continued to experience hypomenorrhea.Of 29 patients who attempted in vitro fertilization and embryo transfer(IVF-ET),only 6(20.7%)conceived.Among these,4(13.8%)delivered at term via cesarean section;one case was complicated by postpartum hemorrhage due to uterine atony and another by placental adhesion.Conclusion:Endometrial tuberculosis can lead to severe IUA.Hysteroscopic adhesiolysis facilitates cavity restoration and improvement of menstrual conditions,but the overall reproductive outcomes remain suboptimal.展开更多
Background Increased backfat thickness of sows in early gestation is negative to reproductive performance.Endometrial receptivity is an important determinant of reproductive success,but it is unclear whether the effec...Background Increased backfat thickness of sows in early gestation is negative to reproductive performance.Endometrial receptivity is an important determinant of reproductive success,but it is unclear whether the effect of sow backfat thickness on litter size is associated with endometrial receptivity and whether melatonin treatment may have benefits.The present study seeks to answer these questions through in vitro and in vivo investigations.Results Excessive lipid deposition and lower melatonin levels in the uterus are detrimental to endometrial receptivity and embryo implantation in high backfat thickness sows.In cells treated with melatonin,the MT2/PI3K/LIF axis played a role in reducing lipid accumulation in porcine endometrial epithelium cells and improved endometrial receptivity.Furthermore,we found a reduction of lipids in the uterus after eight weeks of intraperitoneal administration of melatonin to HFD mice.Notably,melatonin treatment caused a significant reduction in the deposition of endometrial collagen,an increase in the number of glands,and repair of the pinopode structure,ultimately improving endometrial receptivity,promoting embryo implantation,and increasing the number of litter size of mice.Conclusions Collectively,the finding reveals the harmful effects of high backfat thickness sows on embryo implantation and highlight the role of melatonin and the MT2/PI3K/LIF axis in improving endometrial receptivity by enhancing metabolism and reducing the levels of uterine lipids in obese animals.展开更多
Objective:To construct a pH-responsive paclitaxel(PTX)-exosome composite nanocarrier and investigate its inhibitory effect on the proliferation of endometrial cancer cells(HEC-1A).Methods:PTX was loaded into exosomes ...Objective:To construct a pH-responsive paclitaxel(PTX)-exosome composite nanocarrier and investigate its inhibitory effect on the proliferation of endometrial cancer cells(HEC-1A).Methods:PTX was loaded into exosomes derived from adipose mesenchymal stem cells using the thin-film hydration method,and modified with polyethylene glycol-polylactic-co-glycolic acid(PEG-PLGA)to form nanocarriers(PTX-Exo-NPs).The particle size and morphology were detected by nanoparticle size and Zeta potential analyzer;drug encapsulation efficiency and drug loading capacity were determined by high-performance liquid chromatography;drug release behavior was evaluated in vitro under simulated acidic(pH 5.5)and physiological(pH 7.4)conditions;MTT assay and flow cytometry were used to detect the effects of the carrier on the proliferation,apoptosis,and cell cycle distribution of HEC-1A cells.Results:PTX-Exo-NPs exhibited a uniform spherical shape with a particle size of(128.5±5.2)nm,PTX encapsulation efficiency of 92.3%±2.1%,and drug loading capacity of 15.6%±0.8%.Drug release rate in the acidic environment(85.3%±2.1%within 72 h)was significantly higher than that in the physiological environment(48.0%±1.7%).In vitro experiments demonstrated that the proliferation inhibition rate of PTX-Exo-NPs on HEC-1A cells was higher than that of free PTX,with a lower IC50(0.64μM vs 4.70μM),and could induce cell apoptosis(apoptosis rate:28.7%±2.1%vs 14.2%±1.5%)and promote cell cycle arrest(G_2/M rate:45.3%±3.2%).Conclusion:PTX-Exo-NPs exhibit pH-responsive characteristics,which can target drug release through the acidic microenvironment,enhance the proliferation inhibition and pro-apoptotic effect on endometrial cancer cells,thus serving as a potential strategy for targeted therapy of endometrial tumors.展开更多
BACKGROUND Endometrial peristalsis(EmP)has been considered as a new indicator for eva-luating endometrial receptivity and is associated with embryo implantation rate and successful pregnancy rate.However,EmP remains u...BACKGROUND Endometrial peristalsis(EmP)has been considered as a new indicator for eva-luating endometrial receptivity and is associated with embryo implantation rate and successful pregnancy rate.However,EmP remains understudied,incon-sistently measured,and poorly understood.New methods are needed urgently for better clinical practice.AIM To explore the value of EmP analysis(EmPA)technique in detecting and analy-zing EmP features automatically and quantitatively.METHODS One hundred and forty-five patients without abnormal findings on conventional transvaginal ultrasound were included in this study.A mid sagittal plane of ute-rus was recorded for 2 minutes in each patient and EmP features were analyzed using EmPA technique.EmP features in 50 patients were also analyzed by naked eyes analysis and the results of two methods were compared.RESULTS EmPA was unsuccessful in 9 patients(9/145,6.21%)due to the interference of respiratory or intestinal movement and was successful in 136 patients(136/145,93.79%),of whom 21 patients showed no EmP and 115 patients underwent EmPA and obtained quantitative results.The results of EmPA technique and naked eyes analysis about EmP intensity and transfer time had no significant consistence.Menstrual cycle,uterine position and history of induced abortion affected the quantitative results of EmPA.CONCLUSION EmPA technique provides noninvasive,quantitative and accurate detection and analysis of EmP in normal population and can evaluate EmP changes associated with menstrual cycle,uterine position and history of induced abortion.展开更多
Objective To evaluate the impact of endometrial polyps(EP)on postoperative pregnancy outcomes in infertile women with endometriosis(EMs).Methods PubMed,Embase,The Cochrane Library,CNKI,VIP,SinoMed,and WanFang Data dat...Objective To evaluate the impact of endometrial polyps(EP)on postoperative pregnancy outcomes in infertile women with endometriosis(EMs).Methods PubMed,Embase,The Cochrane Library,CNKI,VIP,SinoMed,and WanFang Data databases were searched to include clinical studies on the effect of EP on pregnancy outcomes in patients with EMs,published before August 31,2020.A meta-analysis was performed using Rev Man 5.3 software after two investigators independently screened the literature,extracted information,and evaluated the risk of bias of the included studies.Results The meta-analysis included ten studies(651 and 1,040 in the combined EP and uncomplicated EP groups,respectively).The spontaneous pregnancy rate,clinical pregnancy rate,and live birth rate were significantly lower in the group with combined EPs than in the group without combined EPs[Odd’s ratio(OR)=0.63,95%confidence interval(CI):0.50–0.80,P=0.0001;OR=0.63,95%CI:0.48–0.84,P=0.001;OR=0.63,95%CI:0.42–0.96,P=0.03],and the rate of embryonic abortion was significantly higher than that in the uncomplicated EP group[OR=3.10,95%CI:1.52–6.32,P=0.002].Conclusion EP may adversely affect pregnancy outcomes in patients with infertility and EMs.Even after surgical treatment,EP can still reduce natural pregnancy,clinical pregnancy,and live birth rates in infertile women with EMs and increase the risk of embryo arrest in these women.展开更多
BACKGROUND Endometrial cancer(EC)is the most common gynecological malignancy in high-income countries,with incidence rates rising globally.Early and accurate diag-nosis is essential for improving outcomes.Transvaginal...BACKGROUND Endometrial cancer(EC)is the most common gynecological malignancy in high-income countries,with incidence rates rising globally.Early and accurate diag-nosis is essential for improving outcomes.Transvaginal ultrasound(TVUS)remains a cost-effective first-line tool,and emerging techniques such as three-dimensional(3D)ultrasound(US),contrast-enhanced US(CEUS),elastography,and artificial intelligence(AI)-enhanced imaging may further improve diagnostic performance.AIM To systematically review recent advances in US-based imaging techniques for the diagnosis and staging of EC,and to compare their performance with magnetic resonance imaging(MRI).METHODS A systematic search of PubMed,Scopus,Web of Science,and Google Scholar was performed to identify studies published between January 2010 and March 2025.Eligible studies evaluated TVUS,3D-US,CEUS,elastography,or AI-enhanced US in EC diagnosis and staging.Methodological quality was assessed using the QUADAS-2 tool.Sensitivity,specificity,and area under the curve(AUC)were extracted where available,with narrative synthesis due to heterogeneity.RESULTS Forty-one studies met the inclusion criteria.TVUS demonstrated high sensitivity(76%–96%)but moderate specificity(61%–86%),while MRI achieved higher spe-cificity(84%–95%)and superior staging accuracy.3D-US yielded accuracy com-parable to MRI in selected early-stage cases.CEUS and elastography enhanced tissue characterization,and AI-enhanced US achieved pooled AUCs up to 0.91 for risk prediction and lesion segmentation.Variability in per-formance was noted across modalities due to patient demographics,equipment differences,and operator experi-ence.CONCLUSION TVUS remains a highly sensitive initial screening tool,with MRI preferred for definitive staging.3D-US,CEUS,elastography,and AI-enhanced techniques show promise as complementary or alternative approaches,particularly in low-resource settings.Standardization,multicenter validation,and integration of multi-modal imaging are needed to optimize diagnostic pathways for EC.展开更多
BACKGROUND Claudin-6(CLDN6),a tight junction protein typically restricted to embryonic tissues,is re-expressed in various cancers.However,its prognostic significance in high-grade endometrial carcinoma(HGEC)remains un...BACKGROUND Claudin-6(CLDN6),a tight junction protein typically restricted to embryonic tissues,is re-expressed in various cancers.However,its prognostic significance in high-grade endometrial carcinoma(HGEC)remains unclear.AIM To investigate the expression pattern of CLDN6 in HGEC and assess its correlation with clinicopathological parameters and patient survival.METHODS Immunohistochemical analysis of CLDN6 expression was performed on formalinfixed,paraffin-embedded tissues from 80 patients diagnosed with HGEC.Associations between CLDN6 expression and histological subtype,the International Federation of Gynecology and Obstetrics(FIGO)stage,depth of myometrial invasion,lymphovascular space invasion,recurrence,and survival outcomes were statistically analysed.Univariate and multivariate Cox regression models were used to identify independent prognostic factors.RESULTS High CLDN6 expression was detected in a subset of HGEC patients and was significantly associated with nonendometrioid histology(P=0.026),advanced FIGO stage(P=0.015),deep myometrial invasion(P=0.038),and recurrence(P=0.002).While Kaplan-Meier analysis did not reveal a statistically significant difference in disease-free survival or overall survival between the high CLDN6 expression group and the low CLDN6 expression group,multivariate Cox regression revealed that CLDN6 overexpression was an independent predictor of shorter disease-free survival[hazard ratio(HR)=68.98,P=0.022]and overall survival(HR=24.023,P=0.038).CONCLUSION CLDN6 overexpression is associated with aggressive tumor features and poor clinical outcomes in HGEC,suggesting its utility as a prognostic biomarker and potential therapeutic target.展开更多
BACKGROUND Seek highly effective treatment measures for improving mood and sleep.AIM To explore the effects of mood and depression in patients with endometrial cancer after cognitive behavioral therapy(CBT)and mindful...BACKGROUND Seek highly effective treatment measures for improving mood and sleep.AIM To explore the effects of mood and depression in patients with endometrial cancer after cognitive behavioral therapy(CBT)and mindfulness-based stress reduction.METHODS In a prospective study,90 patients with diabetes,endometrial cancer,and depression were selected from January 2023 to January 2024 in our hospital.There were 45 patients in the control group and 45 patients in the observation group.In addition to the conventional treatment,the control group received cognitive behavioral treatment,and the observation group:Control group was given to compare changes in mood state and sleep quality before and after the intervention.Follow-up was performed3 months after treatment completion.RESULTS Before treatment,the mood and sleep quality scores between the two groups(P>0.05);in the observation group,the 5 negative mood scores were lower and lower than the control group;the 2 positive mood scores were higher than in the control group,and the difference was statistically significant(P<0.05);compared with before treatment,the 7 sleep quality scores and Pittsburgh sleep quality index scale total score in the observation group and lower in the control group(P<0.05).CONCLUSION In patients with diabetes and endometrial cancer,mood state and sleep quality significantly improved after CBT and breathing relaxation.These findings provide new and effective treatment strategies in clinical practice.展开更多
Endometrial injury caused by repeated uterine procedures,infections,inflammation,or uterine artery dysfunction can deplete endometrial stem/progenitor cells and impair regeneration,thereby diminishing endometrial rece...Endometrial injury caused by repeated uterine procedures,infections,inflammation,or uterine artery dysfunction can deplete endometrial stem/progenitor cells and impair regeneration,thereby diminishing endometrial receptivity and evidently lowering the live birth,clinical pregnancy,and embryo implantation rates.Currently,safe and effective clinical treatment methods or gene-targeted therapies are unavailable,especially for severe endometrial injury.Umbilical cord mesenchymal stem cells and their extracellular vesicles are characterized by their simple collection,rapid proliferation,low immunogenicity,and tumorigenicity,along with their involvement in regulating angiogenesis,immune response,cell apoptosis and proliferation,inflammatory response,and fibrosis,Therefore,these cells and vesicles hold broad potential for application in endometrial repair.This article reviewed recent research on human umbilical cord mesenchymal stem cells as well as their extracellular vesicles in repairing endometrial injury.展开更多
Endometrial injury caused by intrauterine procedures can result in infertility and recurrent miscarriages,and the current clinical treatments are inadequate for effective endometrial repair.The implantation of anti-ad...Endometrial injury caused by intrauterine procedures can result in infertility and recurrent miscarriages,and the current clinical treatments are inadequate for effective endometrial repair.The implantation of anti-adhesion hydrogels combined with growth factors is a promising strategy to address endometrial injury.Insulin-like growth factor 1 is closely associated with endometrial growth and plays a crucial role in endometrial receptivity that is essential for fertility.However,its high cost,environmental sensitivity,and short biological half-life limit its practical applications.In this study,we developed a two-component peptide-based hydrogel consisting of a biotinylated peptide and an insulin-like growth factor 1(IGF-1)mimetic peptide,both of which were designed with self-assembly capabilities.The resultant hydrogel exhibited significant mechanical properties and retained its native IGF-1 bioactivity.In vivo experiments demonstrated that the hydrogel significantly facilitated proliferation and vascular restoration.Additionally,it effectively reduced fibrosis by decreasing collagen accumulation,restoring the expression of progesterone receptors,and enhancing endometrial receptivity,which are crucial for embryo implantation.These findings highlight the potential of the two-component peptide-based hydrogel as an innovative therapeutic approach for treating endometrial injury.展开更多
BACKGROUND The microcystic,elongated,and fragmented(MELF)pattern of invasion in endometrioid endometrial carcinoma(EEC)is a special mode of myometrial invasion that has been recently recognized by the pathology commun...BACKGROUND The microcystic,elongated,and fragmented(MELF)pattern of invasion in endometrioid endometrial carcinoma(EEC)is a special mode of myometrial invasion that has been recently recognized by the pathology community.Overex-pression of CXC chemokine receptor 4(CXCR4)in tumor cells contributes to tumor growth,invasion,angiogenesis,metastasis,and recurrence.AIM To explore the correlation between CXCR4 expression in EEC and MELF invasion and clinicopathological features.METHODS A total of 205 EEC patients treated at Peking University People’s Hospital from June 2020 to December 2021 were selected(60 cases with MELF invasion,145 cases without).The clinicopathological features of the two groups were compared,and expression of CXCR4 protein,estrogen receptor,and progesterone receptor was detected and compared by immunohistochemistry.RESULTS EEC with MELF invasion was significantly associated with low tumor grade,lymphovascular space invasion,deep myometrial invasion,cervical stromal involvement,and lymph node metastasis.There was a difference in CXCR4 expression between the two groups,with the MELF group having a significantly higher expression than the non-MELF group.CONCLUSION CXCR4 expression is significantly increased in EEC with MELF invasion and in the MELF invasion area,which may promote tumor invasion and metastasis and has some value for prognostic assessment.展开更多
This article comments on the study by Zhang et al,which proposed that exosomes derived from hypoxia-injured endometrial epithelial cells promote human umbilical cord mesenchymal stem cell migration and differentiation...This article comments on the study by Zhang et al,which proposed that exosomes derived from hypoxia-injured endometrial epithelial cells promote human umbilical cord mesenchymal stem cell migration and differentiation into endo-metrial epithelial cells via exosomal miR-137-3p.The authors demonstrated that miR-137-3p targets ubiquitin protein ligase E3C and activates signal transducer and activator of transcription 3 signaling,thereby driving epithelial lineage transition.While this study expands our understanding of exosome-mediated intercellular communication in endometrial repair,several key gaps remain.Notably,microRNA(miRNA)profiling was performed in human umbilical cord mesenchymal stem cells post-exosome treatment,not in the exosomes derived from hypoxia-injured endometrial epithelial cell themselves,leaving open whether miR-137-3p is directly transferred or indirectly induced.In addition,data on exosome characterization were unavailable,and the rationale for selecting miR-137-3p over other differentially expressed miRNAs was not well justified.Future studies should include direct exosomal miRNA content analysis,in vivo validation,and deeper mechanistic exploration of the ubiquitin protein ligase E3C-signal transducer and activator of transcription 3 ubiquitination axis to establish the clinical and biological relevance of this pathway.展开更多
Endometrial thickness plays an important role in successful embryo implantation and normal pregnancy achievement.However,a thin endometrial layer(≤7 mm)may have a significant effect on microenvironment tolerance,whic...Endometrial thickness plays an important role in successful embryo implantation and normal pregnancy achievement.However,a thin endometrial layer(≤7 mm)may have a significant effect on microenvironment tolerance,which is further related to successful embryo implantation or conception,either naturally or after assisted reproductive technology.Moreover,this microenvironment tolerance shift induces hypoxic damage to endometrial epithelial cells(EECs),which results in altered signaling biomolecule secretion,including exosome content.In the context of endometrium regeneration,mesenchymal stromal cells(MSCs)and umbilical cord(UC)-derived stem cells have been applied in clinical trials with promising results.It has been recently shown that exosomes derived from hypoxic damaged EECs directly contribute to the increased migratory and regenerative abilities of UCs and MSCs.Specifically,microRNAs in exosomes secreted by the hypoxic damaged EECs,such as miR-214-5p and miR-21-5p,play a crucial role in the migratory capacity and differentiation ability of MSCs to EECs mediated through the signal transducer and activator of transcription 3(STAT3)signaling pathway.Taking into consideration the above information,UC-MSCs may be considered as a modern intervention for endometrial regeneration.展开更多
This study by Zhang et al elucidates the role of exosome miR-137-3p targeting ubiquitin protein ligase E3C to activate signal transducer and activator of transcription 3 under hypoxia conditions,thereby promoting the ...This study by Zhang et al elucidates the role of exosome miR-137-3p targeting ubiquitin protein ligase E3C to activate signal transducer and activator of transcription 3 under hypoxia conditions,thereby promoting the migration and differentiation of human umbilical cord mesenchymal stem cells to endometrial epithelial cells.It emphasizes that exosomal miR-137-3p/ubiquitin protein ligase E3C/signal transducer and activator of transcription 3 axis is a promising pathway for endometrial regeneration.This article introduced the therapeutic potential of exosomal microRNAs in regenerative medicine while underscoring the need for standardized protocols in optimizing exosome delivery and validating molecular pathways for clinical translation.展开更多
Exosomes derived from hypoxic endometrial epithelial cells are pivotal in cellular communication and tissue repair,offering new perspectives on reproductive health.This manuscript highlights the study by Zhang et al,w...Exosomes derived from hypoxic endometrial epithelial cells are pivotal in cellular communication and tissue repair,offering new perspectives on reproductive health.This manuscript highlights the study by Zhang et al,which investigates the effects of miR-214-5p and miR-21-5p in hypoxic cell-derived exosomes on human umbilical cord mesenchymal stem cells.The study reveals that low levels of these microRNAs activate the signal transducer and activator of transcription 3 signaling pathway,enhancing human umbilical cord mesenchymal stem cell migration and differentiation.These findings provide novel insights into therapeutic strategies for improving endometrial health and addressing infertility linked to thin endometrium.展开更多
BACKGROUND Thin endometrium,leading cause of recurrent implantation failure and infertility,has been found to respond to exosomes.AIM To investigate the efficacy of exosomes in addressing the issue of thin endometrium...BACKGROUND Thin endometrium,leading cause of recurrent implantation failure and infertility,has been found to respond to exosomes.AIM To investigate the efficacy of exosomes in addressing the issue of thin endometrium.METHODS RNA sequencing and reverse transcription-quantitative polymerase chain reaction were employed to identify differentially expressed microRNAs(miRNAs)in human umbilical cord mesenchymal stem cell(hucMSC)treated with exosomes enriched with endometrial cell-derived components.Additionally,Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were conducted to highlight significant enrichment in specific biological pathways,molecular functions,and cellular components.Transwell and wound healing assays were performed to assess migratory potential,and western blotting was detected protein level.RESULTS A total of 53 differentially expressed miRNAs were identified in hucMSC treated with exosomes enriched with endometrial cell-derived components,comprising 27 upregulated and 26 downregulated miRNAs,which includes miR-137-3p.Enhanced migratory potential was observed in the Transwell and wound healing assays,and western blotting confirmed the epithelial differentiation of hucMSC and the increased p-signal transducer and activator of transcription 3.These effects were attributed to the upregulation of miR-137-3p.CONCLUSION miR-137-3p in exosomes from hypoxia-affected endometrial epithelial cell stimulates the signal transducer and activator of transcription 3 signaling pathway,enhancing the migration and differentiation of hucMSC into endometrial epithelial cell.展开更多
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 epith...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.展开更多
Tetrabromobisphenol A(TBBPA)and its derivatives widely exist in various environments and biota.Although the available data indicate that TBBPA exposure is highly associated with the increased incidence of endometrial ...Tetrabromobisphenol A(TBBPA)and its derivatives widely exist in various environments and biota.Although the available data indicate that TBBPA exposure is highly associated with the increased incidence of endometrial cancer(EC),the effects of TBBPA and its main derivatives on EC proliferation and the involved crucial mechanism remain unclear.The present study aimed to investigate the effects of TBBPA and its derivatives under environmental concentrations on the proliferation of EC,and the crucial mechanism on the progression of EC caused by bromine fame retardants exposure.In this research,TBBPA and two of the most common TBBPA derivatives including TBBPA bis(2-hydroxyethyl ether)(TBBPABHEE)and TBBPA bis(dibromopropyl ether)(TBBPA-BDBPE)were screened for their capacities in induced EC proliferation and explored the related mechanism by in vitro cell culture model and in vivo mice model.Under environmental concentrations,TBBPA promoted the proliferation of EC,the main derivatives of TBBPA(TBBPA-BHEE and TBBPA-BDBPE)did not present the similar facilitation effects.The ubiquitination degradation of p53 was crucial in TBBPA induced EC proliferation,which resulted in the increase of downstream cell cycle and decrease of apoptosis.The further molecular docking result suggested the high affinity between TBBPA and ubiquitinated proteasome.This finding revealed the effects of TBBPA and its derivatives on EC proliferation,thus providing novel insights into the underlying mechanisms of TBBPA-caused EC.展开更多
文摘Endometrial cancer is the most common gynecologic cancer diagnosed in the United States and mortality is on the rise.Advanced and recurrent endometrial cancer represents a treatment challenge as historically there have been limited therapeutic options for patients.In the last several years,multiple practice-changing clinical trials have led to significant improvements in the treatment landscape.This review will cover updates in the treatment and management of advanced and recurrent endometrial cancer with a focus on novel therapeutics,such as anti-PD-L1 and PD-1 inhibitors,poly ADP-ribose polymerase(PARP)inhibitors,antibody-drug conjugates,and hormonal therapy.
文摘As of 2023, endometrial cancer (EC) ranks second among malignant tumors of the female reproductive system in China, following cervical cancer, posing a significant burden on the country’s healthcare system. Postmenopausal asymptomatic endometrial thickening is primarily benign, often involving endometrial polyps. However, previous clinical studies indicate a relatively high malignancy rate for postmenopausal endometrial polyps, suggesting the necessity for active intervention, particularly in cases with high-risk factors for EC. This article reviews the research progress on risk factors for endometrial lesions in postmenopausal patients with asymptomatic endometrial thickening, aiming to provide insights for clinical diagnosis and treatment.
基金supported by the Wisdom Accumulation and Talent Cultivation Project of Third Xiangya Hosipital of Central South University,China(YX202112).
文摘Objective:Endometrial tuberculosis,which commonly affects women of reproductive age,is a significant cause of intrauterine adhesions(IUA),potentially leading to hypomenorrhea,amenorrhea,and infertility.Hysteroscopic adhesiolysis is the primary treatment for IUA;however,studies specifically addressing its efficacy in tuberculosisinduced IUA remain scarce.This study aims to evaluate the therapeutic outcomes of hysteroscopic adhesiolysis for IUA caused by endometrial tuberculosis.Methods:This retrospective cohort study included patients diagnosed with tuberculosisinduced IUA who underwent hysteroscopic adhesiolysis at the Third Xiangya Hospital of Central South University between May 2014 and October 2022.Clinical data including age,medical history,adhesion severity,surgical treatment,and reproductive outcomes were analyzed.Results:Among 39 patients identified,2 were lost to follow-up.A total of 37 patients were included,with a follow-up duration ranging from 6 months to 9 years.Hypomenorrhea was reported in 24(64.9%)patients,secondary amenorrhea in 10(27.0%)patients,and normal menstruation in 3(8.1%)patients.Most patients presented with primary infertility(59.5%),and only 2(5.4%)had secondary infertility.The median American Fertility Society(AFS)score at initial assessment was 10(range,8−12);8(21.6%)patients had moderate IUA,and 29(78.4%)had severe IUA.A total of 86 surgical procedures were performed across 37 patients,with 27 patients undergoing 2 or more surgeries.Postoperatively,25(67.6%)patients achieved normalization of the uterine cavity,while 12(32.4%)still had a reduced cavity.Only 7(18.9%)patients had a grossly normal endometrium at the final surgery,all of whom had moderate adhesions at the initial procedure.Menstrual flow returned to normal in 12(32.4%)patients,while 25(67.6%)continued to experience hypomenorrhea.Of 29 patients who attempted in vitro fertilization and embryo transfer(IVF-ET),only 6(20.7%)conceived.Among these,4(13.8%)delivered at term via cesarean section;one case was complicated by postpartum hemorrhage due to uterine atony and another by placental adhesion.Conclusion:Endometrial tuberculosis can lead to severe IUA.Hysteroscopic adhesiolysis facilitates cavity restoration and improvement of menstrual conditions,but the overall reproductive outcomes remain suboptimal.
基金supported by the China Agriculture Research System(CARS-35-PIG)the National Natural Science Foundation of China(32272847,U22A20516)+1 种基金the National Key Research and Development Program of China(No.2021YFF1000602)the Key Research and Development Program of Shaanxi Province(No.2022ZDLNY01–04)。
文摘Background Increased backfat thickness of sows in early gestation is negative to reproductive performance.Endometrial receptivity is an important determinant of reproductive success,but it is unclear whether the effect of sow backfat thickness on litter size is associated with endometrial receptivity and whether melatonin treatment may have benefits.The present study seeks to answer these questions through in vitro and in vivo investigations.Results Excessive lipid deposition and lower melatonin levels in the uterus are detrimental to endometrial receptivity and embryo implantation in high backfat thickness sows.In cells treated with melatonin,the MT2/PI3K/LIF axis played a role in reducing lipid accumulation in porcine endometrial epithelium cells and improved endometrial receptivity.Furthermore,we found a reduction of lipids in the uterus after eight weeks of intraperitoneal administration of melatonin to HFD mice.Notably,melatonin treatment caused a significant reduction in the deposition of endometrial collagen,an increase in the number of glands,and repair of the pinopode structure,ultimately improving endometrial receptivity,promoting embryo implantation,and increasing the number of litter size of mice.Conclusions Collectively,the finding reveals the harmful effects of high backfat thickness sows on embryo implantation and highlight the role of melatonin and the MT2/PI3K/LIF axis in improving endometrial receptivity by enhancing metabolism and reducing the levels of uterine lipids in obese animals.
文摘Objective:To construct a pH-responsive paclitaxel(PTX)-exosome composite nanocarrier and investigate its inhibitory effect on the proliferation of endometrial cancer cells(HEC-1A).Methods:PTX was loaded into exosomes derived from adipose mesenchymal stem cells using the thin-film hydration method,and modified with polyethylene glycol-polylactic-co-glycolic acid(PEG-PLGA)to form nanocarriers(PTX-Exo-NPs).The particle size and morphology were detected by nanoparticle size and Zeta potential analyzer;drug encapsulation efficiency and drug loading capacity were determined by high-performance liquid chromatography;drug release behavior was evaluated in vitro under simulated acidic(pH 5.5)and physiological(pH 7.4)conditions;MTT assay and flow cytometry were used to detect the effects of the carrier on the proliferation,apoptosis,and cell cycle distribution of HEC-1A cells.Results:PTX-Exo-NPs exhibited a uniform spherical shape with a particle size of(128.5±5.2)nm,PTX encapsulation efficiency of 92.3%±2.1%,and drug loading capacity of 15.6%±0.8%.Drug release rate in the acidic environment(85.3%±2.1%within 72 h)was significantly higher than that in the physiological environment(48.0%±1.7%).In vitro experiments demonstrated that the proliferation inhibition rate of PTX-Exo-NPs on HEC-1A cells was higher than that of free PTX,with a lower IC50(0.64μM vs 4.70μM),and could induce cell apoptosis(apoptosis rate:28.7%±2.1%vs 14.2%±1.5%)and promote cell cycle arrest(G_2/M rate:45.3%±3.2%).Conclusion:PTX-Exo-NPs exhibit pH-responsive characteristics,which can target drug release through the acidic microenvironment,enhance the proliferation inhibition and pro-apoptotic effect on endometrial cancer cells,thus serving as a potential strategy for targeted therapy of endometrial tumors.
基金Supported by Natural Science Foundation of Shanghai,China,No.22ZR1458200Medical PhD Innovative Talent Base Project of Changning District,Shanghai,China,No.RCJD2021B09Key Specialty of Changning District,Shanghai,China,No.20231004.
文摘BACKGROUND Endometrial peristalsis(EmP)has been considered as a new indicator for eva-luating endometrial receptivity and is associated with embryo implantation rate and successful pregnancy rate.However,EmP remains understudied,incon-sistently measured,and poorly understood.New methods are needed urgently for better clinical practice.AIM To explore the value of EmP analysis(EmPA)technique in detecting and analy-zing EmP features automatically and quantitatively.METHODS One hundred and forty-five patients without abnormal findings on conventional transvaginal ultrasound were included in this study.A mid sagittal plane of ute-rus was recorded for 2 minutes in each patient and EmP features were analyzed using EmPA technique.EmP features in 50 patients were also analyzed by naked eyes analysis and the results of two methods were compared.RESULTS EmPA was unsuccessful in 9 patients(9/145,6.21%)due to the interference of respiratory or intestinal movement and was successful in 136 patients(136/145,93.79%),of whom 21 patients showed no EmP and 115 patients underwent EmPA and obtained quantitative results.The results of EmPA technique and naked eyes analysis about EmP intensity and transfer time had no significant consistence.Menstrual cycle,uterine position and history of induced abortion affected the quantitative results of EmPA.CONCLUSION EmPA technique provides noninvasive,quantitative and accurate detection and analysis of EmP in normal population and can evaluate EmP changes associated with menstrual cycle,uterine position and history of induced abortion.
文摘Objective To evaluate the impact of endometrial polyps(EP)on postoperative pregnancy outcomes in infertile women with endometriosis(EMs).Methods PubMed,Embase,The Cochrane Library,CNKI,VIP,SinoMed,and WanFang Data databases were searched to include clinical studies on the effect of EP on pregnancy outcomes in patients with EMs,published before August 31,2020.A meta-analysis was performed using Rev Man 5.3 software after two investigators independently screened the literature,extracted information,and evaluated the risk of bias of the included studies.Results The meta-analysis included ten studies(651 and 1,040 in the combined EP and uncomplicated EP groups,respectively).The spontaneous pregnancy rate,clinical pregnancy rate,and live birth rate were significantly lower in the group with combined EPs than in the group without combined EPs[Odd’s ratio(OR)=0.63,95%confidence interval(CI):0.50–0.80,P=0.0001;OR=0.63,95%CI:0.48–0.84,P=0.001;OR=0.63,95%CI:0.42–0.96,P=0.03],and the rate of embryonic abortion was significantly higher than that in the uncomplicated EP group[OR=3.10,95%CI:1.52–6.32,P=0.002].Conclusion EP may adversely affect pregnancy outcomes in patients with infertility and EMs.Even after surgical treatment,EP can still reduce natural pregnancy,clinical pregnancy,and live birth rates in infertile women with EMs and increase the risk of embryo arrest in these women.
文摘BACKGROUND Endometrial cancer(EC)is the most common gynecological malignancy in high-income countries,with incidence rates rising globally.Early and accurate diag-nosis is essential for improving outcomes.Transvaginal ultrasound(TVUS)remains a cost-effective first-line tool,and emerging techniques such as three-dimensional(3D)ultrasound(US),contrast-enhanced US(CEUS),elastography,and artificial intelligence(AI)-enhanced imaging may further improve diagnostic performance.AIM To systematically review recent advances in US-based imaging techniques for the diagnosis and staging of EC,and to compare their performance with magnetic resonance imaging(MRI).METHODS A systematic search of PubMed,Scopus,Web of Science,and Google Scholar was performed to identify studies published between January 2010 and March 2025.Eligible studies evaluated TVUS,3D-US,CEUS,elastography,or AI-enhanced US in EC diagnosis and staging.Methodological quality was assessed using the QUADAS-2 tool.Sensitivity,specificity,and area under the curve(AUC)were extracted where available,with narrative synthesis due to heterogeneity.RESULTS Forty-one studies met the inclusion criteria.TVUS demonstrated high sensitivity(76%–96%)but moderate specificity(61%–86%),while MRI achieved higher spe-cificity(84%–95%)and superior staging accuracy.3D-US yielded accuracy com-parable to MRI in selected early-stage cases.CEUS and elastography enhanced tissue characterization,and AI-enhanced US achieved pooled AUCs up to 0.91 for risk prediction and lesion segmentation.Variability in per-formance was noted across modalities due to patient demographics,equipment differences,and operator experi-ence.CONCLUSION TVUS remains a highly sensitive initial screening tool,with MRI preferred for definitive staging.3D-US,CEUS,elastography,and AI-enhanced techniques show promise as complementary or alternative approaches,particularly in low-resource settings.Standardization,multicenter validation,and integration of multi-modal imaging are needed to optimize diagnostic pathways for EC.
文摘BACKGROUND Claudin-6(CLDN6),a tight junction protein typically restricted to embryonic tissues,is re-expressed in various cancers.However,its prognostic significance in high-grade endometrial carcinoma(HGEC)remains unclear.AIM To investigate the expression pattern of CLDN6 in HGEC and assess its correlation with clinicopathological parameters and patient survival.METHODS Immunohistochemical analysis of CLDN6 expression was performed on formalinfixed,paraffin-embedded tissues from 80 patients diagnosed with HGEC.Associations between CLDN6 expression and histological subtype,the International Federation of Gynecology and Obstetrics(FIGO)stage,depth of myometrial invasion,lymphovascular space invasion,recurrence,and survival outcomes were statistically analysed.Univariate and multivariate Cox regression models were used to identify independent prognostic factors.RESULTS High CLDN6 expression was detected in a subset of HGEC patients and was significantly associated with nonendometrioid histology(P=0.026),advanced FIGO stage(P=0.015),deep myometrial invasion(P=0.038),and recurrence(P=0.002).While Kaplan-Meier analysis did not reveal a statistically significant difference in disease-free survival or overall survival between the high CLDN6 expression group and the low CLDN6 expression group,multivariate Cox regression revealed that CLDN6 overexpression was an independent predictor of shorter disease-free survival[hazard ratio(HR)=68.98,P=0.022]and overall survival(HR=24.023,P=0.038).CONCLUSION CLDN6 overexpression is associated with aggressive tumor features and poor clinical outcomes in HGEC,suggesting its utility as a prognostic biomarker and potential therapeutic target.
基金Supported by Wuxi Municipal Health Commission Maternal and Child Health Research Project,No.FYKY202301。
文摘BACKGROUND Seek highly effective treatment measures for improving mood and sleep.AIM To explore the effects of mood and depression in patients with endometrial cancer after cognitive behavioral therapy(CBT)and mindfulness-based stress reduction.METHODS In a prospective study,90 patients with diabetes,endometrial cancer,and depression were selected from January 2023 to January 2024 in our hospital.There were 45 patients in the control group and 45 patients in the observation group.In addition to the conventional treatment,the control group received cognitive behavioral treatment,and the observation group:Control group was given to compare changes in mood state and sleep quality before and after the intervention.Follow-up was performed3 months after treatment completion.RESULTS Before treatment,the mood and sleep quality scores between the two groups(P>0.05);in the observation group,the 5 negative mood scores were lower and lower than the control group;the 2 positive mood scores were higher than in the control group,and the difference was statistically significant(P<0.05);compared with before treatment,the 7 sleep quality scores and Pittsburgh sleep quality index scale total score in the observation group and lower in the control group(P<0.05).CONCLUSION In patients with diabetes and endometrial cancer,mood state and sleep quality significantly improved after CBT and breathing relaxation.These findings provide new and effective treatment strategies in clinical practice.
文摘Endometrial injury caused by repeated uterine procedures,infections,inflammation,or uterine artery dysfunction can deplete endometrial stem/progenitor cells and impair regeneration,thereby diminishing endometrial receptivity and evidently lowering the live birth,clinical pregnancy,and embryo implantation rates.Currently,safe and effective clinical treatment methods or gene-targeted therapies are unavailable,especially for severe endometrial injury.Umbilical cord mesenchymal stem cells and their extracellular vesicles are characterized by their simple collection,rapid proliferation,low immunogenicity,and tumorigenicity,along with their involvement in regulating angiogenesis,immune response,cell apoptosis and proliferation,inflammatory response,and fibrosis,Therefore,these cells and vesicles hold broad potential for application in endometrial repair.This article reviewed recent research on human umbilical cord mesenchymal stem cells as well as their extracellular vesicles in repairing endometrial injury.
基金the financial support from the Zhejiang Provincial Natural Science Foundation of China(No.LBY24H040012)Discipline Cluster of Oncology of Wenzhou Medical University(No.z1-2023007)+1 种基金the financial support from the National Natural Science Foundation of China(No.32401107)the financial support from the Discipline Cluster of Oncology of Wenzhou Medical University(No.z3-2023027)。
文摘Endometrial injury caused by intrauterine procedures can result in infertility and recurrent miscarriages,and the current clinical treatments are inadequate for effective endometrial repair.The implantation of anti-adhesion hydrogels combined with growth factors is a promising strategy to address endometrial injury.Insulin-like growth factor 1 is closely associated with endometrial growth and plays a crucial role in endometrial receptivity that is essential for fertility.However,its high cost,environmental sensitivity,and short biological half-life limit its practical applications.In this study,we developed a two-component peptide-based hydrogel consisting of a biotinylated peptide and an insulin-like growth factor 1(IGF-1)mimetic peptide,both of which were designed with self-assembly capabilities.The resultant hydrogel exhibited significant mechanical properties and retained its native IGF-1 bioactivity.In vivo experiments demonstrated that the hydrogel significantly facilitated proliferation and vascular restoration.Additionally,it effectively reduced fibrosis by decreasing collagen accumulation,restoring the expression of progesterone receptors,and enhancing endometrial receptivity,which are crucial for embryo implantation.These findings highlight the potential of the two-component peptide-based hydrogel as an innovative therapeutic approach for treating endometrial injury.
文摘BACKGROUND The microcystic,elongated,and fragmented(MELF)pattern of invasion in endometrioid endometrial carcinoma(EEC)is a special mode of myometrial invasion that has been recently recognized by the pathology community.Overex-pression of CXC chemokine receptor 4(CXCR4)in tumor cells contributes to tumor growth,invasion,angiogenesis,metastasis,and recurrence.AIM To explore the correlation between CXCR4 expression in EEC and MELF invasion and clinicopathological features.METHODS A total of 205 EEC patients treated at Peking University People’s Hospital from June 2020 to December 2021 were selected(60 cases with MELF invasion,145 cases without).The clinicopathological features of the two groups were compared,and expression of CXCR4 protein,estrogen receptor,and progesterone receptor was detected and compared by immunohistochemistry.RESULTS EEC with MELF invasion was significantly associated with low tumor grade,lymphovascular space invasion,deep myometrial invasion,cervical stromal involvement,and lymph node metastasis.There was a difference in CXCR4 expression between the two groups,with the MELF group having a significantly higher expression than the non-MELF group.CONCLUSION CXCR4 expression is significantly increased in EEC with MELF invasion and in the MELF invasion area,which may promote tumor invasion and metastasis and has some value for prognostic assessment.
基金Supported by the General Program of the Natural Science Foundation of Guangdong Province,No.2025A1515011163.
文摘This article comments on the study by Zhang et al,which proposed that exosomes derived from hypoxia-injured endometrial epithelial cells promote human umbilical cord mesenchymal stem cell migration and differentiation into endo-metrial epithelial cells via exosomal miR-137-3p.The authors demonstrated that miR-137-3p targets ubiquitin protein ligase E3C and activates signal transducer and activator of transcription 3 signaling,thereby driving epithelial lineage transition.While this study expands our understanding of exosome-mediated intercellular communication in endometrial repair,several key gaps remain.Notably,microRNA(miRNA)profiling was performed in human umbilical cord mesenchymal stem cells post-exosome treatment,not in the exosomes derived from hypoxia-injured endometrial epithelial cell themselves,leaving open whether miR-137-3p is directly transferred or indirectly induced.In addition,data on exosome characterization were unavailable,and the rationale for selecting miR-137-3p over other differentially expressed miRNAs was not well justified.Future studies should include direct exosomal miRNA content analysis,in vivo validation,and deeper mechanistic exploration of the ubiquitin protein ligase E3C-signal transducer and activator of transcription 3 ubiquitination axis to establish the clinical and biological relevance of this pathway.
文摘Endometrial thickness plays an important role in successful embryo implantation and normal pregnancy achievement.However,a thin endometrial layer(≤7 mm)may have a significant effect on microenvironment tolerance,which is further related to successful embryo implantation or conception,either naturally or after assisted reproductive technology.Moreover,this microenvironment tolerance shift induces hypoxic damage to endometrial epithelial cells(EECs),which results in altered signaling biomolecule secretion,including exosome content.In the context of endometrium regeneration,mesenchymal stromal cells(MSCs)and umbilical cord(UC)-derived stem cells have been applied in clinical trials with promising results.It has been recently shown that exosomes derived from hypoxic damaged EECs directly contribute to the increased migratory and regenerative abilities of UCs and MSCs.Specifically,microRNAs in exosomes secreted by the hypoxic damaged EECs,such as miR-214-5p and miR-21-5p,play a crucial role in the migratory capacity and differentiation ability of MSCs to EECs mediated through the signal transducer and activator of transcription 3(STAT3)signaling pathway.Taking into consideration the above information,UC-MSCs may be considered as a modern intervention for endometrial regeneration.
文摘This study by Zhang et al elucidates the role of exosome miR-137-3p targeting ubiquitin protein ligase E3C to activate signal transducer and activator of transcription 3 under hypoxia conditions,thereby promoting the migration and differentiation of human umbilical cord mesenchymal stem cells to endometrial epithelial cells.It emphasizes that exosomal miR-137-3p/ubiquitin protein ligase E3C/signal transducer and activator of transcription 3 axis is a promising pathway for endometrial regeneration.This article introduced the therapeutic potential of exosomal microRNAs in regenerative medicine while underscoring the need for standardized protocols in optimizing exosome delivery and validating molecular pathways for clinical translation.
基金the National Natural Science Foundation of China,No.82170406 and No.81970238the Royal Society United Kingdom,No.IEC\NSFC\201094.
文摘Exosomes derived from hypoxic endometrial epithelial cells are pivotal in cellular communication and tissue repair,offering new perspectives on reproductive health.This manuscript highlights the study by Zhang et al,which investigates the effects of miR-214-5p and miR-21-5p in hypoxic cell-derived exosomes on human umbilical cord mesenchymal stem cells.The study reveals that low levels of these microRNAs activate the signal transducer and activator of transcription 3 signaling pathway,enhancing human umbilical cord mesenchymal stem cell migration and differentiation.These findings provide novel insights into therapeutic strategies for improving endometrial health and addressing infertility linked to thin endometrium.
基金Supported by the National High Level Hospital Clinical Research Funding,No.2022-PUMCH-B-080 and No.2022-PUMCH-C-064.
文摘BACKGROUND Thin endometrium,leading cause of recurrent implantation failure and infertility,has been found to respond to exosomes.AIM To investigate the efficacy of exosomes in addressing the issue of thin endometrium.METHODS RNA sequencing and reverse transcription-quantitative polymerase chain reaction were employed to identify differentially expressed microRNAs(miRNAs)in human umbilical cord mesenchymal stem cell(hucMSC)treated with exosomes enriched with endometrial cell-derived components.Additionally,Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were conducted to highlight significant enrichment in specific biological pathways,molecular functions,and cellular components.Transwell and wound healing assays were performed to assess migratory potential,and western blotting was detected protein level.RESULTS A total of 53 differentially expressed miRNAs were identified in hucMSC treated with exosomes enriched with endometrial cell-derived components,comprising 27 upregulated and 26 downregulated miRNAs,which includes miR-137-3p.Enhanced migratory potential was observed in the Transwell and wound healing assays,and western blotting confirmed the epithelial differentiation of hucMSC and the increased p-signal transducer and activator of transcription 3.These effects were attributed to the upregulation of miR-137-3p.CONCLUSION miR-137-3p in exosomes from hypoxia-affected endometrial epithelial cell stimulates the signal transducer and activator of transcription 3 signaling pathway,enhancing the migration and differentiation of hucMSC into endometrial epithelial cell.
基金supported by the China Postdoctoral Science Foundation(2019M653776 and 2020M673516)the Natural Science Basis Research Plan in Shaanxi Province of China(2023-JC-QN-0181)+1 种基金the Shaanxi Livestock and Poultry Breeding Double-chain Fusion Key Project,China(2022GD-TSLD-46-0202)the Natural Science Fundation of Tibet Autonomous Region,China(XZ202101ZR0063G)。
文摘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.
基金supported by the Taishan Scholars Program of Shandong Province (No.tsqn201909101)the National Natural Science Foundation of China (Nos.21976114,92043202 and 91943301)。
文摘Tetrabromobisphenol A(TBBPA)and its derivatives widely exist in various environments and biota.Although the available data indicate that TBBPA exposure is highly associated with the increased incidence of endometrial cancer(EC),the effects of TBBPA and its main derivatives on EC proliferation and the involved crucial mechanism remain unclear.The present study aimed to investigate the effects of TBBPA and its derivatives under environmental concentrations on the proliferation of EC,and the crucial mechanism on the progression of EC caused by bromine fame retardants exposure.In this research,TBBPA and two of the most common TBBPA derivatives including TBBPA bis(2-hydroxyethyl ether)(TBBPABHEE)and TBBPA bis(dibromopropyl ether)(TBBPA-BDBPE)were screened for their capacities in induced EC proliferation and explored the related mechanism by in vitro cell culture model and in vivo mice model.Under environmental concentrations,TBBPA promoted the proliferation of EC,the main derivatives of TBBPA(TBBPA-BHEE and TBBPA-BDBPE)did not present the similar facilitation effects.The ubiquitination degradation of p53 was crucial in TBBPA induced EC proliferation,which resulted in the increase of downstream cell cycle and decrease of apoptosis.The further molecular docking result suggested the high affinity between TBBPA and ubiquitinated proteasome.This finding revealed the effects of TBBPA and its derivatives on EC proliferation,thus providing novel insights into the underlying mechanisms of TBBPA-caused EC.
