RESUMEN
OBJECTIVE: Endometrial polyp (EP) is a type of pathology that is quite common in clinical practice. Although its exact etiology is not fully known, there is evidence to support that it is sensitive to hormonal stimuli. We aimed to investigate the relationship between kisspeptin (KP) and EP by comparing the genetic (tissue-blood) and immunohistochemical (IHC) expression of KP in EP lesions in patients with normal endometrial findings. MATERIALS AND METHODS: A prospective case-control study of 50 patients with EP (N = 25) and normal endometrial findings (N = 25) on biopsy and/or excision material was performed. Blood and biopsy samples obtained from all patients were stored at -80 °C. KP gene expression levels were determined from paraffin blocks, and peripheral venous blood samples obtained from biopsy specimens and IHC-H-score analysis were performed from paraffin blocks. EP and matched controls were compared for KP. RESULTS: After IHC, the KP H-score of the control group was higher than the EP group, and this difference was statistically significant; H-score: control: 5 (++; 1-15); polyp: 1 (+; 0-12) (P < 0.05). Although KP expression in both tissue and blood was higher in the control group than in the EP group, this difference was not statistically significant (P > 0.05). No significant correlation was found between IHC H-score and KP expression levels in tissue and blood. According to the ROC analysis, the tissue and blood KP expression cut-off value and area under the curve (AUC) predicting the likelihood of developing EP were not significant (tissue KP: 1.04, AUC: 0.570, P = 0.388, sensitivity 56%, specificity 60%, Blood KP: 1.06, AUC: 0.569, P = 0.401, sensitivity 80%, specificity 40%). CONCLUSIONS: Decreased KP expression level in EP lesions may predict the diagnosis of EP, and in the future, KP may have therapeutic potential for benign gynecological pathologies such as polyps.
Asunto(s)
Inmunohistoquímica , Kisspeptinas , Pólipos , Humanos , Femenino , Pólipos/genética , Pólipos/metabolismo , Pólipos/patología , Kisspeptinas/genética , Kisspeptinas/metabolismo , Estudios de Casos y Controles , Enfermedades Uterinas/genética , Enfermedades Uterinas/metabolismo , Enfermedades Uterinas/patología , Enfermedades Uterinas/sangre , Estudios Prospectivos , Adulto , Endometrio/metabolismo , Endometrio/patología , Persona de Mediana EdadRESUMEN
Zearalenone (ZEA) is a mycotoxin produced by Fusarium fungi that has been shown to have adverse effects on human and animal health, particularly on the fertility of females. As a saponin derived from the medicinal plant Centella asiatica, asiaticoside (AS) has multiple bioactivities. This study aimed to investigate the protective effects of AS on ZEA-induced uterine injury and the underlying mechanism. In the present study, we demonstrated that AS could rescue ZEA-induced uterine histopathological damage and modulate the secretion of sex hormones, including progesterone (P4), luteinizing hormone (LH), and estradiol (E2), in ZEA-treated mice. Moreover, AS alleviated ZEA-induced damage to endometrial barrier function by upregulating the expression of tight junction proteins (ZO-1, occludin, and claudin-3). Further mechanistic investigations indicated that ZEA reduces the antioxidant capacity of uterine tissues, whereas AS improves the antioxidant capacity through activating the Nrf2 signaling pathway. Most notably, the protective effect of AS was blocked in Nrf2 gene knockout (Nrf2-/-) mice. Moreover, the p38/ERK MAPK pathway has been implicated in regulating ZEA toxicity and the beneficial effect of AS. Additionally, an Nrf2 inhibitor (ML385) weaken the suppressive effect of AS on the oxidative stress and MAPK pathway. AS also inhibits ZEA-induced apoptosis in uterine tissues via the PI3K/Akt signaling pathway. However, when the PI3K small molecule inhibitor LY294002 was co-administered, the ability of AS to suppress the expression of apoptosis-related proteins and inhibit ZEA-induced apoptosis decreased. Collectively, these findings reveal the involvement of multiple pathways and targets in the protective effect of AS against ZEA-induced uterine injury, providing a new perspective for the application of AS and the development of a ZEA antidote.
Asunto(s)
Apoptosis , Endometrio , Estrés Oxidativo , Triterpenos , Útero , Zearalenona , Animales , Femenino , Estrés Oxidativo/efectos de los fármacos , Triterpenos/farmacología , Zearalenona/toxicidad , Apoptosis/efectos de los fármacos , Ratones , Endometrio/efectos de los fármacos , Endometrio/metabolismo , Endometrio/patología , Útero/efectos de los fármacos , Útero/metabolismo , Útero/patología , Transducción de Señal/efectos de los fármacos , Enfermedades Uterinas/patología , Enfermedades Uterinas/metabolismo , Enfermedades Uterinas/inducido químicamente , Enfermedades Uterinas/prevención & control , Enfermedades Uterinas/genéticaRESUMEN
Pericytes are versatile cells integral to the blood vessel walls of the microcirculation, where they exhibit specific stem cell traits. They are essential in modulating blood flow, ensuring vascular permeability, and maintaining homeostasis and are involved in the tissue repair process. The human endometrium is a unique and complex tissue that serves as a natural scar-free healing model with its cyclical repair and regeneration process every month. The regulation of pericytes has gained increasing attention due to their involvement in various physiological and pathological processes. However, endometrial pericytes are less well studied compared to the pericytes in other organs. This review aims to provide a comprehensive overview of endometrial pericytes, with a focus on elucidating their physiological function and potential implications in uterine disorders.
Asunto(s)
Endometrio , Pericitos , Enfermedades Uterinas , Humanos , Pericitos/metabolismo , Endometrio/metabolismo , Endometrio/fisiología , Femenino , Enfermedades Uterinas/patología , Enfermedades Uterinas/fisiopatologíaRESUMEN
IL-33 belongs to the inflammatory factor family and is closely associated with the inflammatory response. However, its role in the development of intrauterine adhesions (IUAs) remains unclear. In this study, the role of IL-33 in the formation of IUAs after endometrial injury was identified via RNA sequencing after mouse endometrial organoids were transplanted into an IUA mouse model. Major pathological changes in the mouse uterus, consistent with the expression of fibrotic markers, such as TGF-ß, were observed in response to treatment with IL-33. This finding may be attributed to activation of the phosphorylation of downstream MAPK signaling pathway components, which are activated by the release of IL-33 in macrophages. Our study provides a novel mechanism for elucidating IUA formation, suggesting a new therapeutic strategy for the prevention and clinical treatment of IUAs.
Asunto(s)
Interleucina-33 , Sistema de Señalización de MAP Quinasas , Animales , Interleucina-33/metabolismo , Interleucina-33/genética , Femenino , Ratones , Adherencias Tisulares/metabolismo , Adherencias Tisulares/patología , Enfermedades Uterinas/patología , Enfermedades Uterinas/metabolismo , Enfermedades Uterinas/genética , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Transducción de Señal , Útero/metabolismo , Útero/patología , Endometrio/metabolismo , Endometrio/patología , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Proteínas Quinasas Activadas por Mitógenos/genéticaRESUMEN
Intrauterine adhesion (IUA) is manifestations of endometrial fibrosis and excessive extracellular matrix deposition. C1q/tumor necrosis factor-related protein-6 (CTRP6) is a newly identified adiponectin paralog which has been reported to modulate the fibrosis process of several diseases; however, the endometrial fibrosis function of CTRP6 remains unknown. Our study aimed to assess the role of CTRP6 in endometrial fibrosis and further explore the underlying mechanism. Here, we found that the expression of CTRP6 was downregulated in the endometrial tissues of IUA. In vitro experiments demonstrated the reduced level of CTRP6 in facilitated transforming growth factor-ß1 (TGF-ß1)-induced human endometrial stromal cells (HESCs). In addition, CTRP6 inhibited the expression of α-smooth muscle actin (α-SMA) and collagen I in TGF-ß1-treated HESCs. Mechanistically, CTRP6 activated the AMP-activated protein kinase (AMPK) and protein kinase B (AKT) pathway in HESCs, and AMPK inhibitor (AraA) or PI3K inhibitor (LY294002) pretreatment abolished the protective effect of CTRP6 on TGF-ß1-induced fibrosis. CTRP6 markedly decreased TGF-ß1-induced Smad3 phosphorylation and nuclear translocation, and AMPK or AKT inhibition reversed these effects. Notably, CTRP6-overexpressing treatment alleviated the fibrosis of endometrium in vivo. Therefore, CTRP6 ameliorates endometrial fibrosis, among which AMPK and AKT are essential for the anti-fibrotic effect of CTRP6 via the Smad3 pathway. Taken together, CTRP6 may be a potential therapeutic target for the treatment of intrauterine adhesion.
Asunto(s)
Endometrio , Fibrosis , Transducción de Señal , Proteína smad3 , Animales , Femenino , Humanos , Ratones , Adipoquinas/metabolismo , Colágeno , Endometrio/metabolismo , Endometrio/efectos de los fármacos , Endometrio/patología , Transducción de Señal/efectos de los fármacos , Proteína smad3/metabolismo , Proteína smad3/genética , Adherencias Tisulares/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Factores de Necrosis Tumoral/metabolismo , Factores de Necrosis Tumoral/genética , Enfermedades Uterinas/metabolismo , Enfermedades Uterinas/patologíaRESUMEN
The integration of barrier materials with pharmacological therapy is a promising strategy to treat intrauterine adhesions (IUAs). However, most of these materials are surgically implanted in a fixed shape and incongruence with the natural mechanical properties of the uterus, causing poor adaptability and significant discomfort to the patients. Herein, an injectable, biodegradable, and mechanically adaptive hydrogel loaded with platelet-rich plasma (PRP) is created by Lserine and allyl functionalized chitosan (ACS) to achieve efficient, comfortable, and minimally invasive treatment of IUAs. Lserine induces fast gelation and mechanical reinforcement of the hydrogel, while ACS introduces, imparting a good injectability and complaint yet strong feature to the hydrogel. This design enables the hydrogel to adapt to the complex geometry and match the mechanical properties of the uterine. Moreover, the hydrogel exhibits proper degradability, sustained growth factors (GFs) of PRP release ability, and good biocompatibility. Consequently, the hydrogel shows promising therapeutic efficacy by reducing collagen fiber deposition and facilitating endometrium cell proliferation, thereby restoring the fertility function of the uterus in an IUAs model of rats. Accordingly, the combination of Lserine and ACS-induced hydrogel with such advantages holds great potential for treating IUAs. STATEMENT OF SIGNIFICANCE: This research introduces a breakthrough in the treatment of intrauterine adhesions (IUAs) with an injectable, biodegradable and mechanically adaptive hydrogel using Lserine and allyl functionalized chitosan (ACS). Unlike traditional surgical treatments, this hydrogel uniquely conforms to the uterus's geometry and mechanical properties, offering a minimally invasive, comfortable, and more effective solution. The hydrogel is designed to release growth factors from platelet-rich plasma (PRP) sustainably, promoting tissue regeneration by enhancing collagen fiber deposition and endometrium cell proliferation. Demonstrated efficacy in a rat model of IUAs indicates its great potential to significantly improve fertility restoration treatments. This advancement represents a significant leap in reproductive medicine, promising to transform IUAs treatment with its innovative approach to achieving efficient, comfortable, and minimally invasive therapy.
Asunto(s)
Quitosano , Hidrogeles , Plasma Rico en Plaquetas , Ratas Sprague-Dawley , Serina , Femenino , Animales , Quitosano/química , Quitosano/farmacología , Adherencias Tisulares/patología , Hidrogeles/química , Hidrogeles/farmacología , Serina/química , Serina/farmacología , Ratas , Inyecciones , Útero/efectos de los fármacos , Útero/patología , Enfermedades Uterinas/patología , Enfermedades Uterinas/terapiaRESUMEN
BACKGROUND: Sarcoidosis is a systemic disease that can affect multiple organs. While pulmonary sarcoidosis is most commonly observed, renal sarcoidosis occurs less frequently. We herein report a case of sarcoidosis with an exceptionally rare distribution including renal lesions. CASE PRESENTATION: A 51-year-old Japanese female was referred because of bilateral parotid swelling and renal dysfunction. Computed tomography scan showed the swelling of bilateral kidneys, parotid glands, and uterus. Ga scintigraphy also showed remarkable accumulation in these organs. Renal biopsy and cytological evaluations of parotid gland and uterus were performed and she was diagnosed as sarcoidosis of these organs. Treatment was initiated with prednisolone 40 mg/day and then renal dysfunction subsequently improved. In addition, the swelling of parotid glands and uterus improved and Ga accumulation in each organ had disappeared. CONCLUSION: This is a first case of renal sarcoidosis complicated by parotid glands and uterus lesions. Pathological findings and the reactivity observed in Ga scintigraphy indicated the presence of lesions in these organs.
Asunto(s)
Enfermedades Renales , Sarcoidosis , Humanos , Femenino , Persona de Mediana Edad , Sarcoidosis/complicaciones , Sarcoidosis/diagnóstico por imagen , Sarcoidosis/tratamiento farmacológico , Enfermedades Renales/diagnóstico por imagen , Enfermedades Renales/patología , Enfermedades Renales/complicaciones , Enfermedades Renales/etiología , Glándula Parótida/patología , Glándula Parótida/diagnóstico por imagen , Enfermedades Uterinas/complicaciones , Enfermedades Uterinas/patología , Enfermedades Uterinas/diagnóstico por imagen , Prednisolona/uso terapéutico , Enfermedades de las Parótidas/diagnóstico por imagen , Enfermedades de las Parótidas/etiología , Enfermedades de las Parótidas/patología , Cintigrafía , Tomografía Computarizada por Rayos XRESUMEN
Uterine pathologies pose a challenge to women's health on a global scale. Despite extensive research, the causes and origin of some of these common disorders are not well defined yet. This study presents a comprehensive analysis of transcriptome data from diverse datasets encompassing relevant uterine pathologies such as endometriosis, endometrial cancer and uterine leiomyomas. Leveraging the Comparative Analysis of Shapley values (CASh) technique, we demonstrate its efficacy in improving the outcomes of the classical differential expression analysis on transcriptomic data derived from microarray experiments. CASh integrates the microarray game algorithm with Bootstrap resampling, offering a robust statistical framework to mitigate the impact of potential outliers in the expression data. Our findings unveil novel insights into the molecular signatures underlying these gynecological disorders, highlighting CASh as a valuable tool for enhancing the precision of transcriptomics analyses in complex biological contexts. This research contributes to a deeper understanding of gene expression patterns and potential biomarkers associated with these pathologies, offering implications for future diagnostic and therapeutic strategies.
Asunto(s)
Endometriosis , Perfilación de la Expresión Génica , Leiomioma , Transcriptoma , Femenino , Humanos , Transcriptoma/genética , Endometriosis/genética , Endometriosis/patología , Leiomioma/genética , Leiomioma/patología , Perfilación de la Expresión Génica/métodos , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Neoplasias Uterinas/genética , Neoplasias Uterinas/patología , Enfermedades Uterinas/genética , Enfermedades Uterinas/patología , AlgoritmosRESUMEN
BACKGROUND: Insulin resistance (IR) induces hyperinsulinemia, which activates downstream signaling pathways such as the phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) pathway, ultimately leading to abnormal proliferation and apoptosis of endometrial cells. This is thought to be a key pathogenic mechanism underlying the development of endometrial polyps (EP). This study aims to investigate the relationship between IR and the development of EP, the expression levels of downstream signaling molecules, including PI3K and AKT, and related laboratory parameters were examined. METHODS: A total of 100 patients who visited the gynecology outpatient clinic of Zhongda Hospital affiliated with Southeast University from May 2021 to March 2023 and were diagnosed with abnormal endometrial echoes by vaginal ultrasound and underwent hysteroscopic diagnostic curettage were enrolled in this study. General data and relevant hematological indicators were compared, and intraoperative specimens were obtained for pathological examination. Possible factors influencing the development of endometrial polyps were analyzed using Pearson correlation analysis and logistic regression analysis. RESULTS: In terms of body mass index, waist circumference, fasting insulin, insulin resistance index, serum total testosterone, and free testosterone index, women of childbearing age in the endometrial polyp group had higher values than those in the non-polyp group, while sex hormone-binding globulin in the endometrial polyp group was lower than that in the non-polyp group, and the differences were statistically significant (P < 0.05). The expression scores and mRNA expression levels of PI3K and AKT proteins were higher in the EP group than in the non-EP group (p < 0.05). Pearson correlation analysis showed a positive correlation between HOMA-IR and the expression scores of PI3K and AKT proteins (p < 0.01). CONCLUSIONS: Insulin resistance and abnormal activation of the phosphatidylinositol 3-kinase/protein kinase B signaling pathway may be potential pathogenic mechanisms for the development of endometrial polyps.
Asunto(s)
Resistencia a la Insulina , Fosfatidilinositol 3-Quinasas , Pólipos , Proteínas Proto-Oncogénicas c-akt , Humanos , Femenino , Proteínas Proto-Oncogénicas c-akt/metabolismo , Adulto , Fosfatidilinositol 3-Quinasas/metabolismo , Persona de Mediana Edad , Enfermedades Uterinas/metabolismo , Enfermedades Uterinas/patología , Índice de Masa Corporal , Transducción de Señal , Endometrio/metabolismo , Endometrio/patología , Globulina de Unión a Hormona Sexual/metabolismo , Globulina de Unión a Hormona Sexual/análisis , Testosterona/sangre , Insulina/metabolismo , Insulina/sangreRESUMEN
This case report discusses a diagnosis of uterine torsion in an 84-year-old woman who presented with five days of right lower quadrant abdominal pain, nausea, vomiting, constipation, and poor intake. Computed tomography (CT) imaging demonstrated a whorled configuration at the junction of the cervix and lower uterine segment, with the left gonadal vein crossing midline, and two previously known right leiomyomas now appearing on the left. These findings were consistent with the diagnosis of uterine torsion. She then underwent an urgent exploratory laparotomy, and the uterus was found to be dextroverted 270 degrees, with dark mottled purple tissue and engorged vessels. A supracervical hysterectomy and bilateral salpingo-oopherectomy were performed. Final pathology demonstrated extensive necrosis. This case reviews the classic presentation and imaging findings for the rare diagnosis of uterine torsion and options for management of both non-gravid and gravid patients.
Asunto(s)
Leiomioma , Posmenopausia , Tomografía Computarizada por Rayos X , Anomalía Torsional , Neoplasias Uterinas , Humanos , Femenino , Leiomioma/cirugía , Leiomioma/diagnóstico por imagen , Leiomioma/complicaciones , Leiomioma/patología , Anciano de 80 o más Años , Anomalía Torsional/diagnóstico por imagen , Anomalía Torsional/cirugía , Neoplasias Uterinas/diagnóstico por imagen , Neoplasias Uterinas/cirugía , Neoplasias Uterinas/complicaciones , Neoplasias Uterinas/patología , Enfermedades Uterinas/diagnóstico por imagen , Enfermedades Uterinas/cirugía , Enfermedades Uterinas/patología , Histerectomía , Diagnóstico DiferencialRESUMEN
STUDY OBJECTIVE: To evaluate the efficacy and pregnancy outcomes of intrauterine balloon and intrauterine contraceptive devices in the prevention of adhesion reformation following hysteroscopic adhesiolysis in infertile women with moderate to severe intrauterine adhesion. DESIGN: A prospective, randomized, controlled trial study. SETTING: A tertiary university hospital. PATIENTS: A total of 130 patients with moderate (American Fertility Society [AFS] score of 5-8) and severe (AFS score of 9-12) intrauterine adhesions were recruited. INTERVENTIONS: 86 patients were evenly allocated to group treated with an IUD for 1 month and group treated with an IUD for 2 months. 44 patients were allocated to group treated with a Foley catheter balloon.(IUD: Yuangong IUD). MEASUREMENTS AND MAIN RESULTS: The primary outcome measures were the AFS score, endometrial thickness, and pregnancy outcome. After hysteroscopy, the AFS score was significantly decreased(P<0.05), whereas endometrial thickness was significantly increased across the three groups(P<0.001). Notably, the decline in the AFS score in the balloon group was greater than that in the IUD-1-month group and IUD-2-month group(P<0.01), with no significant difference between the IUD groups(P = 0.298). Lastly, In addition, the extent of the increase in endometrial thickness(P = 0.502) and the pregnancy outcomes(P = 0.803) in the three groups were not significantly different. CONCLUSION: Inserting a balloon or placing an IUD for one or two months can effectively lower the risk of adhesion recurrence and restore the shape of the uterine cavity. While the therapeutic effect of the balloon was superior to that of the IUD, no significant differences were observed in the one-month and two-month IUD groups. TRIAL REGISTRATION: This research was registered in the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/enIndex.aspx ); Clinical trial registry identification number: ChiCTR-IOR-17,011,943 ( http://www.chictr.org.cn/showprojen.aspx?proj=17979 ). Date of trial registration: July 11, 2017.
Asunto(s)
Histeroscopía , Infertilidad Femenina , Dispositivos Intrauterinos , Resultado del Embarazo , Humanos , Femenino , Adherencias Tisulares/prevención & control , Adulto , Embarazo , Histeroscopía/métodos , Infertilidad Femenina/terapia , Infertilidad Femenina/etiología , Infertilidad Femenina/prevención & control , Estudios Prospectivos , Enfermedades Uterinas/cirugía , Enfermedades Uterinas/complicaciones , Enfermedades Uterinas/prevención & control , Enfermedades Uterinas/patología , Resultado del Tratamiento , Índice de EmbarazoRESUMEN
The metritis complex (MC), a group of post-partum uterine diseases, is associated with increased treatment costs and reduced milk yield and fertility. The goal of this study was to identify genetic variants, genes, or genomic regions that modulate MC disease. A genome-wide association study was performed using a single-locus mixed linear model of 1967 genotypes (624,460 SNPs) and metritis complex records. Then, in-silico functional analyses were performed to detect biological mechanisms and pathways associated with the development of MC. The ATP8A2, COX16, AMN, and TRAF3 genes, located on chromosomes 12, 10, and 21, were associated with MC at p ≤ 0.0001. These genes are involved in the regulation of cholesterol metabolism in the stromal tissue of the uterus, which can be directly associated with the mode of transmission for pathogens causing the metritis complex. The modulation of cholesterol abundance alters the efficiency of virulence factors and may affect the susceptibility of the host to infection. The SIPA1L1, DEPDC5, and RNF122 genes were also significantly associated with MC at p ≤ 0.0001 and are involved in the PI3k-Akt pathway, responsible for activating the autophagic processes. Thus, the dysregulation of these genes allows for unhindered bacterial invasion, replication, and survival within the endometrium.
Asunto(s)
Enfermedades de los Bovinos , Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido Simple , Animales , Femenino , Bovinos , Enfermedades de los Bovinos/genética , Enfermedades de los Bovinos/microbiología , Predisposición Genética a la Enfermedad , Endometritis/genética , Endometritis/microbiología , Endometritis/veterinaria , Endometritis/patología , Enfermedades Uterinas/genética , Enfermedades Uterinas/microbiología , Enfermedades Uterinas/patologíaRESUMEN
OBJECTIVE: Chronic endometritis (CE) is an inflammatory condition with several different risk factors. We aimed to examine whether intrauterine abnormalities, such as endometrial polyps, submucosal myomas, intrauterine adhesions, or a septate uterus, were associated with an increased likelihood of developing chronic endometritis. METHODS: A cross-sectional study was conducted on 335 infertile women who underwent hysteroscopy surgery at the Ayatollah Taleghani Hospital Infertility Center, affiliated by Shahid Beheshti University of Medical Sciences, in 2022. All participants in the study underwent hysteroscopic surgery, which allowed for direct visualization of the intrauterine cavity, and endometrial biopsies were taken for further analysis. To characterize endometritis, plasma cell infiltration was assessed. Patients with ≥5 plasma cells observed in 10 high-power fields were defined as having chronic endometritis. RESULTS: Endometritis was observed in 51.3% of the patients, totaling 172 individuals. Logistic regression analysis revealed that patients with endometrial polyps had 5.2 times higher odds of developing endometritis compared to patients without polyps (95% CI = 2.9, 9.2) (p-value <0.001). Similarly, patients with intrauterine adhesions had a significant increase in the odds of endometritis (OR = 4.6, 95% CI = 2.1, 10.1) (p-value <0.001). CONCLUSIONS: Treatment or removal of endometrial abnormalities through hysteroscopic procedures may help to reduce the risk of chronic endometritis and improve fertility outcomes. Further research is necessary.
Asunto(s)
Endometritis , Histeroscopía , Infertilidad Femenina , Humanos , Femenino , Estudios Transversales , Endometritis/epidemiología , Adulto , Infertilidad Femenina/epidemiología , Prevalencia , Útero/patología , Útero/cirugía , Útero/anomalías , Enfermedades Uterinas/epidemiología , Enfermedades Uterinas/complicaciones , Enfermedades Uterinas/cirugía , Enfermedades Uterinas/patología , Enfermedad Crónica , Pólipos/epidemiología , Pólipos/cirugía , Pólipos/patología , Pólipos/complicaciones , Anomalías Urogenitales/epidemiología , Anomalías Urogenitales/complicaciones , Anomalías Urogenitales/cirugía , Adherencias Tisulares/epidemiología , Adherencias Tisulares/complicaciones , Factores de RiesgoRESUMEN
Transplantation of bone marrow mesenchymal stem cells (BMSCs) has demonstrated promising clinical utility in the treatment of endometrial injury and the restoration of fertility. However, since the efficacy of BMSCs after transplantation is not stable, it is very important to find effective ways to enhance the utilisation of BMSCs. Electroacupuncture (EA) has some positive effects on the chemotaxis of stem cells and diseases related to uterine injury. In this study, we established the intrauterine adhesion (IUA) model of the Sprague-Dawley rat using lipopolysaccharide infection and mechanical scratching. Phosphate-buffered saline, BMSCs alone, and BMSCs combined with EA were randomly administered to the rats. Fluorescent cell labelling showed the migration of transplanted BMSCs. H&E staining, Masson staining, Western blot, immunohistochemistry, ELISA, and qRT-PCR were utilised to detect changes in endometrial morphology and expressions of endometrial receptivity-related factors, endometrial pro-inflammatory factors, and fibrosis factors. Finally, we conducted a fertility test to measure the recovery of uterine function. The results showed that EA promoted transplanted BMSCs to migrate into the injured uterus by activating the SDF-1/CXCR4 axis. Endometrial morphology showed the most significant improvement in the BMSC + EA group. The expressions of endometrial pro-inflammatory factors and fibrosis indexes in the BMSC + EA group were lower than those in the model and BMSC groups. Further studies revealed that the expression of endometrial receptivity-related factors and the number of embryos implanted on day 8 of gestation increased in the BMSC + EA group compared with the model group and the BMSC group.
Asunto(s)
Electroacupuntura , Trasplante de Células Madre Mesenquimatosas , Ratas Sprague-Dawley , Enfermedades Uterinas , Animales , Femenino , Electroacupuntura/métodos , Trasplante de Células Madre Mesenquimatosas/métodos , Adherencias Tisulares , Ratas , Enfermedades Uterinas/terapia , Enfermedades Uterinas/patología , Endometrio/metabolismo , Terapia Combinada , Recuperación de la Función , Útero , Células Madre Mesenquimatosas , Receptores CXCR4/metabolismo , Quimiocina CXCL12/metabolismo , Modelos Animales de EnfermedadRESUMEN
Endometrial polyps (EPs) are benign overgrowths of the endometrial tissue lining the uterus, often causing abnormal bleeding or infertility. This study analyzed gene expression differences between EPs and adjacent endometrial tissue to elucidate intrinsic abnormalities promoting pathological overgrowth. RNA sequencing of 12 pairs of EPs and the surrounding endometrial tissue from infertile women revealed 322 differentially expressed genes. Protein-protein interaction network analysis revealed significant alterations in specific signaling pathways, notably Wnt signaling and vascular smooth muscle regulation, suggesting these pathways play critical roles in the pathophysiology of EPs. Wnt-related genes DKK1 and DKKL1 were upregulated, while GPC3, GREM1, RSPO3, SFRP5, and WNT10B were downregulated. Relevant genes for vascular smooth muscle contraction were nearly all downregulated in EPs, including ACTA2, ACTG2, KCNMB1, KCNMB2, MYL9, PPP1R12B, and TAGLN. Overall, the results indicate fundamental gene expression changes promote EP formation through unrestrained growth signaling and vascular defects. The intrinsic signaling abnormalities likely contribute to clinical symptoms of abnormal uterine bleeding and infertility common in EP patients. This analysis provides molecular insights into abnormal endometrial overgrowth to guide improved diagnostic and therapeutic approaches for this troublesome women's health condition. Confirmation of expanded cohorts and further investigations into implicated regulatory relationships are warranted.
Asunto(s)
Infertilidad Femenina , Pólipos , Enfermedades Uterinas , Humanos , Femenino , Infertilidad Femenina/patología , Enfermedades Uterinas/patología , Endometrio/patología , Pólipos/patología , Glipicanos , Péptidos y Proteínas de Señalización IntercelularRESUMEN
Intrauterine adhesions (IUA) are the most common cause of uterine infertility, and conventional treatments have not consistently achieved satisfactory pregnancy rates. Stem cell therapy shows promising potential for the clinical treatment of IUA. Although various advanced biomaterials have been designed for delivering stem cells to the uterine cavity, there remain significant challenges, particularly in devising therapeutic strategies for clinical application that minimize surgical incisions and conform to the intricate structure of uterine cavity. Herein, an injectable hydrogel loaded with human umbilical cord-derived mesenchymal stem cells (UCMSCs) was synthesized via the Diels-Alder click reaction for endometrial regeneration and fertility restoration, exhibiting suitable mechanical properties, good biocompatibility, and desirable degradation properties. Notably, this hydrogel permitted minimally invasive administration and integrated seamlessly with surrounding tissue. Our study revealed that the UCMSCs-laden injectable hydrogel enhanced cell proliferation, migration, angiogenesis, and exhibited anti-fibrotic effects in vitro. The implantation of this hydrogel significantly facilitated endometrium regeneration and restored fertility in a rat endometrial damage model. Mechanistically, in vivo results indicated that the UCMSCs-laden injectable hydrogel effectively promoted macrophage recruitment and facilitated M2 phenotype polarization. Collectively, this hydrogel demonstrated efficacy in regenerating damaged endometrium, leading to the restoration of fertility. Consequently, it holds promise as a potential therapeutic strategy for endometrial damage and fertility decline arising from intrauterine adhesions. STATEMENT OF SIGNIFICANCE: Severe endometrial traumas frequently lead to intrauterine adhesions and subsequent infertility. Stem cell therapy shows promising potential for the clinical treatment of IUA; however, challenges remain, including low delivery efficiency and compromised stem cell activity during the delivery process. In this study, we fabricated an injectable hydrogel loaded with UCMSCs via the Diels-Alder click reaction, which exhibited unique bioorthogonality. The in situ-gelling hydrogels could be introduced through a minimally invasive procedure and adapt to the intricate anatomy of the uterus. The UCMSCs-laden injectable hydrogel promoted endometrial regeneration and fertility restoration in a rat endometrial damage model, efficaciously augmenting macrophage recruitment and promoting their polarization to the M2 phenotype. The administration of UCMSCs-laden injectable hydrogel presents a promising therapeutic strategy for patients with severe intrauterine adhesion.
Asunto(s)
Infertilidad , Células Madre Mesenquimatosas , Enfermedades Uterinas , Embarazo , Femenino , Humanos , Ratas , Animales , Hidrogeles/química , Enfermedades Uterinas/terapia , Enfermedades Uterinas/metabolismo , Enfermedades Uterinas/patología , Endometrio/patología , Infertilidad/metabolismo , Infertilidad/patología , Adherencias Tisulares/terapia , Adherencias Tisulares/metabolismo , Cordón Umbilical/metabolismoRESUMEN
The endometrium undergoes cyclical changes in response to hormones and there is a certain degree of heterogeneity among individuals. In vivo identification of the physiologic changes of the endometrium and the pathologic process of related diseases is challenging. There have been recent advances in the use of organoids that mimic the characteristics of the corresponding organs and the morphologic, functional, and personalized characteristics involved in different stages of diseases. In this paper, we discuss the process of creating endometrial organoids, cell sources, types of extracellular matrices, and their application in the study of physiologic endometrial states and various diseases.
Asunto(s)
Endometrio , Organoides , Enfermedades Uterinas , Humanos , Femenino , Endometrio/patología , Enfermedades Uterinas/patología , Matriz ExtracelularRESUMEN
BACKGROUND: The monthly regeneration of human endometrial tissue is maintained by the presence of human endometrial mesenchymal stromal/stem cells (eMSC), a cell population co-expressing the perivascular markers CD140b and CD146. Endometrial regeneration is impaired in the presence of intrauterine adhesions, leading to infertility, recurrent pregnancy loss and placental abnormalities. Several types of somatic stem cells have been used to repair the damaged endometrium in animal models, reporting successful pregnancy. However, the ability of endometrial stem cells to repair the damaged endometrium remains unknown. METHODS: Electrocoagulation was applied to the left uterine horn of NOD/SCID mice causing endometrial injury. Human eMSC or PBS was then injected into the left injured horn while the right normal horn served as controls. Mice were sacrificed at different timepoints (Day 3, 7 and 14) and the endometrial morphological changes as well as the degree of endometrial injury and repair were observed by histological staining. Gene expression of various inflammatory markers was assessed using qPCR. The functionality of the repaired endometrium was evaluated by fertility test. RESULTS: Human eMSC successfully incorporated into the injured uterine horn, which displayed significant morphological restoration. Also, endometrium in the eMSC group showed better cell proliferation and glands formation than the PBS group. Although the number of blood vessels were similar between the two groups, gene expression of VEGF-α significantly increased in the eMSC group. Moreover, eMSC had a positive impact on the regeneration of both stromal and epithelial components of the mouse endometrium, indicated by significantly higher vimentin and CK19 protein expression. Reduced endometrial fibrosis and down-regulation of fibrosis markers were also observed in the eMSC group. The eMSC group had a significantly higher gene expression of anti-inflammatory factor Il-10 and lower mRNA level of pro-inflammatory factors Ifng and Il-2, indicating the role of eMSC in regulation of inflammatory reactions. The eMSC group showed higher implantation sites than the PBS group, suggesting better endometrial receptivity with the presence of newly emerged endometrial lining. CONCLUSIONS: Our findings suggest eMSC improves regeneration of injured endometrium in mice.
Asunto(s)
Células Madre Mesenquimatosas , Enfermedades Uterinas , Ratones , Femenino , Humanos , Embarazo , Animales , Ratones Endogámicos NOD , Ratones SCID , Placenta/patología , Endometrio/metabolismo , Endometrio/patología , Enfermedades Uterinas/terapia , Enfermedades Uterinas/metabolismo , Enfermedades Uterinas/patología , FibrosisRESUMEN
Intrauterine adhesions (IUA), the main cause of secondary infertility in women, result from irreversible fibrotic repair of the endometrium due to inflammation or human factors, accompanied by disruptions in the repair function of endometrial stem cells. This significantly impacts the physical and mental health of women in their childbearing years. Telocytes (TCs), a distinctive type of interstitial cells found in various tissues and organs, play diverse repair functions due to their unique spatial structure. In this study, we conduct the inaugural exploration of the changes in TCs in IUA disease and their potential impact on the function of stem cells. Our results show that in vivo, through double immunofluorescence staining (CD34+/Vimentin+; CD34+/CD31-), as endometrial fibrosis deepens, the number of TCs gradually decreases, telopodes shorten, and the three-dimensional structure becomes disrupted in the mouse IUA mode. In vitro, TCs can promote the proliferation and cycle of bone mesenchymal stem cells (BMSCs) by promoting the Wnt/ß-catenin signaling pathway, which were inhibited using XAV939. TCs can promote the migrated ability of BMSCs and contribute to the repair of stem cells during endometrial injury. In addition, TCs can inhibit the apoptosis of BMSCs through the Bcl-2/Bax pathway. In conclusion, our study demonstrates, for the first time, the resistance role of TCs in IUA disease, shedding light on their potential involvement in endometrial repair through the modulation of stem cell function.
Asunto(s)
Células Madre Mesenquimatosas , Telocitos , Enfermedades Uterinas , Humanos , Ratones , Femenino , Animales , Enfermedades Uterinas/metabolismo , Enfermedades Uterinas/patología , Endometrio/patología , Células Madre Mesenquimatosas/metabolismo , Telocitos/metabolismo , Vía de Señalización Wnt , Modelos Animales de EnfermedadRESUMEN
Mesenchymal stem cells play important roles in repairing injured endometrium. However, the molecular targets and potential mechanism of the endometrial recipient cells for stem cell therapy in intrauterine adhesion (IUA) are poorly understood. In this study, umbilical cord mesenchymal stem-cell-conditioned medium (UCMSCs-CM) produced positive effects on a Transforming growth factor beta (TGF-ß) induced IUA cell model. RNA-sequencing was performed on clinical IUA tissues, and the top 40 upregulated and top 20 downregulated mRNAs were selected and verified using high-throughput (HT) qPCR in both tissues and cell models. Based on a bioinformatic analysis of RNA-sequencing and HT-qPCR results, 11 mRNAs were uncovered to be the intervention targets of UCMSCs-CM on IUA endometrium cell models. Among them, IGFBP3 was striking as a key pathogenic gene and a potential diagnostic marker of IUA, which exhibited the area under the curve (AUC), sensitivity, specificity were 0.924, 93.1% and 80.6%, respectively in 60 endometrial tissues. The silencing of IGFBP3 exerted positive effects on the IUA cell model through partially upregulating MMP1 and KLF2. In conclusion, RNA-sequencing combined with HT qPCR based on clinical tissues and IUA cell models were used in IUA research and our results may provide some scientific ideas for the diagnosis and treatment of IUA.