RESUMEN

This study aimed to evaluate the localised effects of intrauterine ozone therapy on endometrial recovery in mares with endometritis. Our investigation assessed changes in gene expression profiles of anti-inflammatory (IL-1RA and IL-10), proinflammatory (IL-R1B3i and TNFα) and pleiotropic (IL-6) cytokines, along with detailed histological measurements of epithelial and endometrial thickness and the glandular area ratio. Twenty mares were assigned to a 2 × 2 factorial design based on endometritis diagnosis and treatment (control or 42 µg/mL ozone insufflation), resulting in four groups: NC (negative for endometritis/control), NO (negative/ozone), PC (positive/control) and PO (positive/ozone). Oestrus was induced with 2 mg of oestradiol benzoate on Days -1, 1 and 3, plus 1 mg on Day 5. Day 0 marked the initial uterine treatment, followed by insufflations on Days 1 and 2 with O3 (ozone) or O2 (control). Uterine biopsies were taken before treatment on Day 0 and Day 6 for histological analysis and gene expression assessment. Data were analysed using a statistical model that included endometritis status, treatment type, biopsy times (D0 and D6) and their interactions, analysed with Proc Glimmix. Regardless of treatment or endometritis status, significant biopsy effects (p < 0.01) indicated increased epithelial height and endometrial thickness in Day 6 samples. Analysis of IL-1 and TNFα revealed a significant interaction (p < 0.05) among endometritis, treatment and biopsy, with higher IL-1B3i expression on Day 6 in the PC group. The treatment effect (p < 0.04) showed a higher frequency (p < 0.01) of animals with positive modulation in the PC group (66.7%) versus the PO group (0.0%). An interaction effect (p = 0.08) between endometritis and treatment resulted from higher IL-1RA expression on Day 6 in the PC group compared to the PO group. Biopsy effect was significant for IL-10 (p < 0.01), indicating higher values in the second sample associated with tissue repair. In the short-term evaluation, ozone therapy did not influence endometrial morphology and may modulate cytokine expression, specifically the reduction in IL-1 and TNFα levels. Therefore, this therapy appears to be a safe and potentially effective treatment for modulating the inflammatory response in mares with endometritis.

Asunto(s)

Citocinas , Endometritis , Enfermedades de los Caballos , Ozono , Útero , Animales , Femenino , Ozono/farmacología , Endometritis/veterinaria , Endometritis/tratamiento farmacológico , Caballos , Enfermedades de los Caballos/tratamiento farmacológico , Útero/patología , Citocinas/genética , Citocinas/metabolismo , Endometrio/efectos de los fármacos , Endometrio/metabolismo , Endometrio/patología , Estradiol/farmacología , Estradiol/análogos & derivados , Transcriptoma

RESUMEN

OBJECTIVE: Aim: To clarify the association between different types of uterine contractility dysfunction and the inflammation of the uterus and chorioamniotic membranes. PATIENTS AND METHODS: Materials and Methods: The association between the inflammation of the uterine layers, chorioamniotic membranes, umbilical cord, and different types of labor activity abnormalities was examined in 382 patients with singleton pregnancies at 28-42 weeks' gestation who underwent Caesarean section (CS) for abnormal uterine contractions and other complications. Statistical analyses included the Mann-Whitney U, Chi-squared test, and logistic regression. RESULTS: Results: In the control group, slight infiltration with polymorphonuclear leukocytes (PMNs) and macrophages of the myometrium and decidua of the lower uterine segment at term pregnancy was found in 59.7% and 73.6% of cases. The main clinical risk factors for placental and decidual membrane inflammation in patients with excessive uterine activity (EUA) were prematurity, multiparity, group B streptococcus (GBS) colonization, and duration of ruptured fetal membranes before the CS. Moderate or marked myometrial inflammation of both uterine segments in the EUA group was diagnosed only in patients with cervical dilation of >6 cm and duration of labor of >8h. In women with hypotonic uterine activity (HUA), decidual and myometrial inflammation was significantly associated with nulliparity and intrapartum factors, such as protracted active first stage of labor, advanced cervical dilation, and number of vaginal examinations. In all cases, inflammation of the myometrium was accompanied by deciduitis. CONCLUSION: Conclusions: Mild inflammation of the decidual membrane and myometrium of the lower segment at term pregnancy is a common physiological phenomenon contributing to labor initiation. Uterine hyperfunction comes as the response of the unaffected myometrium to the release of high concentrations of proinflammatory cytokines produced by the inflamed decidual and chorioamniotic membranes into the bloodstream. Marked myometrial inflammation that occurs in prolonged labor is an additional factor aggravating the hypotonic uterine activity.

Asunto(s)

Útero , Humanos , Femenino , Embarazo , Adulto , Útero/patología , Contracción Uterina , Miometrio/patología , Cesárea/efectos adversos , Corioamnionitis/patología , Complicaciones del Trabajo de Parto , Inflamación/patología , Factores de Riesgo

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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/genética

RESUMEN

The position of the internal os of the cervix reported in the literature was inconsistent on MRI images. Additionally, the practical impactful data influencing the internal os located by MRI is limited. We aimed to confirm the position of the internal os of the cervix on MRI images, and the influencing factors locating the the internal os by MRI. A single-center retrospective study was conducted. Data from 175 patients who underwent total hysterectomy for stage I endometrial cancer were collected. The internal os of the cervix is positioned as the starting point for measuring the length of the cervix on MRI images. On dynamic contrast-enhanced MRI (DCE-MRI), the section formed by the enhancement difference between the uterus and cervix, and on T2-weighted imaging(T2WI), the section formed by the physiological curvature of the uterus and the low signal intensity of the cervical stroma were used as starting points. The results showed no statistically significant difference compared with the removed uterus specimens (p = 0.208, p = 0.571, p = 0.804). A history of cesarean section(p < 0.001), irregular vaginal bleeding for more than three months(p < 0.001), cervical adenomyosis(p = 0.043), and premenopause(p = 0.001) were not conducive to locating the internal os of the cervix by MRI. Our findings provide valuable information and confirm the position of the internal os of the cervix on MRI images, and the several important infuencing factors. We hope that some patients will benefit from our study.

Asunto(s)

Cuello del Útero , Imagen por Resonancia Magnética , Humanos , Femenino , Imagen por Resonancia Magnética/métodos , Cuello del Útero/diagnóstico por imagen , Cuello del Útero/patología , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Adulto , Histerectomía , Neoplasias Endometriales/diagnóstico por imagen , Neoplasias Endometriales/patología , Neoplasias Endometriales/cirugía , Útero/diagnóstico por imagen , Útero/patología , Útero/cirugía

RESUMEN

Uterine inflammation affects 8% of women in the United States and 32% in developing nations, often caused by uncontrolled inflammation and oxidative stress. This condition significantly impacts women's health, productivity, and quality of life, and increases the risk of related morbidities leading to higher healthcare costs. Research now focuses on natural antioxidants and anti-inflammatory, particularly berberine (BBR), an isoquinoline alkaloid known for its antioxidant, anti-inflammatory, and antiapoptotic activities. The present study sought to examine the potential therapeutic efficacy of BBR against uterine inflammation induced by the intrauterine infusion of an iodine (I2) mixture in an experimental setting. Female Sprague Dawley rats (n = 6) were divided into five groups, control, sham, I2, I2 and BBR 10 mg/kg, and I2 and BBR 25 mg/kg-treated groups. Compared to I2 infusion, BBR treatment effectively restored normal uterine histopathology and reduced inflammatory markers such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), nuclear factor- kappa B (NF-κB), monocyte chemoattractant protein 1 (MCP1), and myeloperoxidase (MPO). It lowered oxidative markers like malondialdehyde (MDA), and increased antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD). It balanced apoptotic genes by upregulating B-cell lymphoma 2 (Bcl-2) and downregulating Bcl-2-associated X protein (Bax). Furthermore, BBR reduced the expression of Toll-like receptor 2 (TLR-2), phosphorylated phosphatidylinositol 3­kinase (p-PI3K), and phosphorylated protein kinase B (p-AKT) in the rats treated with intrauterine I2. Ultimately, the therapeutic benefits of BBR can be attributed, to some extent, to its antioxidant, anti-inflammatory, and antiapoptotic properties, in addition to its ability to modulate the TLR-2/p-PI3K/p-AKT axis.

Asunto(s)

Antiinflamatorios , Berberina , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Ratas Sprague-Dawley , Transducción de Señal , Receptor Toll-Like 2 , Útero , Animales , Femenino , Berberina/farmacología , Berberina/uso terapéutico , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 2/genética , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Transducción de Señal/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Útero/efectos de los fármacos , Útero/patología , Útero/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Estrés Oxidativo/efectos de los fármacos , Apoptosis/efectos de los fármacos , Humanos , Citocinas/metabolismo , Inflamación/tratamiento farmacológico

RESUMEN

OBJECTIVE: To explore the utility of the total fibroids-to-uterine volume (FTUV) ratio as a simple, preoperative tool to assist in counseling patients seeking pregnancy who are undergoing myomectomy for intramural (IM) fibroids. STUDY DESIGN: This is an historical cohort study on reproductive-aged patients seeking pregnancy who underwent laparotomic myomectomy for intramural fibroids from January 2017 to December 2021. Only G3 to G5 fibroids, according to the 2011 International Federation of Gynecology and Obstetrics (FIGO) classification, were included. Pre-operative transvaginal ultrasound (TVUS) was performed to measure the volume of intramural myomas (diameter1*diameter2*diameter3*0.52) and to calculate their total volume. The total fibroids-to-uterine volume (FTUV) ratio was calculated as the proportion of the uterine volume occupied by the sum of IM fibroids volumes. RESULTS: A total of 166 women with pre-surgical TVUS evaluation of IM fibroids were included, with a mean age of 36.22 ± 5.15 years. The FTUV ratio was identified as a positive predictor of clinical pregnancy after surgery (adjOR, 1.04; 95 % CI, 1.02-1.06; p = 0.0001), whereas age showed a negative association (adjOR, 0.90; 95 % CI, 0.83-0.98; p = 0.012). Endometrial cavity distortion prior to surgery was also positively associated with pregnancy post-surgery (adjOR, 3.50; 95 % CI, 1.51-8.08; p = 0.003). Consistent results were found for live births, with the FTUV ratio being a significant positive predictor of live birth after surgery (adjOR, 1.03; 95 % CI, 1.01-1.05; p = 0.001) and age showing a negative association (adjOR, 0.88; 95 % CI, 0.80-0.96; p = 0.004). Parity prior to surgery also positively impacted live birth post-surgery (adjOR, 2.65; 95 % CI, 1.30-5.40; p = 0.007). An FTUV ratio threshold of 53.39 % accurately predicted clinical pregnancy in 68.46 % of cases (sensitivity of 71.70 % and specificity of 66.67 %). For live births, a higher FTUV ratio threshold of 59.21 % predicted outcomes accurately in 69.13 % of cases (sensitivity of 65.85 % and specificity of 70.37 %). CONCLUSION: The use of the FTUV ratio in pre-operative ultrasound evaluation of IM fibroids may improve counseling for patients desiring to conceive after myomectomy. By providing a personalized assessment of the amount of myometrial volume occupied by fibroids, the FTUV ratio can help predict fertility outcomes after surgery, enabling better-informed decisions and treatment planning.

Asunto(s)

Leiomioma , Miomectomía Uterina , Neoplasias Uterinas , Humanos , Femenino , Leiomioma/cirugía , Leiomioma/diagnóstico por imagen , Leiomioma/patología , Adulto , Neoplasias Uterinas/cirugía , Neoplasias Uterinas/patología , Neoplasias Uterinas/diagnóstico por imagen , Embarazo , Útero/diagnóstico por imagen , Útero/patología , Útero/cirugía , Tamaño de los Órganos , Ultrasonografía , Estudios de Cohortes

RESUMEN

BACKGROUND: Norethisterone acetate (NETA), also known as norethindrone acetate is a progestogens medication that is widely used in birth control pills, menopausal hormone therapy, and for the treatment of gynecological disorders as abnormal uterine bleeding and endometriosis. There is a lack of detailed histological information regarding the effects of NETA on the uterine structure. So, the present study focuses on the uterine histological, histochemical and ultrastructure changes following the exposure to NETA in the albino rats. To do this aim, fourteen adult female albino rats were used. They were randomly divided into two equally groups: Control group and NETA treated group. Albino rats of control group were administered daily food, water and orally distilled water only, while rats of NETA treated group were administered daily orally 20 µg of NETA dissolved in 2 ml distilled water, food, and water. The experiment was continued for three weeks. RESULTS: The findings of the present work indicated that the use of NETA has negative effects on the endometrial epithelium (proliferation, autophagy and apoptosis), glands (necrotic, apoptotic or pseudosecretory glands) and stromal and myometrial reactions (granulocytes, connective tissue remodeling, apoptosis, myocytes hypertrophy). CONCLUSION: This work revealed that NETA has desynchronized progestogenic effect on the uterine tissues of the albino rat and thereby prevent implantation and pregnancy.

Asunto(s)

Acetato de Noretindrona , Útero , Animales , Femenino , Útero/efectos de los fármacos , Útero/ultraestructura , Útero/patología , Ratas , Noretindrona/farmacología , Apoptosis/efectos de los fármacos , Endometrio/efectos de los fármacos , Endometrio/ultraestructura , Endometrio/patología

RESUMEN

INTRODUCTION: Uterus transplantation (UTx) is a novel treatment for absolute uterine infertility. Acute T cell-mediated rejection (TCMR) can be monitored only through serial cervical biopsies. METHODS: This study, the first of its kind in human transplantation, evaluated clinical, serological, and pathophysiological manifestations of allograft rejection from immunosuppression withdrawal (ISW) to graft hysterectomy (Hx). RESULTS: Following live birth, immunosuppression was abruptly withdrawn from six living-donor UTx recipients. ISW occurred at a median of 7.4 weeks before graft Hx. Post-ISW signs of rejection included: (1) discoloration of the cervix; (2) increased uterine size compared to day of ISW; (3) serological evidence of eosinophilia and progressive development of donor-specific antibodies (DSA) or child-specific antibodies (CSA); (4) histopathological evidence of TCMR in cervical biopsies preceding the development of antibodies in serum; and (5) C4d deposition in tissue before formation of DSA or CSA in all but two recipients. At graft Hx, endometrial glands were preferentially targeted for destruction over stroma while parametrial arteries displayed variable arteritis and fibrointimal hyperplasia. CONCLUSION: Recognition of the progression of uterine allograft rejection may be important for other human organ recipients and drive research on modulation of immunosuppression and the paradoxical relationship between adaptive cellular and humoral immunity in natural pregnancies. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02656550.

Asunto(s)

Rechazo de Injerto , Útero , Humanos , Femenino , Rechazo de Injerto/etiología , Rechazo de Injerto/patología , Rechazo de Injerto/inmunología , Útero/patología , Adulto , Estudios de Seguimiento , Pronóstico , Aloinjertos , Progresión de la Enfermedad , Supervivencia de Injerto/inmunología , Embarazo , Infertilidad Femenina/etiología , Infertilidad Femenina/cirugía , Complicaciones Posoperatorias , Factores de Riesgo

RESUMEN

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/genética

RESUMEN

In Brief: Advanced maternal age is associated with a higher rate of pregnancy complications that are unrelated to karyotypic abnormalities of the oocyte. This study shows that the murine uterine stroma undergoes profound epigenetic changes affecting active and repressive histone modification profiles that are associated with impaired endometrial functionality and underpin the decline in reproductive performance of aged females. Abstract: Decidualization describes the transformation of the uterine stroma in response to an implanting embryo, a process critical for supporting the development of the early embryo, for ensuring normal placentation and ultimately for a healthy reproductive outcome. Maternal age has been found to impede the progression of decidualization, heightening the risk of reproductive problems. Here, we set out to comprehensively characterize this deficit by pursuing transcriptomic and epigenomic profiling approaches specifically in the uterine stromal cell (UtSC) compartment of young and aged female mice. We find that UtSCs from aged females are globally far less responsive to the decidualization stimulus triggered by exposure to the steroid hormones estrogen and progesterone. Despite an overall transcriptional hyperactivation of genes that are differentially expressed as a function of maternal age, the hormonally regulated genes specifically fail to be activated in aged UtSCs. Moreover, even in their unstimulated 'ground' state, UtSCs from aged females are epigenetically distinct, as determined by genomic enrichment profiling for the active and repressive histone marks H3K4me3 and H3K9me3, respectively. We find that many hormone-inducible genes exhibit a profound lack of promoter-associated H3K4me3 in aged UtSCs, implying that a significant enrichment of active histone marks prior to gene stimulation is required to enable the elicitation of a rapid transcriptional response. With this combination of criteria, our data highlight specific deficits in epigenetic marking and gene expression of ion channels and vascular markers. These results point to fundamental defects in muscle-related and perivascular niche functions of the uterine stroma with advanced maternal age.

Asunto(s)

Envejecimiento , Decidua , Epigénesis Genética , Células del Estroma , Femenino , Animales , Ratones , Células del Estroma/metabolismo , Decidua/metabolismo , Decidua/patología , Código de Histonas , Histonas/metabolismo , Útero/metabolismo , Útero/patología , Embarazo , Reproducción , Ratones Endogámicos C57BL , Edad Materna

RESUMEN

In this surgical teaching video, we demonstrate the technique of robot-assisted uterine anastomosis combined with low anterior resection in a 27-year-old patient with T2 node-positive rectal cancer. The patient had undergone uterine transposition for fertility preservation prior to upfront chemotherapy and radiation therapy for rectal cancer. In this video, we review the key steps of both surgical procedures. We emphasize robot trocar placement and docking, demonstrate optimal organ manipulation and tissue handling, and include key operative modifications and pearls for successful perioperative management.

Asunto(s)

Anastomosis Quirúrgica , Neoplasias del Recto , Útero , Humanos , Femenino , Adulto , Anastomosis Quirúrgica/métodos , Útero/cirugía , Útero/patología , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , Preservación de la Fertilidad/métodos , Procedimientos Quirúrgicos Robotizados/métodos , Pronóstico

RESUMEN

INTRODUCTION: The non-perfused volume divided by total fibroid load (NPV/TFL) is a predictive outcome parameter for MRI-guided high-intensity focused ultrasound (MR-HIFU) treatments of uterine fibroids, which is related to long-term symptom relief. In current clinical practice, the MR-HIFU outcome parameters are typically determined by visual inspection, so an automated computer-aided method could facilitate objective outcome quantification. The objective of this study was to develop and evaluate a deep learning-based segmentation algorithm for volume measurements of the uterus, uterine fibroids, and NPVs in MRI in order to automatically quantify the NPV/TFL. MATERIALS AND METHODS: A segmentation pipeline was developed and evaluated using expert manual segmentations of MRI scans of 115 uterine fibroid patients, screened for and/or undergoing MR-HIFU treatment. The pipeline contained three separate neural networks, one per target structure. The first step in the pipeline was uterus segmentation from contrast-enhanced (CE)-T1w scans. This segmentation was subsequently used to remove non-uterus background tissue for NPV and fibroid segmentation. In the following step, NPVs were segmented from uterus-only CE-T1w scans. Finally, fibroids were segmented from uterus-only T2w scans. The segmentations were used to calculate the volume for each structure. Reliability and agreement between manual and automatic segmentations, volumes, and NPV/TFLs were assessed. RESULTS: For treatment scans, the Dice similarity coefficients (DSC) between the manually and automatically obtained segmentations were 0.90 (uterus), 0.84 (NPV) and 0.74 (fibroid). Intraclass correlation coefficients (ICC) were 1.00 [0.99, 1.00] (uterus), 0.99 [0.98, 1.00] (NPV) and 0.98 [0.95, 0.99] (fibroid) between manually and automatically derived volumes. For manually and automatically derived NPV/TFLs, the mean difference was 5% [-41%, 51%] (ICC: 0.66 [0.32, 0.85]). CONCLUSION: The algorithm presented in this study automatically calculates uterus volume, fibroid load, and NPVs, which could lead to more objective outcome quantification after MR-HIFU treatments of uterine fibroids in comparison to visual inspection. When robustness has been ascertained in a future study, this tool may eventually be employed in clinical practice to automatically measure the NPV/TFL after MR-HIFU procedures of uterine fibroids.

Asunto(s)

Aprendizaje Profundo , Ultrasonido Enfocado de Alta Intensidad de Ablación , Leiomioma , Neoplasias Uterinas , Humanos , Femenino , Leiomioma/diagnóstico por imagen , Leiomioma/terapia , Neoplasias Uterinas/diagnóstico por imagen , Neoplasias Uterinas/terapia , Ultrasonido Enfocado de Alta Intensidad de Ablación/métodos , Imagen por Resonancia Magnética/métodos , Adulto , Reproducibilidad de los Resultados , Carga Tumoral , Persona de Mediana Edad , Resultado del Tratamiento , Imagen por Resonancia Magnética Intervencional/métodos , Útero/diagnóstico por imagen , Útero/patología

RESUMEN

Uterine atony is a major contributor to postpartum hemorrhage. We previously proposed the novel histological concept of postpartum acute myometritis (PAM) to elucidate the pathophysiology of uterine atony. This concept involves the infiltration of macrophages and neutrophils, as well as mast cell and complement activation in the myometrium. However, the pathological mechanism underlying uterine atony in the context of PAM remains unclear. Herein, we focused on uterine contraction-associated proteins (CAPs) including connexin 43 (Cx43), oxytocin receptors (OXR), prostaglandin receptors EP1, EP3, FP, and protease-activated receptor (PAR)-1. This follow-up study aimed to compare CAP expression between PAM and control groups. We selected 38 PAM subjects from the cases enrolled in our amniotic fluid embolism registry between 2011 and 2018. Control tissues from 10 parturients were collected during cesarean section. We stained the myometrial tissues with the following CAP markers, inflammatory cell markers, and other markers: Cx43, OXR, EP1, EP3, FP, PAR-1, C5a receptor, tryptase, neutrophil elastase, CD68, ß-actin, and Na+/K+-ATPase. The immunostaining-positive areas of Cx43, OXR, EP1, EP3, and FP standardized by ß-actin in the PAM tissue were significantly smaller than in the control group, whereas those of PAR-1 and Na+/K+-ATPase increased significantly in the PAM group. The Cx43- and OXR-positive areas correlated negatively with the immunostaining-positive cell numbers of CD68 and tryptase with halo, respectively. PAM may impair individual and synchronized myocyte contraction, leading to uterine atony refractory to uterotonics. Further cell-based studies are needed to elucidate the molecular mechanism by which inflammatory cells suppress CAP expression.

Asunto(s)

Conexina 43 , Miometrio , Contracción Uterina , Humanos , Femenino , Embarazo , Miometrio/metabolismo , Miometrio/patología , Miometrio/inmunología , Adulto , Conexina 43/metabolismo , Receptores de Oxitocina/metabolismo , Inercia Uterina/metabolismo , Inercia Uterina/inmunología , Inercia Uterina/patología , Periodo Posparto/metabolismo , Receptor PAR-1/metabolismo , Útero/metabolismo , Útero/inmunología , Útero/patología , Enfermedad Aguda , Estudios de Seguimiento

RESUMEN

BACKGROUND: Ferroptosis is associated with the pathological progression of hemorrhagic injury and ischemia-reperfusion injury. According to our previous study, exosomes formed through bone marrow mesenchymal stem cells modified with miR-340-3p (MB-exos) can restore damaged endometrium. However, the involvement of ferroptosis in endometrial injury and the effect of MB-exos on ferroptosis remain elusive. METHODS: The endometrial injury rat model was developed. Exosomes were obtained from the supernatants of bone marrow mesenchymal stromal cells (BMSCs) and miR-340/BMSCs through differential centrifugation. We conducted RNA-seq analysis on endometrial tissues obtained from the PBS and MB-exos groups. Ferroptosis was induced in endometrial stromal cells (ESCs) by treating them with erastin or RSL3, followed by treatment with B-exos or MB-exos. We assessed the endometrial total m6A modification level after injury and subsequent treatment with B-exos or MB-exos by methylation quantification assay. We performed meRIP-qPCR to analyze m6A modification-regulated endogenous mRNAs. RESULTS: We reveal that MB-exos facilitate the injured endometrium to recover by suppressing ferroptosis in endometrial stromal cells. The injured endometrium showed significantly upregulated N6-methyladenosine (m6A) modification levels; these levels were attenuated by MB-exos through downregulation of the methylase METTL3. Intriguingly, METTL3 downregulation appears to repress ferroptosis by stabilizing HMOX1 mRNA, thereby potentially elucidating the mechanism through which MB-exos inhibit ferroptosis in ESCs. We identified YTHDF2 as a critical m6A reader protein that contributes to HMOX1 mRNA degradation. YTHDF2 facilitates HMOX1 mRNA degradation by identifying the m6A binding site in the 3'-untranslated regions of HMOX1. In a rat model, treatment with MB-exos ameliorated endometrial injury-induced fibrosis by inhibiting ferroptosis in ESCs. Moreover, METTL3 short hairpin RNA-mediated inhibition of m6A modification enhanced the inhibitory effect of MB-exos on ferroptosis in endometrial injury. CONCLUSIONS: Thus, these observations provide new insights regarding the molecular mechanisms responsible for endometrial recovery promotion by MB-exos and highlight m6A modification-dependent ferroptosis inhibition as a prospective therapeutic target to attenuate endometrial injury.

Asunto(s)

Exosomas , Ferroptosis , Hemo-Oxigenasa 1 , Células Madre Mesenquimatosas , MicroARNs , Animales , Femenino , Ratas , Adenosina/análogos & derivados , Adenosina/metabolismo , Endometrio/metabolismo , Endometrio/lesiones , Endometrio/patología , Exosomas/metabolismo , Ferroptosis/genética , Hemo Oxigenasa (Desciclizante) , Hemo-Oxigenasa 1/metabolismo , Hemo-Oxigenasa 1/genética , Células Madre Mesenquimatosas/metabolismo , Metiltransferasas/metabolismo , Metiltransferasas/genética , MicroARNs/genética , MicroARNs/metabolismo , Ratas Sprague-Dawley , Útero/metabolismo , Útero/lesiones , Útero/patología

RESUMEN

RATIONALE: Ichthyosis uteri is a rare pathological condition characterized by the replacement of the endometrial lining by stratified squamous epithelium. Yet its occurrence with endometrial adenocarcinoma is very rare. PATIENT CONCERNS: A 68-year-old woman has been experiencing sporadic, minor vaginal hemorrhages for a few months. The gynecological evaluation revealed a uterine enlargement and imaging demonstrated an irregular mass within the uterus. DIAGNOSIS: Endometrial adenocarcinoma with transitional cell differentiation; ichthyosis uteri with dysplasia. INTERVENTIONS: Radical hysterectomy with pelvic lymphadenectomy was performed followed by postoperative radiotherapy. OUTCOMES: Postoperative follow-up at 8 months showed a favorable outcome without signs of recurrence and metastasis. LESSONS: Adequate pathological sampling is crucial to identifying the accompanying lesions of ichthyosis uteri. Finding molecular alterations in various pathological morphologies is important to understand the evolution of disease.

Asunto(s)

Adenocarcinoma , Neoplasias Endometriales , Histerectomía , Ictiosis , Humanos , Femenino , Anciano , Neoplasias Endometriales/patología , Neoplasias Endometriales/complicaciones , Neoplasias Endometriales/cirugía , Adenocarcinoma/patología , Adenocarcinoma/complicaciones , Adenocarcinoma/cirugía , Ictiosis/patología , Ictiosis/complicaciones , Útero/patología

RESUMEN

BACKGROUND: Endometrial hyperplasia (EH) is a precursor to endometrial cancer, and the role of the microbiome in its development is unclear. RESULTS: The present study investigated the uterine microbiome in patients with benign uterine conditions and endometrial hyperplasia. A significant structural shift in the uterine microbiome of patients with endometrial hyperplasia compared to those with benign conditions was found. Delftia, Serratia and Stenotrophomonas were significantly enriched in endometrial hyperplasia samples and associated with the presence of endometrial hyperplasia. CONCLUSIONS: The novel finding suggested that increased abundance of Delftia, Serratia and Stenotrophomonas is associated with the presence of endometrial hyperplasia. Further investigation is needed to determine the value of these microbes as biomarkers for endometrial hyperplasia.

Asunto(s)

Bacterias , Hiperplasia Endometrial , Microbiota , Útero , Femenino , Humanos , Hiperplasia Endometrial/microbiología , Hiperplasia Endometrial/patología , Útero/microbiología , Útero/patología , Persona de Mediana Edad , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/genética , Adulto , ARN Ribosómico 16S/genética , Serratia/aislamiento & purificación , Serratia/genética , Serratia/patogenicidad , Stenotrophomonas/aislamiento & purificación , Stenotrophomonas/genética

RESUMEN

Endometritis is one of the important causes of infertility. Puerarin (PU) can inhibit oxidative stress and reduce inflammation; however, it is unclear whether PU has a protective effect on the endometritis. In our study, we used Staphylococcus aureus to induce mouse endometritis. The PU group (100 mg/kg PU) and the S. aureus + PU group received daily intraperitoneal injection of PU (25, 50 or 100 mg/kg PU). The results showed that S. aureus significantly increased the levels of MPO, TNF-α, IL-1ß and IL-6 in uterine tissue, and increased the expression of p-p65 and p-IκBα proteins in uterine tissue to induce endometritis in mice (p < 0.05). Furthermore, it has been found that S. aureus promotes the occurrence of ferroptosis by reducing GSH and ATP content, increasing MDA and iron content and reducing GPX4 and SLC7A11 protein expression levels (p < 0.05). S. aureus significantly increase the expression of NLRP3, ASC, caspase-1 and P2X7 proteins in uterine tissue (p < 0.05). However, PU obviously reduced the inflammatory response and reversed the changes of ferroptosis and the expression of P2X7 receptor/NLRP3 pathway associated proteins of the uterus induced by S. aureus (p < 0.05). Taken together, these findings emphasize the protective effect of PU on endometritis by regulating the P2X7 receptor/NLRP3 signalling pathway and inhibiting ferroptosis.

Asunto(s)

Endometritis , Ferroptosis , Isoflavonas , Proteína con Dominio Pirina 3 de la Familia NLR , Receptores Purinérgicos P2X7 , Transducción de Señal , Infecciones Estafilocócicas , Staphylococcus aureus , Animales , Femenino , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Isoflavonas/farmacología , Isoflavonas/uso terapéutico , Ferroptosis/efectos de los fármacos , Staphylococcus aureus/patogenicidad , Endometritis/metabolismo , Endometritis/microbiología , Endometritis/tratamiento farmacológico , Endometritis/patología , Transducción de Señal/efectos de los fármacos , Ratones , Receptores Purinérgicos P2X7/metabolismo , Infecciones Estafilocócicas/metabolismo , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/patología , Útero/metabolismo , Útero/patología , Útero/efectos de los fármacos , Útero/microbiología , Estrés Oxidativo/efectos de los fármacos

RESUMEN

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/terapia

RESUMEN

Polycystic ovary syndrome (PCOS) is the most common gynaecological, endocrine disorder that occurs during reproductive age and is a significant cause of anovulatory infertility. Letrozole is an aromatase inhibitor which negates the action of the aromatase enzyme, which results in the buildup of male hormones (testosterone) in the females, causing hyperandrogenism, which is a hallmark of Polycystic Ovarian Syndrome. Mifepristone (RU486) is a progestin antagonist that acts to arrest the actions of the progesterone hormone, resulting in follicular atresia and anovulation. DHEA is an androgen which was also administered in a bid to cause hyperandrogenism in the rats.This study aimed to evaluate the effects of these hormones on the cytoarchitecture of the ovaries and uterus to assess their various PCOS-like histological features.Animals were grouped mainly into three: Letrozole, Mifepristone and DHEA groups, which were further divided into two subgroups each, administered low and high doses of letrozole orally, Mifepristone and Dehydroepiandosterone (DHEA) subcutaneously. Each of the subgroups also had a comparison control group. Following the completion of administration, the Wistar rats were euthanized, and their ovaries and uterus were collected for histological analysis.Increased proliferation of ovarian follicles was noted in the treated groups compared to control, as well as thickening of the endometrial layer.

Asunto(s)

Modelos Animales de Enfermedad , Letrozol , Mifepristona , Ovario , Síndrome del Ovario Poliquístico , Ratas Wistar , Útero , Animales , Femenino , Síndrome del Ovario Poliquístico/patología , Síndrome del Ovario Poliquístico/inducido químicamente , Ratas , Letrozol/farmacología , Ovario/patología , Ovario/efectos de los fármacos , Mifepristona/farmacología , Útero/patología , Útero/efectos de los fármacos , Folículo Ovárico/efectos de los fármacos , Folículo Ovárico/patología , Folículo Ovárico/metabolismo , Deshidroepiandrosterona/farmacología

RESUMEN

OBJECTIVES: Despite regular gender-affirming hormone therapy (GAHT), the presence of uterine bleeding can occur occasionally and cause profound discomfort. This study aimed to evaluate the histologic features and immunohistochemical expression of estrogen (ER), progesterone (PR), and androgen receptors (AR) in the endometrium and myometrium of transgender men receiving testosterone therapy and relate them to clinical and hormonal characteristics. DESIGN: Retrospective cross-sectional study. METHODS: Thirty-four transgender men undergoing gender-affirming surgery were included. Clinical, sociodemographic, and laboratory data as well as anatomopathological and immunohistochemical findings were evaluated. RESULTS: The participants' mean age was 42.35 (SD, 10.00) years, and body mass index was 28.16 (SD, 5.52) kg/m2. The mean GAHT duration before surgery was 5.36 (SD, 3.24) years. The mean testosterone levels were 814.98 (SD, 407.13) ng/dL, and estradiol levels were 55.22 (SD, 25.27) pg/mL. The endometrium was atrophic in 61.8%, proliferative in 17.6%, and secretory in 20.6%. Immunohistochemical receptor analysis revealed that endometrial epithelial cells expressed ER (90%) and PR (80%), with a lower expression of AR (30%). In stromal tissue, the median ER, PR, and AR expression was lower than that in the epithelium (60%, 70%, and 25%, respectively). The myometrium showed high expression of PR (90%) and ER (70%), with the highest expression of AR (65%) being localized to this region. CONCLUSIONS: In the present study, GAHT induced an atrophic condition of the endometrium in two-thirds of the transgender men, with a limited AR expression in the endometrial region. The present results suggest that testosterone-based GAHT for a mean of 5 years is safe in transgender men achieving amenorrhea.

Asunto(s)

Endometrio , Receptores Androgénicos , Testosterona , Personas Transgénero , Humanos , Estudios Retrospectivos , Adulto , Estudios Transversales , Masculino , Femenino , Persona de Mediana Edad , Endometrio/efectos de los fármacos , Endometrio/metabolismo , Endometrio/patología , Receptores Androgénicos/metabolismo , Receptores de Progesterona/metabolismo , Útero/metabolismo , Útero/patología , Útero/efectos de los fármacos , Receptores de Estrógenos/metabolismo , Procedimientos de Reasignación de Sexo/efectos adversos , Miometrio/metabolismo , Miometrio/patología , Miometrio/efectos de los fármacos