Endometriosis Model Research Articles

Estrobolome dysregulation is associated with altered immunometabolism in a mouse model of endometriosis.

Endometriosis is a painful disease that affects around 5% of women of reproductive age. In endometriosis, ectopic endometrial cells or seeded endometrial debris grow in abnormal locations including the peritoneal cavity. Common manifestations of endometriosis include dyspareunia, dysmenorrhea, chronic pelvic pain and often infertility and symptomatic relief or surgical removal are mainstays of treatment. Endometriosis both promotes and responds to estrogen imbalance, leading to intestinal bacterial estrobolome dysregulation and a subsequent induction of inflammation. In the current study, we investigated the linkage between gut dysbiosis and immune metabolic response in endometriotic mice. Ovariectomized BALB/c mice received intraperitoneal transplantation of endometrial tissue from OVX donors (OVX+END). Control groups included naïve mice (Naïve), naïve mice that received endometrial transplants (Naive+END) and OVX mice that received the vehicle (OVX+VEH). Colonic content was collected 2 weeks post-transplantation for 16s rRNA pyrosequencing and peritoneal fluid was collected to determine the phenotype of inflammatory cells by flow cytometry. We noted a significant increase in the number of peritoneal fluid cells, specifically, T cells, natural killer (NK) cells, and NKT cells in OVX+END mice. Phylogenetic taxonomy analysis showed significant dysbiosis in OVX+END mice, with an increase in abundance of Phylum Tenericutes, Class Mollicutes, Order Aneroplasmatales, and Genus Aneroplasma, and a decrease in Order Clostridiales, and Genus Dehalobacterium, when compared to OVX+VEH controls. The metabolomic profile showed an increase in some tricarboxylic acid cycle (TCA)-related metabolites accompanied by a reduction in short-chain fatty acids (SCFA) such as butyric acid in OVX+END mice. Additionally, the mitochondrial and ATP production of immune cells was enforced to a maximal rate in OVX+END mice when compared to OVX+VEH mice. The current study demonstrates that endometriosis alters the gut microbiota and associated immune metabolism.

#296 : Identification and Validation of Two Novel Therapeutic Targets for Endometriosis with Artificial Intelligence (AI)

Background and Aims: It is urgent need to develop new-effective and well-tolerable medical treatment for endometriosis, but normal drug development is tedious, costly and time-consuming. Artificial intelligence (AI) is a powerful tool to drive discovery of novel druggable targets. Here we aim to use AI to identify novel therapeutic targets for endometriosis treatment. Method: Targets associated with endometriosis were prioritized by PandaOmics (a well-established AI-driven target identification platform). Expression levels of druggable targets were tested in human endometriotic lesions. Functional characterizations of the targets were performed by in-vitro and in-vivo endometriosis models. Viability, proliferation and apoptosis were examined. Results: Analysis of 11 public endometriosis bulk transcriptomics databases revealed 2 lists of high confidence and novel druggable targets. Tow novel targets ENDO01 and ENDO02 were selected based on ranking in PandaOmics, consistency of significant dysregulated expression across comparisons, as well as literature evidence relevant to disease-driving mechanisms. Differential expressions were confirmed in human endometriosis tissues. siRNA targeting ENDO01 and ENDO02 significantly reduced cell viability and proliferation, as well as enhanced apoptosis in endometriotic cells in-vitro; and significantly decreased lesion volume and weight with reduced proliferative and enhanced apoptosis in-vivo. Conclusion: Two novel targets for endometriosis were identified with AI and validated by in-vitro and in-vivo experiments within a short period. The study demonstrated how AI could speed up the novel target discovery process from years to months. For diseases remaining incurable or with high morbidity, the application of AI in target discovery could be a new therapeutic regimen that benefits patients.

Identification and Immune Characteristics Study of Pyroptosis‑Related Genes in Endometriosis.

Endometriosis (EMT) is a prevalent gynecological disorder characterized by pain and infertility associated with the menstrual cycle. Pyroptosis, an emerging cell death mechanism, has been implicated in the pathogenesis of diverse diseases, highlighting its pivotal role in disease progression. Therefore, our study aimed to investigate the impact of pyroptosis in EMT using a comprehensive bioinformatics approach. We initially obtained two datasets from the Gene Expression Omnibus database and performed differential expression analysis to identify pyroptosis-related genes (PRGs) that were differentially expressed between EMT and non-EMT samples. Subsequently, several machine learning algorithms, namely least absolute shrinkage selection operator regression, support vector machine-recursive feature elimination, and random forest algorithms were used to identify a hub gene to construct an effective diagnostic model for EMT. Receiver operating characteristic curve analysis, nomogram, calibration curve, and decision curve analysis were applied to validate the performance of the model. Based on the selected hub gene, differential expression analysis between high- and low-expression groups was conducted to explore the functions and signaling pathways related to it. Additionally, the correlation between the hub gene and immune cells was investigated to gain insights into the immune microenvironment of EMT. Finally, a pyroptosis-related competing endogenous RNA network was constructed to elucidate the regulatory interactions of the hub gene. Our study revealed the potential contribution of a specific PRG to the pathogenesis of EMT, providing a novel perspective for clinical diagnosis and treatment of EMT.

Effects of SU5416 on angiogenesis and the ERK-VEGF/MMP-9 pathway in rat endometriosis.

SU5416 is a small molecule vascular endothelial growth factor (VEGF) receptor signal transduction inhibitor, which can block the VEGF re-ceptor autophosphorylation and inhibit receptor tyrosine kinase signal trans-duction, thereby reducing VEGF activity. However, there are few reports about the correlation of SU5416 to the occurrence and angiogenesis in endometrio-sis. In this study, we observed the effects of VEGF receptor inhibitor SU5416 on angiogenesis in endometriosis in rats. Thirty femalespecific-pathogen-free Sprague-Dawley rats were randomly divided into sham operation group (SOG), model group (MG), and SU5416 group (n=10 for each group). In the SOG, only the uterus was cut and sutured, and endometriosis models were established in the MG and SU5416 group by autologous transplantation. The SU5416 group was injected with 15 mg/kg SU5416 intraperitoneally, and the SOG and MG were intraperitoneally injected with an equal volume of normal saline for 6 weeks. The volume of ectopic lesions was lower in the SU5416 group at 42 d postoperatively thanin the MG (p<0.05). The proportion of CD31-positive cells in the endometrial tissue of the SU5416 group was lower than that of the MG (p<0.05); angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), laminin-5γ2 (LN-5γ2) and phosphorylation of ERK (P-ERK), VEGF, matrix metalloproteinase (MMP)-2, and MMP-9 protein expressions were lower in the SU5416 groupthan in the MG (p<0.05).VEGFreceptor inhibitor SU5416 can inhibit endometrio-sis angiogenesis and reduce inflammatory response in rats, and its mechanism of action may be related to the down-regulation of the ERK-VEGF/MMP-9 path-way expression.

Identifying a panel of nine genes as novel specific model in endometriosis noninvasive diagnosis

To study biomarkers to develop a novel diagnosis model for endometriosis and validate it using clinical samples. We used publicly available data sets and weighted gene coexpression network analysis to identify differentially expressed genes. Ten machine learning algorithms were used to develop an integrative model for predicting endometriosis. The accuracy and robustness of the model were validated using data sets and clinical samples. Department of Obstetrics and Gynecology, Tangdu Hospital, Air Force Medical University, Xi'an, Shaanxi, China. The study included clinical patients between the ages of 20 and 40 years who required laparoscopic surgery and who had not undergone hormone therapy within the previous 3 months. All the healthy individuals had given birth to a child at least once in their lives. Patients with inflammatory conditions, malignant diseases, immune diseases, myoma, or adenomyosis were excluded. Paraffin blocks of the samples were collected (case, n = 5; control, n = 5). Blood samples of 58 individuals were collected (case, n = 28; control, n = 30). None. The areas under the receiver operator characteristic curve of our diagnostic model were measured for data sets and clinical samples. Multiplex immunohistochemical staining and real-time quantitative polymerase chain reaction assays were used for the validation of the model from tissue slides and peripheral blood samples. A nine-gene panel endometriosis messenger RNA score (EMScore), was constructed to distinguish the patients with endometriosis from healthy individuals using algorithms. The EMScore accurately predicted endometriosis, and the areas under the receiver operator characteristic curve of our diagnostic model were 0.920, and 0.942 for tissue and blood samples, respectively. Moreover, the EMScore outperformed other acknowledged signatures for predicting endometriosis across seven clinical cohorts. Overall, the EMScore constitutes a sensitive and specific noninvasive diagnostic method for endometriosis. We developed the EMScore, a novel model that can aid in the diagnosis of endometriosis using peripheral blood samples. This study will contribute to the development of improved clinical noninvasive and sensitive diagnostic tools for endometriosis. These nine genes might be potential target molecules for treating endometriosis.

Differential expression of interleukin-35 receptor distinguishes different subsets of granulocyte-macrophage-colony-stimulating factor-producing T helper cells in a mouse endometriosis model

The immune system contributes to the pathophysiology of endometriosis. The role of ThGM cells, which produce granulocyte macrophage-colony-stimulating factor (GM-CSF), in the pathogenesis of endometriosis remains unknown. To analyze the features of ThGM cells in endometriosis, a mouse endometriosis model was established. ThGM cells in the spleen, peritoneal fluid (PF), and endometriotic lesions (EL) were measured by flow cytometry, based on the expression of surface markers and intracellular proteins. Live ThGM cells were sorted according to chemokine receptor expression profiles and their effects on other CD4+ T cell subsets were determined by co-culture assays. An adoptive transfer assay was performed to characterize the effect of ThGM cells on endometriosis. We found that ThGM cells were present in endometriotic PF and EL. Live EL ThGM cells were enriched in CD4+CXCR3-CCR8-CCR4+CCR10+ T cells. EL ThGM cells differentially express interleukin-35 receptor (IL-35R), consisting of an IL-35R+ subset and an IL-35R- subset. The IL-35R+ subset expressed less GM-CSF, interleukin-2 (IL-2), and tumor necrosis factor-alpha (TNF-α) and proliferated slower than the IL-35R- subset. Meanwhile, the IL-35R+ subset was weaker than the IL-35R- subset in promoting the functions of Th1 and Th17 cells. ThGM cell transfer did not influence EL development but significantly alleviated pro-inflammatory cytokines in PF and ELs. Interleukin-35 (IL-35), the ligand of IL-35R, suppressed ThGM cell function and proliferation in an IL-35R-dependent manner. In summary, ThGM cells in the PF and ELs might exacerbate endometriotic inflammation. IL-35 might suppress the function of ThGM cells via IL-35R.

The Effect of Flavonoid from Extract of Phaleria Macrocarpa on Levels Il-2, Il-17a and Il-33 in Endometriosis Mice

Endometriosis is a inflamatory disease especially in the state of reproductive age. Phaleria macrocarpa is a plant that has a population in Papua, Irian Jaya. Endometriosis therapies available have still many weakness, including being expensive, only relieving pain, and continuous treatment to prevent endometriosis from recurring. The fruit and seeds of the Phaleria macrocarpa have a wide range of important biological activities in the form of extracts such as antimicrobial, anti-inflammatory, and antioxidant activities. This aim of this was to analyze the effect of flavonoid from extract of phaleria macrocarpa on IL-2, IL-17A, and IL-33 levels in endometriosis mice. This research is using total of 40 female mice (Mus musculus) model endometriosis were grouped into 8 groups, including of healthy mice (without any treatment), the endometriosis group, and the endometriosis group treated flavonoids of Phaleria macrocarpa with dose of 3.75 mg/day; 7.5 mg/day; 11.2 mg/day; 15 mg/day. The level of IL-2, IL-17A, IL-33 were measured using the ELISA method. There was an increase in IL-2, IL-33, and IL17A levels in mice model of endometriosis. Flavonoid of Phaleria macrocarpa can reduce levels of proinflammatory cytokines such as IL-2, IL-33, and IL17A.

A protocol for creating endometriosis in rhesus macaques (Macaca mulatta).

Endometriosis is the presence of endometrium-like tissue outside the uterine cavity. An experimental model of endometriosis has been created in the baboon by the transcervical collection and laparoscopic inoculation of menstrual endometrium. Macaques are the preferred model for pharmaceutical development, but the complex anatomy of the macaque cervix makes the baboon method impractical. In this work, we sought to validate a surgical approach for creating endometriosis in macaques. Menstrual endometrium was collected via laparoscopic intrauterine puncture and transferred to the peritoneal cavity. We repeated this procedure during three menstruations. Endometriotic tissue was identified during laparoscopy, collected, and characterized by immunohistochemistry. Sham surgery-treated animals (n = 3) failed to develop endometriosis. We identified red, powder burnt, and white lesions in 13/14 of the treated animals; the stroma of the red lesions stained positive for ovarian steroid receptors. This surgical technique can reliably create hormone-responsive endometriosis in macaques for therapeutic studies.

Macrophages originated IL-33/ST2 inhibits ferroptosis in endometriosis via the ATF3/SLC7A11 axis

Endometriosis is a gynecological inflammatory disease that is linked with immune cells, specifically macrophages. IL-33 secreted from macrophages is known to accelerate the progression of endometriosis. The periodic and repeated bleeding that occurs in women with endometriosis leads to excess iron in the microenvironment that is conducive to ferroptosis, a process related to intracellular ROS production, lipid peroxidation and mitochondrial damage. It is suggested that eESCs may specifically be able to inhibit ferroptosis. However, it is currently unclear whether IL-33 directly regulates ferroptosis to influence the disease course in endometriosis. In this study, eESCs co-cultured with macrophages or stimulated with IL-33/ST2 were observed to have increased cell viability and migration. Additionally, IL-33/ST2 decreased intracellular iron levels and lipid peroxidation in eESCs exposed to erastin treatment. Furthermore, IL-33/ST2 treatment resulted in a notable upregulation in SLC7A11 expression in eESCs due to the downregulation of negative transcription factor ATF3, thereby suppressing ferroptosis. The P38/JNK pathway activated by IL-33/ST2 was also found to inhibit the transcription factor ATF3. Therefore, we concluded that IL-33/ST2 inhibits the ATF3-mediated reduction in SLC7A11 transcript levels via the P38/JNK pathway. The findings reveal that macrophage-derived IL-33 upregulates SLC7A11 in eESCs through the p38/JNK/ATF3 pathway, ultimately resulting in protection against ferroptosis in eESCs. Moreover, we conducted an experiment using endometriosis model mice that showed that a combination of IL-33-Ab and erastin treatment alleviated the disease, showing the promise of combining immunotherapy and ferroptosis therapy.

Efficacy of an environmental enrichment intervention for endometriosis: a pilot study.

We have previously shown that Environmental Enrichment (EE), a multi-modal psychosocial intervention consisting of increased social interaction, novelty, and open spaces, improved disease presentation, anxiety, and immune-related disturbances in the rat model of endometriosis. However, there is a knowledge gap regarding the effects of EE interventions in patients with this painful, inflammatory chronic disease. To adapt and test the efficacy of an EE intervention on pelvic pain, mental health, perceived stress, quality of life, and systemic inflammation in endometriosis patients through a randomized clinical trial (RCT). A multidisciplinary team with expertise in physiology, neuroscience, psychology, and women's health adapted and implemented a two-arm RCT comparing an EE intervention with a wait-list control group. Six EE modules administered on alternate weeks were provided to patients in the intervention (N = 29); controls received education only. Survey data and biospecimens were collected at baseline, end-of-study, and 3-months post-intervention to assess pain (Brief Pain Inventory, BPI), endometriosis-related quality of life-QoL (Endometriosis Health Profile-30, EHP30), anxiety (Generalized Anxiety Disorder 7, GAD7), depression (Patient Health Questionnaire for Depression 8, PHQ8), pain catastrophizing (Pain Catastrophizing Score, PCS), stress (Perceived Stress Scale-14, PSS14), and saliva cortisol levels (AM, PM). Compared to the wait-list controls, participants in the EE intervention showed significantly decreased GAD-7 scores at the end of the intervention and 3-month follow-up. Depression, perceived stress, and QoL improved at the 3-month follow-up compared to baseline. While pain levels did not improve, they significantly correlated with anxiety, depression, QoL and pain catastrophizing scores. This pilot RCT demonstrated significant improvements in anxiety and depressive symptoms, QoL, and perceived stress, supporting enriched environments as an integrative psychosocial intervention to be used as adjuvant to the standard of care for endometriosis pain.

Feel so bac: is Fusobacterium the suspect causing endometriosis?

Recent work by Muraoka and colleagues reports that the Gram-negative anaerobic bacterium Fusobacterium nucleatum is detected in the uterus of 64% of women with endometriosis. Fusobacterium infection causes macrophage infiltration, transforming growth factor-β production, and transgelin upregulation in human and mouse endometria as well as endometriotic lesion development in a mouse model of endometriosis.

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

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

Extracellular ATP (eATP) inhibits the progression of endometriosis and enhances the immune function of macrophages

BackgroundExtracellular adenosine triphosphate (eATP) is an important inflammatory mediator that can boost the antitumour immune response, but its role in endometriosis remains unknown. We hypothesized that eATP could inhibit endometriosis cell function both directly and indirectly through macrophages. MethodsPeritoneal and cyst fluid from endometriosis patients and non-endometriosis controls was collected to measure eATP levels. The addition of eATP was performed to explore its effects on endometriotic cell and macrophage functions, including cell proliferation, apoptosis, pyroptosis, mitochondrial membrane potential, phagocytosis, and the production of inflammatory cytokines and reactive oxygen species. A coculture of endometriotic epithelial cells and U937 macrophages was established, followed by P2X7 antagonist and eATP treatment. Endometriosis model eATP-treated rats were used to evaluate in situ cell death and macrophage marker expression. ResultsThe pelvic microenvironment of endometriosis patients shows high eATP levels, which could induce endometriotic epithelial cell apoptosis and pyroptosis and significantly inhibit cell growth via the MAPK/JNK/Akt pathway. eATP treatment ameliorated endometriosis-related macrophage dysfunction and promoted macrophage recruitment. eATP treatment in the presence of macrophages exerted a stronger cytotoxic effect on endometriotic epithelial cells by regulating P2X7. eATP treatment effectively induced cell death in an endometriosis rat model and prominently increased the macrophage number without affecting the eutopic endometrium. ConclusioneATP induces endometriotic epithelial cell death and enhances the immune function of macrophages to inhibit the progression of endometriosis, while eutopic endometrium is not affected. eATP treatment may serve as a nonhormonal therapeutic strategy for endometriosis.

Sulawesi propolis induces higher apoptotic activity and lower inflammatory activity in a rat endometriosis model.

Endometriosis has a major impact on women's quality of life. The two primary pathologies are chronic inflammation and altered apoptotic activity. Sulawesi propolis has been shown to have known anti-inflammatory and pro-apoptotic properties in other diseases. To investigate the effects of Sulawesi propolis in the rat endometriosis model. An autologous endometriosis model was created in 60 female Wistar rats by laparotomy. Rats were divided into four groups (n=15 in each group): control group (CG), dienogest group (DG), propolis 50mg/kg body weight (BW)/day (P50) group, and propolis 100mg/kg BW/day (P100) group. Each treatment group was divided into three different treatment durations (n=5 in each treatment group): 2, 4 and 6 weeks. After treatment, laparotomy was performed to determine endometriotic tissue growth, apoptosis [caspase-3 and Bcl-2-associated X/Bcl-2 (Bax/Bcl)] and inflammation [prostaglandin-E2 (PGE2) and interleukin-1B (IL-1B)]. A significant difference was seen in endometriotic tissue growth between the P50 group and the CG, with the greatest reduction in the P50 6-week (P50-6) group, reaching 70.66% of the initial area. Highest Bax/Bcl-2 mRNA expression was shown in the P50-4 and P100-4 groups, highest caspase-3 expression was shown in the P50-2 and P50-4 groups, and lowest IL-1B expression was shown in the P50-4 group; all differed significantly from the CG. No significant difference in PGE2S mRNA was found between the groups. Sulawesi propolis extract suppressed endometriotic tissue growth in the rat model by increasing apoptotic activity. The effects were time-dependent, with 50mg/kg BW as the optimal dose.

Cystic tumor ablation with different concentrations of lauromacrogol solution in an animal model.

Lauromacrogol, as a sclerosing agent, can induce aseptic inflammation and fibrous tissue proliferation to achieve sclerotherapy. Lauromacrogol is widely used not only for vascular sclerotherapy but also for the treatment of different cystic tumors. To evaluate the efficacy and safety of cystic tumor ablation with different concentrations of lauromacrogol solution in a rat endometriosis model, and explore the advantages and disadvantages of this model in simulating pancreatic cystic neoplasm. An endometriotic cyst model was established in 50 mature female Sprague-Dawley rats. After 4 weeks, successfully modeled cysts were randomly divided into four groups: group A, in which cyst were injected with normal saline; and groups B to D, in which cyst were injected with 1%, 2%, and 3% lauromacrogol solution, respectively. The rats were then fed for 4 more weeks. The abdominal cavity was opened to observe the morphology of the cyst and the degree of damage to surrounding organs. If the ablation procedure failed, the whole cyst was collected; if the ablation procedure was successful, residual scar tissue was collected. The ratio of ablated epithelial cells to the epithelial layer and the intactness of the lamina propria were observed by low- and high-power microscopy. After ablation, the cysts in normal saline group showed a maintained hemispherical structure, whereas those in three different concentrations of lauromacrogol solution groups showed a flat scar. The effective rate of each group was statistically different. Pairwise comparison of corrected significance levels using the Bonferroni method showed statistically a significant difference between normal saline group and 1% lauromacrogol solution group, 2% lauromacrogol solution group and 3% lauromacrogol solution group. According to the morphology and pathology of rat endometriotic cysts after ablation, it can be preliminarily concluded that ablation with 1%, 2%, or 3% lauromacrogol solution is an effective and safe therapeutic option. Rat endometriotic cyst model can simulate pancreatic cystic neoplasms to a certain extent.

Effects of dysregulated glucose metabolism on the occurrence and ART outcome of endometriosis

BackgroundEndometriosis is associated with systemic metabolic indicators, including body mass index (BMI), glucose metabolism and lipid metabolism, while the association between metabolic indexes and the occurrence and assisted reproductive technology (ART) outcome of endometriosis is unclear. We aimed to evaluate the characteristics of systemic metabolic indexes of endometriosis patients with infertility and their effects on pregnancy outcome after ART treatment.MethodsA retrospective cohort study involve 412 endometriosis patients and 1551 controls was conducted. Primary outcome was metabolic indexes, and secondary measures consisted of the influence of metabolic indexes on the number of retrieved oocytes and ART outcomes.ResultsEndometriosis patients had higher insulin (INS) [6.90(5.10–9.50) vs 6.50(4.80–8.90) μU/mL, P = 0.005]. A prediction model for endometriosis combining the number of previous pregnancies, CA125, fasting blood glucose (Glu) and INS, had a sensitivity of 73.9%, specificity of 67.8% and area under curve (AUC) of 0.77. There were no significant differences in ART outcomes and complications during pregnancy. The serum levels of Glu before pregnancy were associated with GDM both in endometriosis group (aOR 12.95, 95% CI 1.69–99.42, P = 0.014) and in control group (aOR 4.15, 95% CI 1.50–11.53, P = 0.006).ConclusionsWe found serum Glu is related to the number of retrieved oocytes in control group, serum INS is related to the number of retrieved oocytes in endometriosis group, while serum Glu and INS before pregnancy are related to the occurrence of GDM in two groups. A prediction model based on metabolic indexes was established, representing a promising non-invasive method to predict endometriosis patients with known pregnancy history.

The Effects of Vitamin D3 Supplementation and Simultaneous Exercise on Aldehyde Dehydrogenase Gene Expression in Endometriosis Female Rats

Background: Endometriosis is an injury caused by the proliferation of endometrial tissue outside the uterine cavity. Exercise and supplements may effectively remove waste materials and produce antioxidant enzymes. Objectives: The present research aimed to investigate the effects of simultaneous exercise and vitamin D3 supplement on aldehyde dehydrogenase 2 (ALDH2A1) gene expression in endometriosis female rats. Methods: The experimental method with a post-test design was used to conduct the research. The statistical population of the study consisted of three-month-old female Wistar rats. After the induction of the endometriosis model, the rats were divided into six groups. The exercise groups performed simultaneous exercises for eight weeks. Vitamin D3 supplement at 50 mg was fed to rats daily for eight weeks. The mean and standard deviation of ALDH2A values were calculated, and two-way analysis of variance (ANOVA) and Bonferroni post hoc test were investigated in female rats in different groups (P

Comparison of the Effects of Dienogest and Leuprolide Acetat on Serum Interferon (IFN-Ɣ) Levels in a Mouse Model of Endometriosis (Mus musculus)

Introduction: Endometriosis is a medical condition in which there is abnormal growth of tissue resembling the endometrium outside the uterus. It can cause symptoms of pain and/or infertility. The current medical therapy focuses on reducing estradiol levels or stimulating progesterone response. One of the most effective options for medical treatment is the use of GnRH analogs. Dienogest have a direct anti-inflammatory effect on endometriotic stromal cells. However, a comparison of the anti-inflammatory effects of these drugs on IFN-Ɣ has not been previously investigated. Therefore, this study aims to compare the effects of reducing IFN-Ɣ by both Dienogest and Leuprolide Acetat in a mouse model. Material and Methods: This study employed a post-test only control group design and involved 4 groups, namely the negative control group, positive control group, and two treatment groups: one group administered Dienogest at a dosage of 0.0052 milligrams per day for 14 days, and the other administered Leuprolide Acetat at a dosage of 0.00975 milligrams once every 5 days for a period of 14 days. Serum IFN-Ɣ levels were measured using Enzyme-Linked Immunosorbent Assay (ELISA). The data were subsequently analyzed using IBM SPSS 25 with One-Way ANOVA test. Results: This study demonstrated that Leuprolide Acetat significantly decreased serum levels of IFN-Ɣ, whereas Dienogest actually increased the levels . Conclusion: In a mouse model of endometriosis (Mus musculus), Leuprolide Acetat effectively reduced the levels of IFN-Ɣ (pro-inflammatory). Conversely, Dienogest increased the levels of IFN-Ɣ (anti-inflammatory) in the mouse model of endometriosis.

IRGD-Targeted Peptide Nanoparticles for Anti-Angiogenic RNAi-Based Therapy of Endometriosis.

Anti-angiogenic RNAi-based therapy can be considered as a possible strategy for the treatment of endometriosis (EM), which is the most common gynecological disease. Targeted delivery of siRNA therapeutics is a prerequisite for successful treatment without adverse effects. Here we evaluated the RGD1-R6 peptide carrier as a non-viral vehicle for targeted siRNA delivery to endothelial cells in vitro and endometrial implants in vivo. The physicochemical properties of the siRNA complexes, cellular toxicity, and GFP and VEGFA gene silencing efficiency were studied, and anti-angiogenic effects were proved in cellular and animal models. The modification of siRNA complexes with iRGD ligand resulted in a two-fold increase in gene knockdown efficiency and three-fold decrease in endothelial cells' migration in vitro. Modeling of EM in rats with the autotransplantation of endometrial tissue subcutaneously was carried out. Efficiency of anti-angiogenic EM therapy in vivo by anti-VEGF siRNA/RGD1-R6 complexes was evaluated by the implants' volume measurement, CD34 immunohistochemical staining, and VEGFA gene expression analysis. We observed a two-fold decrease in endometriotic implants growth and a two-fold decrease in VEGFA gene expression in comparison with saline-treated implants. RNAi-mediated therapeutic effects were comparable with Dienogest treatment efficiency in a rat EM model. Taken together, these findings demonstrate the advantages of RGD1-R6 peptide carrier as a delivery system for RNAi-based therapy of EM.

Effects of Quince Gel and Hesperidin Mixture on Experimental Endometriosis.

Endometriosis (EM) is the presence of endometrial tissue outside the uterus. This study aimed to examine the effects of quince gel and hesperidin treatment on uterine tissue in an experimental endometriosis model. Thirty-two rats were categorized into four groups as sham, EM, EM+quince gel (QG), and EM+QG+Hesperidin (HES). The endometriosis (EM) model was induced with surgical intervention. Estradiol benzoate (EB) was used to induce endometrial hyperplasia. In the EM group, EB was given to rats for 7 days. The EM+QG group received 2 cc QG for 21 days. HES treatment was given for 21 days after EM induction. At the end of the experiment, blood was taken from the animals and the serum total antioxidant status (TAS) and total oxidant status (TOS) values were studied. Uterine tissues were dissected and processed for histological paraffin embedding. Tissues were fixed in 4% glutaraldehyde solution and processed for ultrastructural analysis. After EM, QG and HES treatment significantly increased the TAS and decreased the TOS value. EM caused epithelial and glandular degeneration, thinning of the basal membranes, and vascular dilatation with increased fibrosis and edema. QG+HES restored the pathology and showed protective effects in uterine tissues. Caspase-3 expression was increased in the epithelium, glands, and muscle layers of the EM group. In EM+QG+HES, hesperidin protected cell survival and decreased Caspase-3 expression in uterine tissues. TNF-α expression was intense in inflammatory cells and the muscle layer in the EM group. HES reduced inflammation by decreasing the TNF-α expression. MAPK expression was increased after EM induction in epithelial, glandular, and inflammatory cells in the EM group. After HES treatment, MAPK expression was mainly negative in cells of uterine tissue in the EM+QG+HES group. Ultrastructurally, in the EM group, organelles were disrupted and dilated and degenerated after EM induction. QG and HES treatment improved cellular organelles. Local vaginal applications can be an alternative treatment method in the endometriosis model via QG+HES treatment promoting cell proliferation and angiogenesis and preventing cell death.