Induction Of Endometriosis Research Articles

High‐Intensity Interval Training Enhances the Positive Effect of Pentoxifylline on Lipid Profile and Inflammatory Markers in an Endometriosis Animal Model

Background: The relationship between endometriosis and cardiovascular disease (CVD) is well established. However, the effects of various exercise training modalities and the anti‐inflammatory effects of pentoxifylline (PTX) remain inadequately understood. This investigation is aimed at evaluating the effects of PTX, both independently and in conjunction with high‐intensity interval training (HIIT) and moderate‐intensity continuous training (MICT), on lipid and inflammatory markers including triglycerides (TGs), total cholesterol (TC), high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), and C‐reactive protein (CRP) in a rat model of endometriosis.Materials and Methods: Sprague–Dawley’s rats were divided into two primary groups: the healthy control group that received no intervention and the induced endometriosis group. Endometriosis was surgically induced in rats, and those with confirmed endometriotic lesions were further categorized into six groups: control, MICT, drug of PTX (D), MICT+D, HIIT, and HIIT+D. Two weeks after laparotomy, PTX consumption and exercise training were performed for 8 weeks. PTX was administered orally at 100 mg/kg/day. MICT and HIIT sessions were conducted 5 days per week, with MICT beginning at 55% of maximum capacity for 31 min in the first week and progressing to 70% of maximum capacity for 46 min by the eighth week. HIIT sessions consisted of 2 min of running followed by 1 min of passive rest at 85% of maximum capacity, starting with seven intervals in the first week and increasing to twelve by the end of the eighth week. The macroscopic size of endometriosis lesions was measured, and cardiovascular risk factors, including hs‐CRP, TC, TG, HDL‐C, and LDL‐C, were assessed in serum samples.Results: The induction of endometriosis was associated with elevated cardiovascular risk factors, including hs‐CRP, TC, and TG. HIIT+D significantly decreased lesion volume (p < 0.0001, 95%confidence interval (CI) = 57.239–94.718), hs‐CRP (p = 0.049, CI = −54.083 to − 29.478), TC (p = 0.045, CI = −38.607 to − 25.392), and TG (p = 0.042, CI = 25.531–55.801). PTX significantly decreased lesion volume (p < 0.0001, CI =34.709–73.919) and TC (p = 0.016, CI = −45.153 to − 30.179).Conclusion: All interventions except MICT reduced lesion volume, whereas only HIIT+PTX and PTX, in the order of importance, improved some cardiovascular risk indices in the rat model of endometriosis.

Thymol Impacts the Progression of Endometriosis by Disrupting Estrogen Signaling Pathways and Inflammatory Responses.

Endometriosis is a chronic inflammatory, estrogenic disorder caused by endometrial tissue growth places other than uterine lumen, resulting in infertility and severe pelvic pain. Thymol, an extract of Thymus vulgaris, processes diverse biological properties, including anti-inflammatory, local anesthetic, decongestant, and antiseptic effects. However, the efficacy of thymol in treating endometriosis has still not been explored. Herein, this research aimed to investigate the role of thymol in the treatment of endometriosis using a murine model and Ishikawa cells. Thirty C57BL/6 mice were administered 17β-E2 (100 ng/mouse) subcutaneously for three consecutive days to induce synchronous estrus. On the last day of injection, the mice underwent surgical induction of endometriosis. After that, the mice were divided into three groups, i.e., Control (CTRL), Thymol 30 mg/kg and Thymol 60 mg/kg, receiving oral administration of either saline or thymol (30 mg/kg/d or 60 mg/kg/d, as 0.1 mL/kg/d, respectively) for a three-week duration. Each group consisted of ten mice and was evenly divided into estrus and diestrus according to the vaginal cytology on the last day of treatment. Thymol significantly (p < 0.05) reduced the weight and volume of ectopic tissue, hindered cell proliferation, and stimulated apoptosis compared to the CTRL group. Additionally, in the thymol-treated group, the levels of pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6, as well as the numbers of neutrophils and macrophages, were significantly (p < 0.05) decreased. Moreover, a novel role of thymol in rebalancing estrogen and progesterone (E2-P4) signaling was explored, and it was distributed in the ectopic endometrium. Next, the role of thymol on Ishikawa cells was determined. The results demonstrated that thymol significantly (p < 0.05) suppressed the E2-induced proliferation of Ishikawa cells. Furthermore, molecular docking analyses suggested that thymol potentially binds to ESR1-like estrogens, indicating its antagonistic activity against estrogens. The estrogen receptor 1 (ESR1) and its target gene expression exhibited significant (p < 0.05) downregulation, while progesterone receptor (PGR) and target genes were markedly (p < 0.05) upregulated following thymol treatment in the ectopic endometrium. Most importantly, our data revealed the minimal impact of thymol treatment on the eutopic endometrium and its crucial role in supporting pregnancy, thus indicating the safety of thymol in treating endometriosis. Overall, our study suggests that thymol holds promising therapeutic implications for endometriosis by virtue of its anti-inflammatory properties and ability to antagonize estrogen activity.

Western diet promotes endometriotic lesion growth in mice and induces depletion of Akkermansia muciniphila in intestinal microbiota.

Endometriosis, affecting 10% of women in their reproductive years, remains poorly understood. Both individual and environmental unexplained factors are implicated in this heterogenous condition. This study aims to examine the influence of a Western diet on endometriosis lesion development in mice and to uncover the mechanisms involved. Mice were fed either a control diet or a Western diet (high in fatty acids and low in fiber) for 4weeks. Endometriosis was then surgically induced, and lesion development was monitored by ultrasound. After 7weeks, the mice were sacrificed for analysis of lesion characteristics through RT-qPCR, immunohistochemistry, and flow cytometry. Additionally, the intestinal microbiota was assessed using 16S rRNA gene sequencing. Mice on the Western diet developed lesions that were significantly twice as large compared to those on the control diet. These lesions exhibited greater fibrosis and proliferation, alongside enhanced macrophage activity and leptin pathway expression. Changes in the intestinal microbiota were significantly noted after endometriosis induction, regardless of diet. Notably, mice on the Western diet with the most substantial lesions showed a loss of Akkermansia Muciniphila in their intestinal microbiota. A Western diet significantly exacerbates lesion size in a mouse model of endometriosis, accompanied by metabolic and immune alterations. The onset of endometriosis also leads to substantial shifts in intestinal microbiota, suggesting a potential link between diet, intestinal health, and endometriosis development.

M6A methylation of RNF43 inhibits the progression of endometriosis through regulating oxidative phosphorylation via NDUFS1.

Oxidative phosphorylation is becoming increasingly important in the induction and development of endometriosis. Recently, it has been reported that ring finger protein 43 (RNF43) is involved in the process of oxidative phosphorylation, but the mechanism remains unclear. Our investigation is to delve into the roles of RNF43 in endometriosis and elucidate the related mechanisms. We found RNF43 was downregulated in ectopic endometrial tissue and primary ectopic endometrial stromal cells (ECESCs). Knockdown of RNF43 enhanced cell viability and migration by activating oxidative phosphorylation in eutopic endometrial stromal cells (EUESCs), while overexpression of RNF43 led to the opposite results. Moreover, RNF43 reinforced the ubiquitination and degradation of NADH dehydrogenase Fe-S protein 1 (NDUFS1) by interacting with it. Likewise to RNF43 overexpression, NDUFS1 silencing inhibited cell viability, migration, and oxidative phosphorylation in ECESCs. NDUFS1 was a downstream target of RNF43, mediating its biological role in endometriosis. Interestingly, the expression and stability of RNF43 mRNA were regulated by the Methyltransferase-like 3 (METTL3)/IGF2BP2 m6A modification axis. The results of rat experiments showed decreased RNF43 expression and increased NDUFS1 expression in endometriosis rats, which was enhanced by METTL3 inhibition. Those observations indicated that m6A methylation-mediated RNF43 negatively affects viability and migration of endometrial stromal cells through regulating oxidative phosphorylation via NDUFS1. The discovery of METTL3/RNF43/NDUFS1 axis suggested promising therapeutic targets for endometriosis.

#19 : Green Tea Extract Inhibits Endometriosis Progression by Increasing Superoxide Dismutase Serum Levels in the Rat Models

Background and Aims: Endometriosis is a gynecological disorder defined as the presence of endometrial tissue outside the uterine cavity and affecting 10-15% of females of reproductive age. Oxidative stress has been reported as one of the main promoting factors of this disease. Green tea and its anti-angiogenic and antioxidant properties have promising potential to prevent the progression of endometriosis. This study aims to investigate the effect of green tea extract on endometriotic implant area and serum superoxide dismutase (SOD) levels in endometriosis rat models. Method: Twenty-six Balb/c female rats were randomized into two groups of equal size: experimental group (EG) and control group (CG). All subjects in EG were given green tea extract 3 mg daily for 14 days. Endometriosis was induced on the fourteenth day in all subjects in both groups. The data of the endometriotic implant area and serum SOD were obtained and analyzed fourteen days after the induction of endometriosis. Results: The endometriotic implant area of the group treated with green tea extract was significantly lower (p=0,022) RR=0,455, 95%CI=0.065-0,96) compared to the control group. The serum level of SOD in EG and CG were 5.33±0.52 ng/ml and 5.20±0.91 ng/ml, respectively (p=0.507). Conclusion: Green tea extract inhibits endometriotic implant progression and increases the level of serum SOD in endometriosis-induced rat models.

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.

NF-ĸB expression in endometriosis induced rat uterine tissue

Objective: Our aim in this study is to examine the effects of endometriosis on uterine tissue.&#x0D; Materials and methods: Two groups were formed, with eight rats in each group. Sham group was subjected only saline solution for 7 days. The endometriosis (EM) model was induced with estradiol benzoate (EB). In the EM group, EB was given to rats for 7 days. At the end of the experiment, blood was taken from the animals and serum total antioxidant status (TAS) and total oxidant status (TOS) values were studied. Uterine tissues were fixed in formalin and embedded in paraffin blocks. NF-ĸB 3 immune staining were performed on uterine sections. The results were examined under the microscope.&#x0D; Results: Compared to sham group, TAS values were significantly decreased and TOS values were significantly increased in serum of rats belonging to EM group. In the analysis of NF-ĸB expression in uterine tissue of sham group, the expression was slight and found only in connective tissue cells and inflammatory cells. NF-ĸB expression was mainly negative. After EM induction, NF-ĸB expression was increased in degenerated epithelial cells and gland cells, inflammatory cells around the glands and blood vessel endothelial cells and lamina propria.&#x0D; Conclusion: We think that NF-κB signal may be a determinant in the treatment of endometriosis.&#x0D; Keywords: endometriosis, immunohistochemistry, NF-κB, biochemistry, rat

Ameliorative effects of apigenin on a rat model of endometriosis

Objectives: Apigenin and parthenolide as natural products have potent antioxidant and anti-inflammatory outcomes that could make them a perfect option for endometriosis therapy. This study aimed to determine the effects of apigenin and parthenolide on created endometrial implants in a rat model of endometriosis. Methods: Thirty-nine mature, female Sprague-Dawley rats were assigned randomly to six experimental groups four weeks after endometriosis induction. Group 1 (n = 5): Control (CTRL) that opened and closed the abdomen; Group 2 (n = 6): Peritoneal and ovarian endometriosis (POE) + drug-free; Group 3 (n = 7): POE+ Apigenin (APG) (50 mg/kg); Group 4 (n = 7): POE+ Parthenolide (PTL) (10 mg/kg); Group 5 (n = 7): POE+ Apigenin (APG) (50 mg/kg) + Parthenolide (PTL) (10 mg/kg); Group 6 (n = 7): POE+ DMSO. An endometriosis model was created, and histopathological analysis and biochemical evaluation were performed. Serum and peritoneal levels of pro-and-anti-inflammatory cytokine, and oxidative stress of implant tissue were measured. Results: Serum IL-37 levels decreased significantly in the APG-treated group compared to the drug-free group (p = 0.016). The peritoneum and ovary endometriosis histopathologic scores were significantly lower in APG-treated (p = 0.001) and PTL-treated (p = 0.001) groups in comparison to the drug-free group. The oxidative stress index (OSI) values were increased statistically significantly in ovary endometriosis tissue in the drug-free group, (p = 0.001). However, compared to the drug-free group, OSI values decreased statistically significantly in the APG-treated group (p = 0.003). Conclusions: The application of apigenin caused a decrease in oxidative stress and an improvement in histopathological grade. Apigenin may be a novel therapeutic agent for the treatment of endometriosis.

High intensity interval training is superior to moderate intensity continuous training in enhancing the anti-inflammatory and apoptotic effect of pentoxifylline in the rat model of endometriosis

High intensity interval training is superior to moderate intensity continuous training in enhancing the anti-inflammatory and apoptotic effect of pentoxifylline in the rat model of endometriosis

Complex Interplay between Autophagy and Oxidative Stress in the Development of Endometriosis.

Endometriosis (Endo) is a chronic gynecological disease. This paper aimed to evaluate the modulation of autophagy, oxidative stress and apoptosis with Açai Berries in a rat model of endometriosis. Endometriosis was induced with an intraperitoneal injection of minced uterus tissue from a donor rat into a recipient one. The abdominal high-frequency ultrasound (hfUS) analysis was performed at 7 and 14 days from the endometriosis induction to evaluate the growth of the lesion during the experiment. Seven days from the induction, once the lesions were implanted, an Açai Berry was administered daily by gavage for the next seven days. At the end of the experiment, the hfUS analysis showed a reduced lesion diameter in animals given the Açai Berry. A macroscopical and histological analysis confirmed this result. From the molecular point of view, Western blot analyses were conducted to evaluate the autophagy induction. Samples collected from the Endo group showed impaired autophagy, while the Açai Berry administration inhibited PI3K and AKT and ERK1/2 phosphorylation and promoted autophagy by inactivating mTOR. Additionally, Açai Berry administration dephosphorylated ATG1, promoting the activity of the ATG1/ULK1 complex that recruited Ambra1/Beclin1 and Atg9 to promote autophagosome nucleation and LC3II expression. Açai Berry administration also restored mitophagy, which increased Parkin cytosolic expression. The Açai Berry increased the expression of NRF2 in the nucleus and the expression of its downstream antioxidant proteins as NQO-1 and HO-1, thereby restoring the oxidative imbalance. It also restored the impaired apoptotic pathway by reducing BCL-2 and increasing BAX expression. This result was also confirmed by the TUNEL assay. Overall, our results displayed that Açai Berry administration was able to modulate autophagy, oxidative stress and apoptosis during endometriosis.

Induction of Experimental Endometriosis in Rat: Evaluation of Systemic Inflammatory Response and Liver Tissue Changes

Introduction: Nowadays non-alcoholic fatty liver disease (NAFAD) is considered as a serious problem in human societies. Recently, the possibility of an association between endometriosis and NAFAD has been considered. This study was designed to evaluate some general inflammation parameters and hepatic lesions during and after experimental endometriosis. Material and Methods: In 20 female rats, the endometriosis model was induced by suturing parts of the uterine horn wall to the mesenteric gut. After four weeks, the rats in group I were euthanized and endometriosis cysts and some fragments of their liver were used for histopathological evaluation. At the same time, endometrial cysts were surgically removed in the rats of group II and they were kept for four weeks later. In addition, hematobiochemical evaluation was performed. In group II, similar evaluative investigations were performed 8 weeks after experimental surgery. Results: Significant increase in triglyceride, LDL, AST, ALP, ALT and estrogen parameters was observed in this study (P˂0.05), Whereas, total WBC count, lymphocyte, PCV and HDL level decreased significantly (P˂0.05). In histopathological evaluation, induction of endometriosis was confirmed at the microscopic level, but no evidence of fatty liver or hepatic inflammation was found. Conclusion: Despite notable changes in some hematobiochemical factors in rats with experimental endometriosis, there was no evidence of fatty liver and hepatic inflammation. Therefore, there may be no association between endometriosis and non-alcoholic fatty liver disease.

Ornidazole Reduces the Progression of Endometriosis in a Rat Model

Objective: The aim of this study was to investigate the effectiveness of ornidazole in inhibiting the progression of endometriosis in a rat model. Design: This was an in vivo experiment, including the ornidazole group (n = 16) and a control group (n = 14). Rats were provided with free access to water containing ornidazole (1 g/L) or drinking water only for 14 days. Materials and Methods: Surgical induction of endometriosis was performed in Sprague Dawley rats via autologous endometrial transplantation. Rats were provided with free access to water containing ornidazole (1 g/L) or drinking water only for 14 days. Once the rats were euthanized (ornidazole group, n = 16; control group, n = 14), histological signatures and the volumes of endometriosis lesions were assessed. Cells positive for the inflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were counted. Angiogenesis was identified by assessing vascular endothelial growth factor (VEGF) and microvessel density. Results: The median lesion volume was lower in the ornidazole group (20.2 mm³; range, 5.7–53.3 mm³) than in the control group (81.3 mm³; range, 32.8–122.2 mm³; p = 0.007). Median IL-1β cell counts were 5.3 (range, 4.5–6.4) for ornidazole and 11.7 (range, 9.4–15.4) for control (p < 0.001). Mean IL-6 cell counts were 5.6 ± 1.8 for ornidazole and 11.3 ± 4.1 for control (p < 0.001). Median TNF-α cell counts were 5.7 (range, 4.5–7.2) for ornidazole and 12.1 (range, 10.0–15.9) for control (p < 0.001). Median VEGF cell counts were 8.1 (range, 6.5–11.4) for ornidazole and 18.3 (range, 14.2–21.0) for control (p = 0.001). Median microvessel density values were 11.3/HPF (range, 7.7–21.8) for ornidazole and 28.7/HPF (range, 13.1–48.2) for control (p = 0.012). Limitations: This study is a short period and small sample size experiment. In this study, multiple drug concentrations were not used. We did not use in vitro models to assess the anti-inflammatory and antiangiogenic effects of ornidazole on endometriosis, and the specific anti-inflammatory and antiangiogenic mechanisms associated with ornidazole need to be further investigated. Conclusion: Ornidazole restricts the growth of endometriosis in rats, possibly by exerting anti-inflammatory and antiangiogenic effects.

Angiogenic and Inflammatory Alterations of Endometriotic Lesions in a Transgenic Animal Experimental Model With Loss of Expression of PPAR-Alpha Receptors

Peroxisome proliferator-activated receptors (PPARs) have been proposed as a medical treatment against endometriosis in preclinical and clinical studies. Their effect seems to be triggered through the suppression of angiogenesis. In the present study, we used a transgenic animal model with a loss of expression of PPAR-alpha receptors to examine their effect on the course of surgically induced endometriotic lesions. Ten C57BL/6 mice that served as controls and 10 B6;129S4-PPARatm1Gonz/J t transgenic mice characterized by absolute loss of expression of PPAR-alpha receptors were used for induction of endometriosis with a previously described surgical technique. Five animals (50%) exhibited abundant endometriotic crypts in the control group whereas only one (10%) animal in the transgenic experimental group had a similar pathological image. Neo-vascularization significantly differed among the two groups (p=0.034) favoring the control group as it was extremely limited in half of the PPAR-alpha null animals. The median inflammation score was 2.5 (1-4) in the P B6;129S4-PPARatm1Gonz/J group, whereas it was minimal, 1 (0-2), in the C57BL/6 group. However, these differences were not statistically significant (p=0.101). The fibroblastic activity was also very limited in the PPAR-alpha-deficient model, whereas animals belonging to the control group exhibited an intermediate increase of this index (p=0.022). Surgically induced endometriotic implants in animals with loss of expression of PPAR-alpha receptors exhibit significant differences in their pathology compared to lesions induced in control animals. This information suggests that PPAR-alpha receptors have a significant impact on the course of the disease, indicating that they may serve as potential targets for future medical therapies.

Ectopic endometriosis in the pelvic cavity evokes bladder hypersensitivity via transient receptor potential ankyrin 1 hyperexpression in rats.

In women with chronic pelvic pain (CPP), interstitial cystitis/bladder pain syndrome (IC/BPS) and endometriosis frequently coexist. The mechanism of these diseases coexisting is explained by cross-sensitization between endometriosis and IC/BPS. The overlapped symptoms may be related to cross-sensitization with transient receptor potential vanilloid 1 (TRPV1) and/or transient receptor potential ankyrin 1 (TRPA1) hyperexpression. This study was aimed at exploring whether bladder hypersensitivity is evoked in the surgically induced ectopic endometriosis rat and whether TRPV1 and/or TRPA1 play a vital role. A total of 63 Sprague-Dawley female rats were divided into two groups, 39 for physiological examination and 24 for molecular analysis. Surgical induction of ectopic endometriosis (ENDO, n=27), surgical sham treatment (n=18), and treatment for endometriosis by GnRH analog (ENDO-G) (n=18) were performed. Bladder function was investigated by cystometry (for TRPV1 in the sham [n=6] and ENDO [n=9] groups and for TRPA1 in the sham [n=6], ENDO [n=9], and ENDO+G [n=9] groups), and TRPV1 and TRPA1 mRNA expressions were measured using real-time qPCR in the bladder and dorsal root ganglia (DRGs). On cystometry, the relative intercontraction interval (ICI) after/before resiniferatoxin (RTx; TRPV1 activator) infusion to the bladder showed no significant difference between the two groups, whereas relative ICI after/before allyl isothiocyanate (AITC; TRPA1 activator) infusion was significantly lower in the ENDO group than in the sham group. TRPA1 mRNA expression in the bladder and L5 DRG was considerably higher in the ENDO group than in the sham group on real-time qPCR. TRPA1 mRNA hyperexpression and bladder hypersensitivity after AITC infusion were reduced in the ENDO-G group. Bladder cross-sensitization in ENDO rats occurs in association with hyperexpression of TRPA1 at both the DRG and the bladder mucosa. This can be understood by the "cross-sensitization of endometriosis to bladder" theory explaining overlapping symptoms among BPS/IC and ectopic endometriosis.

Importance and Surgical Methods of Induction of Endometriosis and Osteoporosis Following Menopause in Rats: an Overview Study

Introduction: Endometriosis is one of the main causes of pelvic pain and subfertility, which is characterized by endometrial-like tissues outside the uterus and primarily is created in the pelvic peritoneum, ovaries, walls between the rectum and vagina and in rare cases in the diaphragm, pleura and pericardium. Some risk factors for endometriosis are obstruction in menstrual hemorrhage, an increase in the duration of endogenous estrogen, short menstrual cycles and childbirth at an early age. On the other hand, osteoporosis is a metabolic disease that is determined by bone mineral density and the destruction of the bone microstructure that increases the risk of bone fracture. About 200 million people worldwide are suffering from osteoporosis, that 34% of them are women over 50 years old. The first and most commonly used model for the induction of this disease is the ovariectomy model in rats, which gives a model of the relationship between osteoporosis and menopause. Conclusion: Endometriosis animal models are highly contributing to the development of new non-invasive diagnostic tools and improve therapeutic methods for treatment of endometriosis in women. Although no animal models are absolutely ideal and excellent, but the presence of many similarities in the response of the human skeletal system and rats to reduce estrogen levels and therapeutic compounds caused by the ovariectomy model of the rat, a suitable model for osteoporosis research. The response of rat bones to ovariectomy depends on the type of bone (trabecular against cortical), bone sites (femur, proximal Tibia, and lumbar vertebrae) and it depends on the time elapsed after ovariectomy (the time required to reduce the amount of estrogen levels).

The effect of hyperbaric oxygen therapy in the inflammatory response in a mouse model of endometriosis: An experimental study.

BackgroundEndometriosis pathogenesis is related to the inflammation shown by the secretion of pro-inflammatory mediators. This hypoxia condition can stimulate this condition.ObjectiveTo investigate the effect of hyperbaric oxygen therapy (HBOT) on the inflammation reaction of endometriosis-induced mice.Materials and MethodsThe animals were designated into 3 groups: I) the pre-test group, II) the post-test group receiving the HBOT, and III) the post-test group without HBOT. All groups were subjected to induction of endometriosis by xenotransplantation for 15 days. HBOT was given 30 min 3 times a day for 10 days. The evaluation of the HBOT effect was conducted by examining the endometrial tissue. The inflammation level was evaluated using the Klopfleisch semiquantitative scoring system (index remmele scale), whilst the expression of nuclear factor kappa (NFB) beta was measured by immunohistochemical staining.ResultsThe results showed that group I demonstrated the highest level of inflammation degree (9.41 1.99) compared to the post-test groups (group II: 1.60 0.53; group III: 2.42 0.53). The HBOT-groups was found to have the lowest inflammation level compared to the non-HBOT group (p = 0.020). The results demonstrated that HBOT lowered the peritoneal inflammation degree caused by the endometrial lesion in mice. NFB expression on the post-test groups was significantly decreased, compared to the pre-test group (p 0.001), with a strong correlation between the NFB expression and the peritoneal inflammation level (p 0.001, r = 0.670).Conclusion HBOT significantly reduced the inflammation level on the endometrial lesion in mice, involving the NFB pathway.

Evaluation of the potential role of diethylstilbestrol on the induction of endometriosis in a rat model – An alternative approach

Evaluation of the potential role of diethylstilbestrol on the induction of endometriosis in a rat model – An alternative approach

A Mouse Model of Endometriosis with Nanoparticle Labeling for In Vivo Photoacoustic Imaging.

Endometriosis is a condition of the female reproductive tract characterized by endometrium-like tissue growing outside the uterus. Though it is a common cause of pelvic pain and infertility, there is currently no reliable noninvasive method to diagnose the presence of endometriosis without surgery, and the pathophysiological mechanisms that lead to the occurrence of symptoms require further inquiry. Due to patient heterogeneity and delayed diagnosis, animal models are commonly used to study the development of endometriosis, but these are costly due to the large number of animals needed to test various treatments and experimental conditions at multiple endpoints. Here, we describe a method for synthesis of multimodal imaging gold-fluorescein isothiocyanate (FITC) nanoparticles with preclinical application via induction of nanoparticle-labeled endometriosis-like lesions in mice. Labeling donor endometrial tissue fragments with gold-FITC nanoparticles prior to induction of endometriosis in recipients enables in vivo detection of the gold-labeled lesions with photoacoustic imaging. The same imaging method can be used to visualize embryos noninvasively in pregnant mice. Furthermore, the conjugated FITC dye on the gold nanoparticles allows easy isolation of labeled lesion tissue under a fluorescence dissection microscope. After dissection, the presence of gold-FITC nanoparticles and endometrium-like histology of lesions can be verified through fluorescence imaging, gold enhancement, and immunostaining. This method for in vivo imaging of endometriosis-like lesions and fluorescence-guided dissection will permit new experimental possibilities for the longitudinal study of endometriosis development and progression as well as endometriosis-related infertility.

397 Application of cabergoline and celecoxib at experimental endometriosis

397 Application of cabergoline and celecoxib at experimental endometriosis

Effects of endometriosis on immunity and mucosal microbial community dynamics in female olive baboons

Endometriosis is defined as the growth of endometrial tissue in ectopic locations, and is associated with altered immune and microbial phenotypes. It is unclear if these changes are the result of the disease or may be causative. We induced endometriosis in non-human primates (Papio Anubis) to test our hypothesis that the growth of endometriotic lesions results in alterations in immune and microbial dynamics that may advance disease progression. Baboon samples were collected pre-inoculation (prior to disease induction), at 3, 6, 9, and 15 months after disease induction. Tolerant regulatory T-cells (Tregs) and inflammatory T-helper 17 (Th17) cells were identified in peripheral blood and within the eutopic/ectopic endometrial tissues. Microbiome communities were identified in fecal/urine samples. The induction of endometriosis decreased peripheral Tregs cells while Th17 cells increased at all post-induction collections, thus reducing the Tregs:Th17 cells ratio, indicating systemic inflammation. Microbiome diversity and abundance were altered at each sample site after disease induction. Thus, induction of endometriosis in baboons caused an immune shift toward an inflammatory profile and altered mucosal microbial profiles, which may drive inflammation through production of inflammatory mediators. Immune and microbial profiling may lead to innovative diagnostic tools and novel therapies for endometriosis treatment.