Size Of Endometriotic Implants Research Articles

A Computational Exploration: Docking Analysis of Compounds from Foeniculum vulgare as Potential Aromatase Inhibitors for Endometriosis Candidate Therapy

Aromatase inhibitors (AI) have controlling symptoms and size of endometriotic implants, making them a promising second-line therapy for endometriosis treatment.pretreatment with letrozole, an AI, combined with leuprolide acetate and resveratrol has been found to improve in vitro fertilization (IVF) outcomes in women mild endometriosis.in this study we screening and analysis of ten phenolic compounds from Foeniculum vulgare using molecular docking with Mcole server.from this results showed that three phenolic trans resveratrol (TR), caempherol coumaril (CC) have low gibbs energy compare with resveratrol (R). The binding modalities of compound TR and compound R were hydrogen-bonding between the hydroxyl and oxygen atom and Thr310 and hydrophobic interactions with Phe187, Ala272, Asp275, Ala189.and compound R exhibited cation-π interactions between Val336 as binding activity from aromatase.aromatase inhibitors and resveratrolfrom fennel lies in the potential of resveratrol to modulate hormonal pathways, including aromatase inhibition.

Increased circulating cell-derived microparticle levels in deep infiltrating endometriosis patients with larger implants

Objective: Circulating cell-derived microparticles have been reported to be elevated in inflammatory and procoagulant conditions including deep infiltrating endometriosis. The objective of this pilot study was to investigate whether higher circulating cell-derived microparticle levels may be associated with specific clinical features and the extension or severity of deep infiltrating endometriosis. Methods: This is an observational analytical cross-sectional study, including three groups of patients undergoing gynecological surgery. The DIE group included 75 patients with deep infiltrating endometriosis, the control group (C group) consisted of 39 patients without endometriosis, and a positive control group was composed of 31 patients with ovarian endometriomas but not deep infiltrating endometriosis (OE group). Venous blood samples for circulating cell-derived microparticle determinations in plasma were obtained before surgery. The following variables were assessed: severe dysmenorrhea, dyspareunia, non-cyclic chronic pelvic pain, dyschezia, dysuria, hematuria, rectal bleeding, sterility, presence of ovarian endometrioma, adenomyosis, and adhesions, rASRM (revised American Society for Reproductive Medicine) stage, Enzian classification, number of sites affected, and the cumulative size of deep infiltrating endometrial implants. Results: Circulating cell-derived microparticle levels were statistically higher in the DIE group compared with the C group ( p-value = 0.001). None of the variables analyzed showed higher levels of circulating cell-derived microparticles in the DIE group, except for a significant positive correlation between the cumulative size of deep infiltrating endometrial lesions and circulating cell-derived microparticle levels ( r = 0.264, p = 0.022). Conclusion: Patients having deep infiltrating endometriosis with a larger cumulative size of endometriotic implants showed higher circulating cell-derived microparticle levels suggesting an increased inflammatory and/or hypercoagulable systemic status in this more severe form of the disease. Further research is needed to assess our findings and to explore the role of circulating cell-derived microparticles in the pathophysiology of deep infiltrating endometriosis.

Noninvasive Monitoring of Lesion Size in a Heterologous Mouse Model of Endometriosis.

Here, we describe a protocol for the implementation of a heterologous mouse model in which progression of endometriosis can be assessed in real time through noninvasive monitoring of fluorescence emitted by implanted ectopic human endometrial tissue. For this purpose, biopsies of human endometrium are obtained from donor women ongoing oocyte donation. Human endometrial fragments are cultured in the presence of adenoviruses engineered to express cDNA for the reporter fluorescent protein mCherry. Upon visualization, labeled tissues with an optimal rate of fluorescence after infection are subsequently chosen for the implantation in recipient mice. One week prior to the implantation surgery, recipient mice are oophorectomized, and estradiol pellets are placed subcutaneously to sustain the survival and growth of lesions. On the day of surgery mice are anesthetized, and peritoneal cavity accessed through a small (1.5 cm) incision by the linea-alba. Fluorescently labeled implants are tweezed, briefly soaked in glue and attached to the peritoneal layer. Incisions are sutured, and animals left to recover for a couple of days. Fluorescence emitted by endometriotic implants is usually non-invasively monitored every 3 days for 4 weeks with an in vivo imaging system. Variations in the size of endometriotic implants can be estimated in real time by quantification of the mCherry signal and normalization against the initial time-point showing maximal fluorescence intensity. Traditional preclinical rodents of models of endometriosis do not allow non-invasive monitoring of lesion in real time but rather allow evaluation of the effects of drugs assayed at the end point. This protocol allows one to track lesions in real time and is more useful to explore the therapeutic potential of drugs in preclinical models of endometriosis. The main limitation of the model thus generated is that non-invasive monitoring is not possible over long periods of time due to the episomal expression of Ad-virus.

Clarithromycin regresses endometriotic implants in rat endometriosis model

The aim of this study was to investigate the effect of clarithromycin in rat endometriosis and its association with matrix metalloproteinase-9 (MMP-9) expression. After surgical induction of endometriosis, 27 rats were randomised into three groups. Size of endometriotic implants were evalutated and rats in group I (n = 9) were given 100 mg/kg/day of oral clarithromycin, rats in group II (n = 9) were given single 1 mg/kg s.c. injection of leuprolide acetate and rats in group III (n = 9) were not given any medication for 21 days. At the end of 21 days of medication, remaining 23 rats were sacrificed to evaluate morphological and histological features of implants. There was a significant difference between the groups in implant volumes (p = 0.004) before and after medication. Regression of implants were significantly higher in groups I and II than that in control group (p = 0.009 and p = 0.011, respectively). After medication, in group I the implant volume decreased from 62 (12–166) mm3 to 26 (3–87) mm3 (p = 0.012) and in group II the volume decreased from 224 (76–1135) mm3 to 62 (26–101) mm3 (p = 0.028). There was a significant difference between groups in histopathological score (p = 0.024). The epithelial immunohistochemical score of MMP-9 was significantly lower in group II than that in control group (p = 0.014). In conclusion, clarithromycin regresses endometriotic implants in rats, but not via MMP-9.

Effects of Simvastatin on Retinoic Acid System in Primary Human Endometrial Stromal Cells and in a Chimeric Model of Human Endometriosis

Retinoic acid (RA) may promote survival or apoptosis of cells, depending on the levels of binding proteins: apoptosis-inducing cellular RA binding protein 2 (CRABP2), and cell survival-promoting fatty acid binding protein 5 (FABP5). Increased cellular uptake of retinol and altered actions of RA related to reduced expression of CRABP2 may contribute to the development of endometriosis. Recently statins have been shown to inhibit growth of human endometrial stromal (HES) cells and to reduce the number and size of endometriotic implants in experimental models of this disorder. The objective of the study was to determine whether effects of simvastatin on HES cells and experimental endometriotic implants are related to the modulation of the RA system. Effects of simvastatin and RA on proliferation and apoptosis of HES cells were evaluated. Expression of stimulated by RA 6 (STRA6), CRABP2, and FABP5 was determined by real-time PCR and Western blotting. Effects of simvastatin were also evaluated in a nude mouse model of human endometriosis. Simvastatin potentiated an inhibitory effect of RA on growth of HES cells. In HES cells, simvastatin induced expression of STRA6 and CRABP2 but not FABP5. Similarly, simvastatin treatment of nude mice bearing human endometrial xenografts led to an increased expression of CRABP2 and STRA6 proteins in ectopic lesions. Simvastatin interacts with the RA system, inducing the expression of the key protein regulating the uptake of retinol (STRA6) and the expression of apoptosis-promoting CRABP2. These effects may contribute to cooperative apoptosis-inducing effects of simvastatin and RA and support the examination of these compounds in the treatment of endometriosis.

Resveratrol Inhibits Development of Experimental Endometriosis In Vivo and Reduces Endometrial Stromal Cell Invasiveness In Vitro1

Endometriosis is a common gynecologic disorder characterized by ectopic attachment and growth of endometrial tissues. Resveratrol is a natural polyphenol with antiproliferative and anti-inflammatory properties. Our objective was to study the effects of resveratrol on human endometriotic implants in a nude mouse model and to examine its impact on human endometrial stromal (HES) cell invasiveness in vitro. Human endometrial tissues were obtained from healthy donors. Endometriosis was established in oophorectomized nude mice by intraperitoneal injection of endometrial tissues. Mice were treated with 17β-estradiol (8 mg, silastic capsule implants) alone (n = 16) or with resveratrol (6 mg/mouse; n = 20) for 10-12 and 18-20 days beginning 1 day after tissue injection. Mice were killed and endometrial implants were evaluated. A Matrigel invasion assay was used to examine the effects of resveratrol on HES cells. We assessed number and size of endometriotic implants in vivo and Matrigel invasion in vitro. Resveratrol decreased the number of endometrial implants per mouse by 60% (P < 0.001) and the total volume of lesions per mouse by 80% (P < 0.001). Resveratrol (10-30 μM) also induced a concentration-dependent reduction of invasiveness of HES by up to 78% (P < 0.0001). Resveratrol inhibits development of endometriosis in the nude mouse and reduces invasiveness of HES cells. These observations may aid in the development of novel treatments of endometriosis.

Simvastatin Protects against the Development of Endometriosis in a Nude Mouse Model

Endometriosis is a common condition associated with infertility and pelvic pain in women. Recent in vitro studies have shown that statins decrease proliferation of endometrial stroma (ES) and inhibit angiogenesis. The aim was to evaluate effects of simvastatin on development of endometriosis in a nude mouse model. Proliferative phase human endometrial biopsies were obtained from healthy donors and established as organ cultures or used to isolate ES cells. To establish endometriosis in the nude mouse, endometrial tissues were maintained in 1 nm estradiol (E) for 24 h and subsequently injected into ovariectomized nude mice. Mice (n = 37) were treated with E (8 mg, SILASTIC capsule implants; made in author laboratory) alone or with E plus simvastatin (5 or 25 mg/kg x d) for 10 d beginning 1 d after tissue injection (from three donors). Mice were killed and examined for disease. Effects of simvastatin on matrix metalloproteinase-3 (MMP-3) were evaluated in cultures of ES cells. The number and size of endometriotic implants were measured. Simvastatin induced a dose-dependent decrease of the number and size of endometrial implants in mice. At the highest dose of simvastatin, the number of endometrial implants decreased by 87%, and the volume by 98%. Simvastatin also induced a concentration-dependent decrease in MMP-3 in the absence and presence of inflammatory challenge (using IL-1alpha). Simvastatin exerted a potent inhibitory effect on the development of endometriosis in the nude mouse. Mechanisms of action of simvastatin may include inhibition of MMP-3. The present findings may lead to the development of novel treatments of endometriosis involving statins.