Implantation Of Endometrial Tissue Research Articles

#111 : MMP-9 to TIMP-1 Expression Ratio on Endometrioma Favors Tissue Invasion: A Study on Chicken Chorioallantoic Membrane (CAM)

Background and Aims: Endometrioma occurs through the implantation of endometrial tissue in the ovary. The establishment of endometriotic lesions requires endometrial cells to invade the ovary by remodelling the extracellular matrix (ECM). It is plausible that these cells express protease. MMP-9 is a significant protease controlled by its natural inhibitor, TIMP-1. The balance between MMP-9 and TMIP-1 plays a critical role in the invasion of endometrioma that has never been investigated before. This study aimed to examine the correlation between MMP-9/TIMP-1 expression ratio and MMP-9 activity with the invasion of endometrioma tissue. Method: This study was conducted on 35 samples of endometrioma tissue obtained from 27 women with endometriosis at Dr Sardjito General Hospital, Yogjakarta. The tissue was then implanted into CAM to examine its invasion capability. Invasion scores were assessed using hematoxylin-eosin staining. MMP-9/TIMP-1 expressions ratio was analysed using western blot, while MMP-9 activity in degrading ECM components was determined using gelatin zymography. The Spearman correlation assesses the correlation between variables with significance set as p[Formula: see text]0.05. Results: The results showed a positive linear correlation between the MMP-9/TIMP-1 expression ratio and invasion scores of endometrioma tissue (r=0.486; p=0.003). In addition, the Kruskal-Wallis test showed there was a significant difference between the MMP-9/TIMP-1 expression ratio in each invasion score of endometrioma (p=0.032), and further analysis by Mann-Whitney post hoc tests revealed that significant differences were between invasion score 1 and 3 (p=0.037), also between invasion score 1 and 4 (p=0.010). MMP-9 activity had a strong positive linear correlation with invasion scores of endometrioma tissue (r=0.646; p=0.000). Conclusion: MMP-9 activity in degrading extracellular matrix promotes the invasion of endometrioma. The imbalance between MMP-9 and TIMP-1 enhances the capacity of endometrioma to break down ECM. Higher MMP-9 expression over TIMP-1 expression gives rise to the invasion of endometrioma.

Parthenolide repressed endometriosis induced surgically in rats: Role of PTEN/PI3Kinase/AKT/GSK-3β/β-catenin signaling in inhibition of epithelial mesenchymal transition

AimPI3K/AKT/GSK-3β/β-catenin signaling pathway is a triggering factor for epithelial to mesenchymal transition (EMT) which plays a pivotal role in the pathogenesis of endometriosis. Parthenolide is a sesquiterpene lactone extract that has anti-inflammatory, analgesic and anticancer properties. Hence, we investigated the effect of parthenolide against EMT in the endometrial tissue implants and immortalized epithelial endometriotic cell lines 12Z. Main methodsTwenty- four female Rats with surgically induced endometriosis were treated with parthenolide (2, 4 mg/kg), for 4 weeks. Endometriotic cell line 12Z was used to identify the effect of parthenolide on the wound healing, cellular migration and invasion properties of endometriotic cells. Key findingsParthenolide decreased the endometriotic implant tissue expression of total PI3K, PI3K-p85, p-AKT, p/total AKT, p-GSK-3β, P/total GSK-3β, and nβ-catenin, as well as increased E-cadherin and decreased vimentin mRNA expression. Parthenolide upregulated PTEN immunoreactivity as well as the endometriotic tissue caspase-3, caspase-9, BAX levels while reducing Bcl2 level. Additionally, parthenolide decreased endometriotic tissue implants surface area and histopathological score of the epithelial growth. SignificanceOur findings showed that parthenolide in a dose dependent manner inhibited PI3K/AKT/GSK-3β/nβ-catenin cascade via enhancement of PTEN with subsequent inhibition of EMT evidenced by elevation of the epithelial marker, E-cadherin and reduction of mesenchymal marker, vimentin, of the endometriotic implants in addition to reversal of invasion and migration properties of epithelial endometriotic cell lines. These findings provide a valuable therapeutic approach for treatment of endometriosis.

Peritoneal immune microenvironment of endometriosis: Role and therapeutic perspectives.

Endometriosis, an estrogen-dependent chronic inflammatory disease characterized by the growth of endometrium-like tissues outside the uterine cavity, affects 10% of reproductive-age women. Although the pathogenesis of endometriosis is uncertain, it is widely accepted that retrograde menstruation results in ectopic endometrial tissue implantation. Given that not all women with retrograde menstruation develop endometriosis, immune factors have been hypothesized to affect the pathogenesis of endometriosis. In this review, we demonstrate that the peritoneal immune microenvironment, including innate immunity and adaptive immunity, plays a central role in the pathogenesis of endometriosis. Current evidence supports the fact that immune cells, such as macrophages, natural killer (NK) cells, dendritic cells (DCs), neutrophils, T cells, and B cells, as well as cytokines and inflammatory mediators, contribute to the vascularization and fibrogenesis of endometriotic lesions, accelerating the implantation and development of ectopic endometrial lesions. Endocrine system dysfunction influences the immune microenvironment through overexpressed estrogen and progesterone resistance. In light of the limitations of hormonal therapy, we describe the prospects for potential diagnostic biomarkers and nonhormonal therapy based on the regulation of the immune microenvironment. Further studies are warranted to explore the available diagnostic biomarkers and immunological therapeutic strategies for endometriosis.

Down-Regulation of miR-93 Negatively Correlates with Overexpression of VEGFA and MMP3 in Endometriosis: A Cross-Sectional Study.

Endometriosis is identified as presence of the endometrium outside the uterine cavity. Retrograde menstruation contributes to the endometrial tissue implantation and the establishment of endometriotic lesions at ectopic sites. It has been suggested that the endometriotic lesions are rich in angiogenic growth factors, while they have an essential role in survival and invasion of these cells. We investigated regulation of microRNA-93 (miR-93) and its involvement with vascular endothelial growth factor A (VEGFA) and matrix metalloproteinase (MMP) 3 expression in women with endometriosis. This was a cross-sectional study at Central Surgical Installation, Dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia, between October 2020 and November 2021. Eutopic and ectopic endometrial tissues were collected from 30 subjects with laparoscopically-confirmed endometriotic women. Normal endometrial cells of non-endometriosis women served as controls. Total RNA was isolated from all samples and a quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to analyze the expression of miR-93, VEGFA and MMP. There was no significant difference in the expression levels of VEGFA (2.14 ± 0.50, P=0.719) and MMP3 (2.99 ± 0.42, P=0.583) between endometriotic lesions of endometriosis women and the healthy endometrium. Expression of miR-93 was significantly lower in the eutopic endometrium (16.7 fold) and ectopic endometriotic lesion (20 fold) compared to the normal endometrium (P<0.001). Furthermore, we also observed a significant correlation between miR-93, VEGFA expression in eutopic endometrium obtained from women with endometriosis (r=-0.544, P=0.029). Expression of the miR-93 was also negatively correlated with MMP3 expression in both eutopic (r=-0.412, P=0.01) and ectopic (r=-0.539, P=0.03) endometrial cells of women with endometriosis. VEGFA and MMP3 expression levels trended to be increased in both eutopic and ectopic endometrial tissues of endometriosis women, while down-regulation of miR-93 might be involved in the alteration of VEGFA and MMP3 in endometriosis.

Endometriosis externa: A rare presentation

Endometriosis externa is presence of endometrial glands and stroma outside uterus. Umbilical endometriosis (also called Villar’s nodules) and subcutaneous endometriosis are rare conditions that occur in elderly women without any menstrual complaints and pelvic endometriosis. The overall incidence of umbilical endometriosis is very low (0.1-0.5%). Here we report a rare case of endometriosis externa with umbilical menstruation in a woman with a previous history of cesarean section and myomectomy. After complete evaluation, the patient underwent excision of the endometriotic lesion with abdominoplasty with mesh repair. The possible cause of this type of endometriosis can be secondary type due to direct implantation of endometrial tissue in the subcutaneous tissue during the previous surgeries.

The Intussusception of Appendix Due to Extrapelvic Endometriosis: A Case Report

Endometriosis is among the most frequent causes of appendiceal intussusception. However, there are limited data about this condition. Still, clinical manifestations, diagnosis, and treatment are the same in almost all cases due to accidental implantation of endometrial tissue inside the appendiceal wall. Finally, the only choice of treatment is appendectomy.&#x0D; Here we describe a middle-aged woman with vague pelvic pain that underwent a laparoscopic cystectomy, and during surgery, we came across a mass-like appendix. The pathology report declared that some endometrial tissue inside the appendix confirms the diagnosis of appendiceal intussusception due to endometriosis.

Episiotomy Scar Endometriosis: A Case Report and Review of Literature.

Abstract&#x0D; Background&#x0D; Endometriosis is defined as the presence and growth of endometrial tissue implants, outside the uterine cavity. It may be pelvic and extra-pelvic sites. Endometriosis in an episiotomy scar is extremely rare but can lead to significant morbidity in patients due to local infiltration. This condition usually presents with clinical triad of history of episiotomy, tender nodule at the scar site and cyclical pain.&#x0D; Case Presentation&#x0D; Here we report one such case of episiotomy scar endometriosis in the perineum of a 30 years young female (P1L1) which presented with swelling and pain in perineal region. The clinical examination and Ultrasonography (USG) corroborate with diagnosis of episiotomy scar endometriosis. Excision was done and histopathological examination confirmed the diagnosis.&#x0D; Conclusion&#x0D; Episiotomy scar endometriosis should always be kept in differential diagnosis when a lady presents with painful perineal swelling which increases during menstruation. This can be diagnosed with clinical and radiological examination. Wide local excision is the treatment of choice. Confirmation of the lesion can be done with histopathological examination.&#x0D; Keywords: Episiotomy scar endometriosis, perineal scar endometriosis, scar endometriosis&#x0D;

Gynaecologic History During Adolescence to Predict Endometriosis Earlier

Background. Endometriosis is a chronic gynecological disorder that generally affects women of reproductive age which is characterized by implantation of endometrial tissue, both glands and stroma outside the uterus. Research shows that the initial onset of endometriosis patients begins in adolescence. The high prevalence with atypical symptoms leads to long term delay in establishing the appropriate diagnosis. Further developments in the field of early endometriosis screening will greatly assist clinicians, especially general practitioners in areas with limited health facilities, in early detection of endometriosis.&#x0D; Methods. Using the electronic databases, comprehensive literature searches were conducted with the specific keywords. Full-text manuscripts published were reviewed for relevancy and importantly, reference lists were cross-checked for additional relevant studies.&#x0D; Results. Dysmenorrhea, chronic pelvic pain, dyspareunia, dysuria, dyschezia, and glycoprotein were found dominantly in all analyzed literature. The occurrence of endometriosis affects the functioning of women in multiple aspects of life. Endometriosis places a significant burden on teens and adult women, their families, and society as a whole.&#x0D; Conclusion. Combination of structured past history taking, and several biomarker level might be useful as a screening tool that easy to use and cost effective, as early diagnosis is expected to prevent further progression of endometriosis especially in adolescence.

Menstruation Dysregulation and Endometriosis Development.

Endometriosis is a common gynecological condition characterized by the growth of endometrial-like tissue outside of the uterus which may cause symptoms such as chronic pelvic pain or subfertility. Several surgical and medical therapies are available to manage symptoms, but a cure has yet to be determined which can be attributed to the incomplete understanding of disease pathogenesis. Sampson's theory of retrograde menstruation is a widely accepted theory describing how shed endometrial tissue can enter the peritoneal cavity, but other factors are likely at play to facilitate the establishment of endometriosis lesions. This review summarizes literature that has explored how dysregulation of menstruation can contribute to the pathogenesis of endometriosis such as dysregulation of inflammatory mediators, aberrant endometrial matrix metalloproteinase expression, hypoxic stress, and reduced apoptosis. Overall, many of these factors have overlapping pathways which can prolong the survival of shed endometrial debris, increase tissue migration, and facilitate implantation of endometrial tissue at ectopic sites. Moreover, some of these changes are also implicated in abnormal uterine bleeding and endometrial diseases. More research is needed to better understand the underlying mechanisms driving dysregulation of menstruation in endometriosis specifically and identifying specific pathways could introduce new treatment targets. Analyzing menstrual fluid from women with endometriosis for inflammatory markers and other biomarkers may also be beneficial for earlier diagnosis and disease staging.

Gut microbiota-derived short-chain fatty acids protect against the progression of endometriosis.

Worldwide, ∼196 million are afflicted with endometriosis, a painful disease in which endometrial tissue implants and proliferates on abdominal peritoneal surfaces. Theories on the origin of endometriosis remained inconclusive. Whereas up to 90% of women experience retrograde menstruation, only 10% develop endometriosis, suggesting that factors that alter peritoneal environment might contribute to endometriosis. Herein, we report that whereas some gut bacteria promote endometriosis, others protect against endometriosis by fermenting fiber to produce short-chain fatty acids. Specifically, we found that altered gut microbiota drives endometriotic lesion growth and feces from mice with endometriosis contained less of short-chain fatty acid and n-butyrate than feces from mice without endometriosis. Treatment with n-butyrate reduced growth of both mouse endometriotic lesions and human endometriotic lesions in a pre-clinical mouse model. Mechanistic studies revealed that n-butyrate inhibited human endometriotic cell survival and lesion growth through G-protein-coupled receptors, histone deacetylases, and a GTPase activating protein, RAP1GAP. Our findings will enable future studies aimed at developing diagnostic tests, gut bacteria metabolites and treatment strategies, dietary supplements, n-butyrate analogs, or probiotics for endometriosis.

BAG2-Mediated Inhibition of CHIP Expression and Overexpression of MDM2 Contribute to the Initiation of Endometriosis by Modulating Estrogen Receptor Status.

Endometriosis is an estrogen-dependent gynecological disease primarily affecting women of childbearing age, which gives rise to pelvic pain calling for multiple operations, and sometimes leading to infertility. However, the etiology of endometriosis remains poorly understood. In this study we investigated the roles of two Ubiquitin E3 Ligases, namely hsc70-interacting protein (CHIP) and mouse double minute 2 (MDM2), in the abnormal estrogenic activity in endometriosis. We first collected endometrial tissues from 91 cases of endometriosis and 78 cases of uterine myomas. Next, we established a murine endometriosis model by ectopic endometrial tissue implantation. In other studies, we isolated human endometrial stromal cells (HESCs) were isolated from the endometrial tissues, and performed HA- or FLAG-immunoprecipitation assays and immunoblotting with an anti-ubiquitin antibody to test the interactions among BAG2, CHIP, MDM2, estrogen receptor α (ERα), and ERβ. The expression of ERα was downregulated while that of ERβ, BAG2, and MDM2 was upregulated in human endometriosis and in the mouse model. CHIP degraded ERβ instead of ERα via the ubiquitin-proteasome pathway, while BAG2 impaired the CHIP-mediated degradation of ERβ in cultured HESCs derived from human endometriosis. The degradation of ERα by MDM2 in cultured endometriosis-HESCs also occurred through the ubiquitin-proteasome pathway. Knockdown of both BAG2 and MDM2 alleviated the development of endometriosis in mice. Our findings suggest that the interference of BAG2 and MDM2 may have therapeutic effects in endometriosis. Understanding better the molecular mechanisms underlying the regulation of the abnormal estrogenic activity in endometriosis is crucial for the advancement of targeted therapeutic strategies.

Endometriosis in urology - an update

Introduction: Endometriosis represents the aberrant implantation of endometrial tissue, respectively outside the uterus. It is one of the gynecological diseases with a great impact on the patient’s quality of life and especially on the fertility aspects. Due to the aberrant implantation, this disease can theoretically affect any organ in the abdominal and retroperitoneal cavity. Thus, cases involving the organs of the urinary tract are not a surprise. Material and methods: The present paper focuses on the urological impairment of endometriosis, etiology according to various hypotheses and an update of existing treatment methods. The possible proposals of therapeutic guides found in the literature are also taken into account.Results: The urological condition of this disease seems to increase in frequency in recent years. If in the case of asymptomatic patients an expectant attitude can be approached in relative safety, the local invasive nature of the disease, which can lead to the loss of the function of the various organs of the urinary tract, must not be omitted. In the case of symptomatic patients, the treatment is either hormonal or surgical, lately there is a tendency to combine the two types of treatment. Being a condition with relatively rare urological involvement, the differential diagnosis often omits endometriosis. There are currently several plausible guide proposals, but it takes time and richer casuistry to be able to standardize them. From the point of view of surgical treatment, there is a tendency to introduce robotic surgery in the therapeutic arsenal of this disease, both in the case of classical endometriosis and in the case of urological involvement.

Ultrasound-guided Spinal Needle Localization for Resection of Abdominal Wall Endometrioma

A 47-year-old patient with 2 previous cesarean sections presented with 2 years of right lower quadrant spasm-inducing pain. The pain began with menses and lasted for 15 days each month. Magnetic resonance imaging revealed a 3.3 × 1.9 × 6.0-cm lesion in the medial aspect of the right rectus abdominis muscle, consistent with abdominal wall endometrioma (Fig. 1A). No fascial involvement was identified. At the time of surgery, intraoperative ultrasound was used to map the endometrioma (Fig. 1B). Under ultrasound guidance, the endometrioma borders were marked using 3.5-cm 20 gauge needles through the anterior abdominal wall (Fig. 2). During robotic-assisted excision of the endometrioma, the needles were intermittently advanced and withdrawn from the peritoneal cavity by the bedside assistant to delineate the limits of necessary dissection (Fig. 3). This technique contributed to efficient and complete excision. Postoperatively, the patient reported complete resolution of right lower quadrant pain. Final pathologic evaluation confirmed extensive endometriosis. Abdominal wall endometriosis (AWE) is most often found in previous abdominal surgical incisions. In women undergoing surgical excision of endometriosis, AWE was noted in 1.34% [1Khan Z Zanfagnin V El-Nashar SA Famuyide AO Daftary GS Hopkins MR. Risk factors, clinical presentation, and outcomes for abdominal wall endometriosis.J Minim Invasive Gynecol. 2017; 24: 478-484Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar]. The most common procedure before AWE is cesarean section with a higher risk reported with Pfannenstiel incision vs vertical midline incision [1Khan Z Zanfagnin V El-Nashar SA Famuyide AO Daftary GS Hopkins MR. Risk factors, clinical presentation, and outcomes for abdominal wall endometriosis.J Minim Invasive Gynecol. 2017; 24: 478-484Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar, 2Horton JD Dezee KJ Ahnfeldt EP Wagner M. Abdominal wall endometriosis: a surgeon's perspective and review of 445 cases.Am J Surg. 2008; 196: 207-212Abstract Full Text Full Text PDF PubMed Scopus (184) Google Scholar, 3Zhang P Sun Y Zhang C et al.Cesarean scar endometriosis: presentation of 198 cases and literature review.BMC Womens Health. 2019; 19: 14Crossref PubMed Scopus (23) Google Scholar]. Cesarean scar endometriosis is likely secondary to direct implantation of endometrial tissue in the incision [2Horton JD Dezee KJ Ahnfeldt EP Wagner M. Abdominal wall endometriosis: a surgeon's perspective and review of 445 cases.Am J Surg. 2008; 196: 207-212Abstract Full Text Full Text PDF PubMed Scopus (184) Google Scholar]. Surgical excision allows pathologic evaluation and therapeutic resection [4Karapolat B Kucuk H. A rare cause of abdominal pain: scar endometriosis.Emerg Med Int. 2019; 20192584652Crossref PubMed Google Scholar,5Behbehani S Magtibay P Chen L Wasson M. Clear cell carcinoma of the anterior abdominal wall secondary to iatrogenic endometriosis.J Minim Invasive Gynecol. 2020; 27: 1230-1231Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar]. Excision is often planned with preoperative ultrasound or magnetic resonance imaging. Previously reported surgical approaches to AWE include ablative techniques such as percutaneous cryoablation or ethanol injection [6Welch BT Ehman EC VanBuren WM et al.Percutaneous cryoablation of abdominal wall endometriosis: the Mayo Clinic approach.Abdom Radiol (NY). 2020; 45: 1813-1817Crossref PubMed Scopus (6) Google Scholar]. If AWE involves the fascia, surgical excision can still be performed by a minimally invasive approach with endoscopic mesh placement and fascial repair by general surgery. Intraoperative techniques to assist with excision include injecting the lesion with methylene blue or ultrasound-guided wire localization [7Lee MMH Robson NK Carpenter TT. Ultrasound-guided wired localisation for resection of impalpable anterior abdominal wall scar endometriomas.Gynecol Surg. 2012; 9: 103-105Crossref Scopus (2) Google Scholar,8Takmaz T Kiran G Ozcan P Sahin N Tanoglu B. Total surgical excision by ultrasound–guided wire localization for spontaneous abdominal-wall endometriosis.J Gynecol Surg. 2020; 36: 76-79Crossref Scopus (1) Google Scholar]. Ultrasound-guided localization with spinal needles is a simple, practical technique that can assist with complete excision of abdominal wall endometriomas.

Inhibition of receptor activity-modifying protein 1 suppresses the development of endometriosis and the formation of blood and lymphatic vessels.

Neuroimmune interactions are involved in the development of endometriosis. Here, we examined the role of a neuropeptide, calcitonin gene–related peptide (CGRP), and its receptor, receptor activity–modifying protein (RAMP) 1, in growth of endometrial tissues and the formation of blood and lymphatic vessels in a mouse ectopic endometrial transplantation model. Endometrial fragments from donor wild‐type (WT) mice transplanted into the peritoneal wall of recipient WT mice grew with increased density of blood and lymphatic vessels. When tissues from RAMP1‐deficient (RAMP1−/−) mice were transplanted into RAMP1−/− mice, implant growth and angiogenesis/lymphangiogenesis were decreased. CGRP was up‐regulated in dorsal root ganglia, and CGRP+ nerve fibres were distributed into the implants from the peritoneum. RAMP1 was co‐expressed with CD11b (macrophages) and S100A4 (fibroblasts), but did not co‐localize with blood vessel endothelial cell marker CD31 or lymphatic vessel endothelial hyaluronan receptor (LYVE)‐1. Cultured with CGRP, macrophages up‐regulated vascular endothelial growth factor (VEGF)‐A, VEGF‐C and VEGF‐D, whereas fibroblasts up‐regulated VEGF‐C, but not VEGF‐A or VEGF‐D, in a RAMP1‐dependent manner. CGRP receptor antagonist CGRP8‐37 inhibited growth of and angiogenesis/lymphangiogenesis within endometrial tissue implants. These results suggest that RAMP1 signalling is crucial for growth and angiogenesis/lymphangiogenesis in endometrial tissue. Blockade of RAMP1 is a potential tool for the treatment of endometriosis.

Uncovering Potential Roles of Differentially Expressed Genes, Upstream Regulators, and Canonical Pathways in Endometriosis Using an In Silico Genomics Approach.

Endometriosis is characterized by ectopic endometrial tissue implantation, mostly within the peritoneum, and affects women in their reproductive age. Studies have been done to clarify its etiology, but the precise molecular mechanisms and pathophysiology remain unclear. We downloaded genome-wide mRNA expression and clinicopathological data of endometriosis patients and controls from NCBI’s Gene Expression Omnibus, after a systematic search of multiple independent studies comprising 156 endometriosis patients and 118 controls to identify causative genes, risk factors, and potential diagnostic/therapeutic biomarkers. Comprehensive gene expression meta-analysis, pathway analysis, and gene ontology analysis was done using a bioinformatics-based approach. We identified 1590 unique differentially expressed genes (129 upregulated and 1461 downregulated) mapped by IPA as biologically relevant. The top upregulated genes were FOS, EGR1, ZFP36, JUNB, APOD, CST1, GPX3, and PER1, and the top downregulated ones were DIO2, CPM, OLFM4, PALLD, BAG5, TOP2A, PKP4, CDC20B, and SNTN. The most perturbed canonical pathways were mitotic roles of Polo-like kinase, role of Checkpoint kinase proteins in cell cycle checkpoint control, and ATM signaling. Protein–protein interaction analysis showed a strong network association among FOS, EGR1, ZFP36, and JUNB. These findings provide a thorough understanding of the molecular mechanism of endometriosis, identified biomarkers, and represent a step towards the future development of novel diagnostic and therapeutic options.

Case-control study to develop and validate a questionnaire for the secondary prevention of endometriosis.

BackgroundEndometriosis is a debilitating gynecologic disease characterized by the implantation of endometrial tissue in ectopic locations, with signs of severe and chronic inflammation. The new knowledge on endometriosis has highlighted the value of secondary prevention through the early diagnosis and treatment of lesions to reduce serious consequences, first of all, infertility and chronic pelvic pain. The purpose of this study is to assess the reliability and validity of the questionnaire, as a tool to precociously identify women with endometriosis, to prevent the progression of symptoms.MethodWe reviewed the literature and selected risk factors, symptoms, and phenotypic traits of the women affected by endometriosis to create the questionnaire divided into 8 modules, with 47 questions. A total of 151 women completed the questionnaires: 51 patients who have endometriosis (the cases) and 100 matched women without endometriosis (the controls). After data collection, bivariate and multivariate analyses were conducted.ResultsWe retained four of the significant variables from a step-down logistic regression, namely chronic pelvic pain, dyspareunia with VAS≥3, painful defecation, and acne, to develop a final “predictive” logistic model achieving 90.2% sensitivity and 75% specificity.ConclusionOur pilot study demonstrated that the questionnaire provides a powerful tool for the secondary prevention of endometriosis.

The Suppression Effect of Kebar Extract on Endometriosis Lesion MDA and TNF -a Independent to VEGF A Study in Endometriosis Mice Mode

Background: The pathogenesis of endometriosis remains unclear, and involves multifactorial etiologies. The increase in oxidative stress is known to be associated with this disease. Oxidative stress increases angiogenesis and supports the proliferation of endometriosis tissue in the peritoneal cavity. Kebar grass, a medicinal plant, is expected to increase antioxidant defense resulting in decreased oxidative stress, inflammation, angiogenesis, and reduced endometrial tissue implants.&#x0D; &#x0D; Objective: To investigate the effects of Kebar grass extract administration to MDA serum levels, TNF-a and VEGF expression, and the extension of the endometriotic lesions in mice model.&#x0D; &#x0D; Methods: This study was experimentally designed. It was conducted in the Department of Obstetrics Gynecology, Faculty of Medicine Diponegoro, University and Faculty of Veterinary Medicine, Airlangga University. Twenty-one mice were divided into three groups: the first group is control of 7 untreated endometriosis mice model, the second group consisted of 7 mice injected with leuprolide acetate 1mg/kgBB single dose, and the last group consisted of 7 mice fed with Kebar grass extract 3mg/day for 14 days. MDA serum level was measured by spectrophotometry, TNF-a and VEGF expression by IHC using Rammele Scale Index (ImmunoReactive Score), whereas the extension of the endometriotic lesions was measured using computerize tracing.&#x0D; &#x0D; Results: Both Kebar grass extract and leuprolide acetate administration significantly decrease MDA serum levels in endometriosis mice model, compare with the control group, (0.09±0.02 nmol, 0.11±0.07 nmol, and 0.30±0.06 nmol, respectively; p=0.001). TNF-α expression of the group treated with Kebar grass extract was lower than leuprolide acetate and control group (2.43±1.521 %, 4.86±0.458 %, and 7.26±2.898 %, respectively; p=0.002). However, there was no significant difference in VEGF expression among study groups (4.34±2.40 %, 5.11±1.95 %, and 7.40±3.49 % respectively; p=0.116). Finally, the extension of the endometriotic lesions of the mouse models administered with Kebar grass extract and leuprolide acetate was smaller than the control group (0 mm2, 4.54±7.75 mm2, and 34.80±13.09 mm2 respectively; p=0.005).&#x0D; &#x0D; Conclusion: Kebar grass extract has the effect of decreasing MDA serum levels and reducing TNF-α expression, resulted in smaller endometriotic lesions in mice, even though it does not affect VEGF expression.&#x0D; &#x0D; Keywords: malondialdehyde, tumour necrosis factor alpha, vascular endothelial growth factor, endometriotic lesion, kebar grass extract, endometriosis mouse

Amine oxidase 3 is a novel pro-inflammatory marker of oxidative stress in peritoneal endometriosis lesions

Endometriosis is a common gynaecological disease of women in reproductive age, and is thought to arise from retrograde menstruation and implantation of endometrial tissue, mostly into the peritoneal cavity. The condition is characterized by a chronic, unresolved inflammatory process thereby contributing to pain as cardinal symptom in endometriosis. Elevated reactive oxygen species (ROS) and oxidative stress have been postulated as factors in endometriosis pathogenesis. We here set out for a systematic study to identify novel mechanisms and pathways relating to oxidative stress in ectopic peritoneal lesions. Using combined proteomic and transcriptomic approaches, we identified novel targets including upregulated pro-oxidative enzymes, such as amine oxidase 3/vascular adhesion protein 1 (AOC3/VAP1) as well as downregulated protective factors, in particular alkenal reductase PTGR1 and methionine sulfoxide reductase. Consistent with an altered ROS landscape, we observed hemoglobin / iron overload, ROS production and lipid peroxidation in ectopic lesions. ROS-derived 4-hydroxy-2-nonenal induced interleukin IL-8 release from monocytes. Notably, AOC3 inhibitors provoked analgesic effects in inflammatory pain models in vivo, suggesting potential translational applicability.

Post-caesarean Section Cicatricial Parietal Endometriosis: Case Report and Review of the Literature at the Brazzaville University Hospital (Republic of Congo)

Introduction: Defined as the implantation of endometrial tissue within parietal abdominal structures more superficial than the peritoneum, parietal endometriosis is an exceptional localization of extragenital endometriosis, most often secondary to gynecological obstetric surgery. Clinical observation: We report the case of a 32-year-old patient presenting with an abdominal parietal pain syndrome in comparison with a post-caesarean cutaneous cicatrix, cyclic and rhythmic by menstruation. Ultrasonography of the soft tissues revealed two anterior, heterogeneous hypoechoic nodules with posterior reinforcement. A wide surgery with 1cm of healthy margin allowed the excision of the nodule interesting the subcutaneous tissue and the aponeurosis of the rectus abdominis muscle. The histology was in favour of a focal endometriosis of the abdominal wall extended to the fascia of the rectus muscle. Microscopic examination revealed endometrial glands of variable size, sometimes dilated, bordered by regular cylindrical epithelium, associated with a cytogenic chorion and lymphocytic inflammation, sometimes with blood. Immediate postoperative outcomes were simple. An LHRH analogue protocol (Leuprolide acetate 3.75 mg in one intramuscular injection every 28 days for 6 months) was instituted. Conclusion: Although exceptional, it is appropriate to think of an endometriosis before an abdominal pain syndrome abdominal wall of the woman during periods of genital activity.

An increasing trend of iatrogenic scar endometriosis after lower segment cesarean section

Cesarean scar endometriosis is an uncommon disorder developed due to iatrogenic implantation of endometrial tissues in the cesarean incision site. The frequency of the scar endometriosis is assumed to increase because of the increasing trend of lower segment cesarean section in modern obstetric practice. Cesarean section might be a great risk factor for the development of scar endometriosis due to higher exposure of endometrial cells to the subcutaneous tissue during the procedure. Prevention of decidual cell contamination to the superficial abdominal layers may reduce the occurrence of iatrogenic scar endometriosis. We reported a 21-year old para 2 woman with a history of cesarean section 2.5 years back who presented with a small mass at the middle of the cesarean scar which was associated with pain and blood-stained discharge during menstruation. Based on clinical and USG findings the provisional diagnosis was made scar endometriosis and subsequently we managed her by wide local excision of the lesion followed by adjuvant hormone therapy. No recurrence of scar endometriosis was observed during her follow up period.