A cross-study gene set enrichment analysis identifies critical pathways in endometriosis

Background  

Endometriosis is an enigmatic disease. Gene expression profiling of endometriosis has been used in several studies, but few studies went further to classify subtypes of endometriosis based on expression patterns and to identify possible pathways involved in endometriosis. Some of the observed pathways are more inconsistent between the studies, and these candidate pathways presumably only represent a fraction of the pathways involved in endometriosis.     

Ubiquitin is associated with the survival of ectopic stromal cells in endometriosis

Background  

Endometriosis is a condition that affects women of reproductive age, where the glandular and/or stromal tissues from the eutopic endometrium implant in ectopic locations. It is well established that the survival of ectopic implants is due to lower levels of apoptosis, but no consensus exists as to which pathway/s this is mediated by. The ubiquitin protein shares a similar sequence homology to an anti-apoptotic protein called BAG-1 and is expressed in the normal endometrium. Currently, no studies have been conducted to determine ubiquitin expression and its possible anti-apoptotic effects in endometriosis.     

Augmented cell survival in eutopic endometrium from women with endometriosis: Expression of c-myc,TGF-beta1 and bax genes

Background  

Endometriosis is a common gynaecological disorder characterized by the presence of endometrial tissue outside of the uterus. The fragments in normal menstruation are composed of necrotic and living cells, which do not survive in ectopic locations because of programmed cell death. The aim of this study was to evaluate if the balance between cell proliferation and apoptosis is changed in eutopic endometrium from women with endometriosis throughout the menstrual cycle by studying bax (pro-apoptotic), c-myc (regulator of cell cycle) and TGF-beta1 (involved in cell differentiation) genes.     

Low-grade appendiceal mucinous neoplasm and endometriosis of the appendix

Background

A distended, mucous-filled appendix is known as an appendiceal mucocele. They are a rare form of an appendiceal mass and develop from both benign and malignant processes. Mucoceles can develop secondarily to an obstruction, such as from a fecalith, scarring or, rarely, endometriosis. Only 12 cases of non-neoplastic appendiceal mucoceles caused by endometriosis have been previously described. The association between neoplastic appendiceal mucoceles in the presence of endometriosis is described for the first time in this report.

Case presentation

A 57-year-old woman presented with a chief complaint of worsening abdominal pain over the past 3 months. Imaging studies revealed an appendiceal mass. Laparoscopic evaluation confirmed an appendiceal mucocele, and the patient underwent complete appendectomy. No evidence of mucinous or endometrial deposits were present within the abdominal cavity. Pathological diagnosis revealed low-grade appendiceal mucinous neoplasm (LAMN) with evidence of endometriosis within the muscularis propria of the appendix. The patient recovered without complications and her abdominal pain completely resolved.

Conclusions

Endometriosis of the appendix is a rare manifestation and is most often identified as an incidental finding. Endometriosis leading to an obstructive mucocele of the appendix is an exceedingly rare finding, having only been described 12 times in the medical literature. LAMN in the presence of endometriosis of the appendix is described for the first time in this report. The association between appendiceal neoplasms in the presence of endometriosis requires further research in order to optimize operative treatment.

     

Metabolomic profiling in follicular fluid of patients with infertility-related deep endometriosis

Introduction

Endometriosis is an estrogen-dependent gynecological disease that causes infertility, and potential metabolomic biomarkers related to ovarian endometriosis and poor outcomes after assisted reproductive treatments are still lacking.

Objectives

The present study analyzed the metabolomic profiling of follicular fluid samples from 40 patients undergoing in vitro fertilization.

Methods

The follicular fluid samples were classified as controls (n = 22) and endometriosis patients (n = 18). The samples were submitted to Bligh and Dyer protocol followed by metabolomics analysis by ultra-performance liquid chromatography mass spectrometry. Clinical data was assessed by Students’ T-test and metabolomics data was analyzed by multivariate statistics by MetaboAnalyst 3.0 to obtain intrinsic characteristics that allowed for groups discrimination. The Receiver Operating Characteristic curve was carried out for the proposed biomarkers, aiming to determine their specificity and sensitivity, as a set and individually.

Results

From the metabolomic analysis, 20 ion masses were selected as potential biomarkers from principal component analysis, which showed that all biomarkers were more abundant in the endometriosis group when compared to controls. Tentative attribution was performed by lipid maps database, demonstrating that these potential biomarkers correspond to fatty acids, carnitines, monoacylglycerols, lysophosphatidic acids, lysophosphatidylglycerols, diacylglycerols, lysophosphatidylcholines, phosphatidylserine, lysophosphatidylinositols and Phosphatidic Acid.

Conclusion

The use of mass spectrometry-based metabolomics allowed for the identification of effective biomarkers for ovarian endometriosis, which may contribute for a better comprehension of the disease and how it affects the ovary, as well as assisting in the development of accessory tools for endometriosis diagnosis and infertility management.

     

The role of DJ-1 in the pathogenesis of endometriosis

Background

Endometriosis is an estrogen-dependent disease causing pelvic pain and infertility in 10% of reproductive-aged women. Despite a long history of the disease the pathogenesis of endometriosis is poorly understood. It is known that the expression of several proteins is either up or down regulated during endometriosis, but their precise role remains to be determined. DJ-1 is one such protein that is upregulated in eutopic endometrium of women having endometriosis suggesting that DJ-1 may be involved in the pathogenesis of endometriosis.

Methodology and Principal Findings

The role of DJ-1 in the pathogenesis of endometriosis was investigated. For this purpose the influence of DJ-1 on endometrial cell survival, attachment, proliferation, migration, and invasion either by overexpressing DJ-1 in normal endometrial cells or by knocking down DJ-1 expression in endometriotic cells using siRNA was investigated. The results indicated that DJ-1 protects endometrial cells from oxidative stress mediated apoptosis. Overexpression of DJ-1 in normal endometrial epithelial cells increases the adhesion on collagen type IV. However, no significant difference was observed incase of stromal cells. It was further demonstrated that DJ-1 regulates cell proliferation, migration, and invasion in normal endometrial and endometriotic epithelial cells whereas in the case of normal endometrial and endometriotic stromal cells, it regulates cell proliferation and invasion but not migration. Furthermore, the present study also indicated that DJ-1 regulates these cellular processes by modulating PI3K/Akt pathway by interacting and negatively regulating PTEN.

Conclusions

Abnormally high levels of DJ-1 expression may be involved in endometriosis, possibly by stimulating endometrial cell survival, proliferation, migration, and invasion.     

Mitochondrial genome variations in advanced stage endometriosis: a study in South Indian population

Background

Endometriosis is a chronic gynecological benign disease that shares several features similar to malignancy. Mitochondrial DNA (mtDNA) mutations have been reported in all most all types of tumors. However, it is not known as to whether mtDNA mutations are associated with endometriosis.

Methodology

We sequenced the entire mitochondrial genome of analogous ectopic and eutopic endometrial tissues along with blood samples from 32 advanced stage endometriosis patients to analyze the role of somatic and germ-line mtDNA variations in pathogenesis of endometriosis. All ectopic tissues were screened for tumor-specific mtDNA deletions and microsatellite instability (MSI). We also performed mtDNA haplogrouping in 128 patients and 90 controls to identify its possible association with endometriosis risk.

Principal Findings

We identified 51 somatic (novel: 31; reported: 20) and 583 germ-line mtDNA variations (novel: 53; reported: 530) in endometriosis patients. The A13603G, a novel missense mutation which leads to a substitution from serine to glycine at the codon 423 of ND5 gene showed 100% incidence in ectopic tissues. Interestingly, eutopic endometrium and peripheral leukocytes of all the patients showed heteroplasmy (A/G; 40–80%) at this locus, while their ectopic endometrium showed homoplasmic mutant allele (G/G). Superimposition of native and mutant structures of ND5 generated by homology modeling revealed no structural differences. Tumor-specific deletions and MSI were not observed in any of the ectopic tissues. Haplogrouping analysis showed a significant association between haplogroup M5 and endometriosis risk (P: 0.00069) after bonferroni correction.

Conclusions

Our findings substantiate the rationale for exploring the mitochondrial genome as a biomarker for the diagnosis of endometriosis.     

Laparoscopic conservative management of ureteral endometriosis: a survey of eighty patients submitted to ureterolysis

Background  

this study aims to evaluate the effectiveness and safety of laparoscopic conservative management of ureteral endometriosis.     

Family incidence of endometriosis in first-, second-, and third-degree relatives: case-control study

Background  

Initial publications examining the hereditary aspects of endometriosis appeared in the early seventies and demonstrated an up to seven-fold risk for endometriosis in first-degree relatives of endometriosis patients. The aim was to evaluate the influence of hereditary aspects on the endometriosis risk in our patient collective.     

Laser capture microdissection and cDNA array analysis of endometrium identify CCL16 and CCL21 as epithelial-derived inflammatory mediators associated with endometriosis

Background  

Understanding the pathophysiology of chemokine secretion in endometriosis may offer a novel area of therapeutic intervention. This study aimed to identify chemokines differentially expressed in epithelial glands in eutopic endometrium from normal women and those with endometriosis, and to establish the expression profiles of key chemokines in endometriotic lesions.     

Modified gateway system for double shRNA expression and Cre/lox based gene expression

Background  

The growing need for functional studies of genes has set the stage for the development of versatile tools for genetic manipulations.     

Women with endometriosis improved their peripheral antioxidant markers after the application of a high antioxidant diet

Background  

Oxidative stress has been identified in the peritoneal fluid and peripheral blood of women with endometriosis. However, there is little information on the antioxidant intake for this group of women. The objectives of this work were 1) to compare the antioxidant intake among women with and without endometriosis and 2) to design and apply a high antioxidant diet to evaluate its capacity to reduce oxidative stress markers and improve antioxidant markers in the peripheral blood of women with endometriosis.     

A systematic approach for testing expression of human full-length proteins in cell-free expression systems

Background  

The growing field of proteomics and systems biology is resulting in an ever increasing demand for purified recombinant proteins for structural and functional studies. Here, we show a systematic approach to successfully express a full-length protein of interest by using cell-free and cell-based expression systems.     

Resolution of large and small differences in gene expression using models for the Bayesian analysis of gene expression levels and spotted DNA microarrays

Background  

The detection of small yet statistically significant differences in gene expression in spotted DNA microarray studies is an ongoing challenge. Meeting this challenge requires careful examination of the performance of a range of statistical models, as well as empirical examination of the effect of replication on the power to resolve these differences.     

TiGER: A database for tissue-specific gene expression and regulation

Background  

Understanding how genes are expressed and regulated in different tissues is a fundamental and challenging question. However, most of currently available biological databases do not focus on tissue-specific gene regulation.     

Washing scaling of GeneChip microarray expression

Background  

Post-hybridization washing is an essential part of microarray experiments. Both the quality of the experimental washing protocol and adequate consideration of washing in intensity calibration ultimately affect the quality of the expression estimates extracted from the microarray intensities.     

Identification and expression analysis of genes associated with bovine blastocyst formation

Background  

Normal preimplantation embryo development encompasses a series of events including first cleavage division, activation of the embryonic genome, compaction and blastocyst formation.     

Simultaneous tracking of fly movement and gene expression using GFP

Background  

Green Fluorescent Protein (GFP) is used extensively as a reporter for transgene expression in Drosophila and other organisms. However, GFP has not generally been used as a reporter for circadian patterns of gene expression, and it has not previously been possible to correlate patterns of reporter expression with 3D movement and behavior of transgenic animals.     

OCT-4 expression in follicular and luteal phase endometrium: a pilot study

Background  

The stem cell marker Octamer-4 (OCT-4) is expressed in human endometrium. Menstrual cycle-dependency of OCT-4 expression has not been investigated to date.