Pathogenesis of endometriosis: the role of genetics, inflammation and oxidative stress.
ABSTRACT Endometriosis is defined as the presence of endometrial tissue outside the uterine cavity.
The etiology of this multifactorial disease is still unresolved and an increasing number of studies suggest that genetic, hormonal, environmental, immunological and oxidative factors may all play an important role in the pathogenesis of this disorder.
In this literature review, inflammatory activity, oxidative stress as well as genetic abnormalities and mutations have been studied in an effort to identify factors predisposing to endometriosis.
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ABSTRACT: What is the potential impact of follicular fluid (FF) from infertile women with mild endometriosis (ME) on oocyte quality, especially on nuclear maturation and the meiotic spindle? FF from infertile women with ME may compromise nuclear maturation and the meiotic spindles of in vitro matured bovine oocytes. Controversial studies have suggested that impaired oocyte quality may be involved in the pathogenesis of endometriosis-related infertility. Moreover, some studies have demonstrated alterations in the composition of FF from infertile women with endometriosis. However, to date no study has evaluated the effect of FF from infertile women with ME on the genesis of meiotic oocyte anomalies. We performed an experimental study. Samples of FF were obtained from February 2009 to February 2011 from 22 infertile women, 11 with ME and 11 with tubal or male factors of infertility (control group), who underwent ovarian stimulation for ICSI at our university IVF Unit. From March 2011 to February 2012 we performed in vitro maturation (IVM) experiments using immature bovine oocytes as described below. FF free of blood and containing a mature oocyte was obtained from 22 infertile women during oocyte retrieval for ICSI. Immature bovine oocytes underwent IVM in the absence of FF (No-FF) and in the presence of four concentrations (1, 5, 10 and 15%) of FF from infertile women without endometriosis (C-FF) and with ME (ME-FF). Eleven replicates were performed, each one using FF from a control patient and a patient with ME. Each FF sample was used in only one experiment. After 22-24 h of IVM, oocytes were denuded, fixed and immunostained for morphological visualization of microtubules and chromatin by confocal microscopy. A total of 1324 cumulus-oocyte complexes were matured in vitro. Of these, 1128 were fixed and 1048 were analyzed by confocal microscopy. The percentage of meiotically normal oocytes was significantly higher for oocytes that underwent IVM in the absence of FF (No-FF; 76.5%) and in the presence of 1% (80.9%), 5% (76.6%), 10% (75%) and 15% (76.2%) C-FF than in oocytes that underwent IVM in the presence of 1% (44.4%), 5% (36.7%), 10% (45.5%) and 15% (51.2%) ME-FF (P < 0.01). No differences were observed among FF concentrations within each group. When the four concentrations from each group were pooled, the number of oocytes in metaphase I stage was significantly higher in the ME-FF (50 oocytes) than in the C-FF (29 oocytes) group and the percentage of meiotic abnormalities was significantly higher when oocytes were matured with ME-FF (55.8%) than with C-FF (23.1%), P < 0.01. Owing to the strict selection criteria for FF donors, this study had a small sample size (11 cases and 11 controls), and thus further investigations using a large cohort of patients are needed to confirm these results. In addition, data obtained from studies using animal models may not necessarily be extrapolated to humans and studies evaluating in vivo matured oocytes from infertile women with ME are important to confirm our results. Our results open new insights into the pathogenic mechanisms of infertility related to mild endometriosis, suggesting that FF from infertile women with mild endometriosis may be involved in the worsening of oocyte quality of these women. This study was supported by the National Council for Scientific and Technological Development (CNPq), Brazil. The authors declare no conflicts of interest.Human Reproduction 10/2013; · 4.67 Impact Factor
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ABSTRACT: Human endometrium is a highly dynamic tissue, undergoing periodic growth and regression at each menstrual cycle. Endometriosis is a frequent chronic pathological status characterized by endometrial tissue with an ectopic localization, causing pelvic pain and infertility and a variable clinical presentation. In addition, there is well-established evidence that, although endometriosis is considered benign, it is associated with an increased risk of malignant transformation in approximately 1.0% of affected women, with the involvement of multiple pathways of development. Increasing evidence supports a key contribution of different stem/progenitor cell populations not only in the cyclic regeneration of eutopic endometrium, but also in the pathogenesis of at least some types of endometriosis. Evidence has arisen from experiments in animal models of disease through different kinds of assays (including clonogenicity, the label-retaining cell approach, the analysis of undifferentiation markers), as well as from descriptive studies on ectopic and eutopic tissue samples harvested from affected women. Changes in stem cell populations in endometriotic lesions are associated with genetic and epigenetic alterations, including imbalance of miRNA expression, histone and DNA modifications and chromosomal aberrations. The present short review mainly summarizes the latest observations contributing to the current knowledge regarding the presence and the potential contribution of stem/progenitor cells in eutopic endometrium and the aetiology of endometriosis, together with a report of the most recently identified genetic and epigenetic alterations in endometriosis. We also describe the potential advantages of single cell molecular profiling in endometrium and in endometriotic lesions. All these data can have clinical implications and provide a basis for new potential therapeutic applications.Clinical Science 01/2014; 126(2):123-38. · 4.86 Impact Factor
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ABSTRACT: Particulate matter and proximity to large roadways may promote disease mechanisms, including systemic inflammation, hormonal alteration, and vascular proliferation, that may contribute to the development and severity of endometriosis. To determine the association of air pollution exposures during adulthood, including distance to road, particulate matter less than 10 microns, less than 2.5 microns, and between 2.5 and 10 microns (PM2.5, PM10-2.5, PM10), and timing of exposure with risk of endometriosis in the Nurses' Health Study II. Proximity to major roadways and outdoor levels of PM2.5, PM10-2.5, PM10 were determined for all residential addresses from 1993 to 2007. Multivariable-adjusted time-varying Cox proportional hazard models were used to estimate the relation between these air pollution exposures and endometriosis risk. Among 84,060 women 2,486 incident cases of surgically confirmed endometriosis were identified over 710,230 person-years of follow-up. There was no evidence of an association, between distance to road, PM2.5, PM10-2.5, PM10 averaged over follow-up or during the previous 2- or 4- year period and endometriosis risk. Traffic and air pollution exposures during adulthood were not associated with incident endometriosis in this cohort of women.Environmental Health Perspectives 11/2013; · 7.26 Impact Factor