Infection as a potential cofactor in the genetic-epigenetic pathophysiology of endometriosis: a systematic review (original) (raw)
Related papers
Endometriosis and the human microbioma
JOURNAL OF CLINICAL SEXOLOGY
The dysbiosis of the intestinal microbiome is associated with various diseases. It is important to understand the factors that influence the intestinal microbiome and the microbiome regulation strategies to increase therapeutic responses. Endometriosis affects about 10% of women of childbearing age. Among those affected by endometriosis, up to 50% of them suffer from chronic pelvic pain and / or infertility. Endometriosis is characterized by inflammation and oestrogen dependence. Endometriosis is a condition that affects fertility, creates a state of "congestion" with an excessive growth of the endometrial tissue in many other areas of the body. The microbiota plays a role in the occurrence of endometriosis by affecting the epigenetic, immunological and / or biochemical functions of the host. Intestinal bacteria are involved in the oestrogen metabolism. The oestrogen-microbiome link (or the stroboloma) helps explain where the excess oestrogen comes from. Endometriosis appears to be associated with the increased presence of Proteobacteria, Enterobacteriaceae, Streptococcus spp. and Escherichia coli in various areas occupied by the microbiome. Further studies are needed to analyse the association between endometriosis and microbiota. Endometriosis is influenced by diet.
Pathogenesis of endometriosis: the genetic/epigenetic theory
Fertility and Sterility
Objective: To study the pathophysiology of endometriosis. Design: Overview of observations on endometriosis. Setting: Not applicable. Patient(s): None. Interventions(s): None. Main Outcome Measure(s): The hypothesis is compatible with all observations. Result(s): Endometriosis, endometrium-like tissue outside the uterus, has a variable macroscopic appearance and a poorly understood natural history. It is a hereditary and heterogeneous disease with many biochemical changes in the lesions, which are clonal in origin. It is associated with pain, infertility, adenomyosis, and changes in the junctional zone, placentation, immunology, plasma, peritoneal fluid, and chronic inflammation of the peritoneal cavity. The Sampson hypothesis of implanted endometrial cells following retrograde menstruation, angiogenic spread, lymphogenic spread, or the metaplasia theory cannot explain all observations if metaplasia is defined as cells with reversible changes and an abnormal behavior/morphology due to the abnormal environment. We propose a polygenetic/polyepigenetic mechanism. The set of genetic and epigenetic incidents transmitted at birth could explain the hereditary aspects, the predisposition, and the endometriosis-associated changes in the endometrium, immunology, and placentation. To develop typical, cystic ovarian or deep endometriosis lesions, a variable series of additional transmissible genetic and epigenetic incidents are required to occur in a cell which may vary from endometrial to stem cells. Subtle lesions are viewed as endometrium in a different environment until additional incidents occur. Typical cystic ovarian or deep endometriosis lesions are heterogeneous and represent three different diseases. Conclusion(s): The genetic epigenetic theory is compatible with all observations on endometriosis. Implications for treatment and prevention are discussed. (Fertil Steril Ò 2019;111:327-40. Ó2018 by American Society for Reproductive Medicine.) El resumen está disponible en Español al final del artículo.
Microbial dysbiosis and disease pathogenesis of endometriosis, could there be a link?
Endometriosis is an estrogen-dependent inflammatory condition in women that is characterised by the ectopic growth of endometrial glands and stroma outside of the uterine cavity. Although there exists many theories for the pathogenesis of endometriosis, none has been successively confirmed as a direct cause for disease development. The human body comprises a diverse microflora across all tissues that can have fundamental roles in health and disease. The microbial flora in a healthy individual can vary remarkably between anatomical sites due to the physical and chemical properties of specific tissues. This includes the female reproductive tract, notably the vagina, which harbors a microbiota dominated by Lactobacilli species. In addition, a core unique microbiome has been defined for the endometrium that also includes Lactobacilli spp. In this review we examine the possibility that endometriosis could result from microbial dysbiosis, whereby significant changes to the natural microflora within the endometrium could reduce mucosal immune regulation in this tissue with concomitant expansion of pathogenic bacteria that trigger local tissue inflammation that could perpetuate the development of endometrial disease.
Ukrainian Scientific Medical Youth Journal
the article presents a review of the literature, which examines the impact of changes in the vaginal microbiome and chronic endometritis on the development of hyperplastic processes of the endometrium in women. Many studies have proven the undoubted role of these factors in the development of endometrial hyperplastic processes, such as atypical hyperplasia and endometrial polyposis. Chronic endometritis, on the background of which there was a course of endometrial hyperplasia, in 95.1% of women studied was caused by an infection of viral, bacterial or fungal origin. Numerous studies indicate the important role of chronic persistent infection in the development of hyperproliferative processes of the endometrium. The largest role in the pathological process is probably played by bacteria of the genus Gardnerella viridans as well as gram-positive cocci (Streptococcus). Herpes simplex virus, cytomegalovirus, human papilloma virus and pathogenic fungi represented by the genus Candida als...
Intra-uterine microbial colonization and occurrence of endometritis in women with endometriosis†
Human reproduction (Oxford, England), 2014
Is there any risk of intra-uterine bacterial colonization and concurrent occurrence of endometritis in women with endometriosis? An increase in intra-uterine microbial colonization and concurrent endometritis occurred in women with endometriosis that was further increased after GnRH agonist (GnRHa) treatment. Higher bacterial contamination of menstrual blood and increased endotoxin level in menstrual and peritoneal fluids have been found in women with endometriosis than in control women. However, information on intra-uterine microbial colonization across the phases of the menstrual cycle and possible occurrence of endometritis in women with endometriosis is still lacking. This is a case-controlled study with prospective collection of vaginal smears/endometrial samples from women with and without endometriosis and retrospective evaluation. Vaginal smears and endometrial smears were collected from 73 women with endometriosis and 55 control women. Twenty of the women with endometriosis...
Endometrial microbiota is more diverse in people with endometriosis than symptomatic controls
Scientific Reports, 2021
Endometriosis is a chronic, estrogen-dependent gynecological condition affecting approximately 10% of reproductive age women. The most widely accepted theory of its etiology includes retrograde menstruation. Recent reports suggest the uterus is not sterile. Thus, the refluxed menstrual effluent may carry bacteria, and contribute to inflammation, the establishment and growth of endometriotic lesions. Here, we compared and contrasted uterine bacteria (endometrial microbiota) in people with surgically confirmed presence (N = 12) or absence of endometriosis (N = 9) using next-generation 16S rRNA gene sequencing. We obtained an average of > 9000 sequence reads per endometrial biopsy, and found the endometrial microbiota of people with endometriosis was more diverse (greater Shannon Diversity Index and proportion of ‘Other’ taxa) than symptomatic controls (with pelvic pain, surgically confirmed absence of endometriosis; diagnosed with other benign gynecological conditions). The relativ...
Fertility and Sterility, 2019
Objective: To systematically compare the endometrial microbiota in infertile women with and without chronic endometritis (CE), as diagnosed by a quantitative and reference range-based method. Design: Case-control observational study. Setting: University-affiliated hospital. Patient(s): One hundred and thirty infertile women. Intervention(s): Endometrial biopsy and fluid (uterine lavage, UL) collected precisely 7 days after LH surge, with plasma cell density (PCD) determined based on Syndecan-1 (CD138)-positive cells in the entire biopsy section and culture-independent massively parallel sequencing of the 16S ribosomal RNA gene performed on both the CE and non-CE endometrial fluid samples. Main Outcome Measure(s): Relative abundance of bacterial taxa. Result(s): Chronic endometritis was diagnosed if the PCD was above the 95th percentile (>5.15 cells per 10 mm 2) of the reference range in fertile control subjects. With this stringent diagnostic criterion, 12 women (9%) were diagnosed with CE. Sequencing was successfully performed on all endometrial samples obtained by UL) (CE, n ¼ 12; non-CE, n ¼ 118). The median relative abundance of Lactobacillus was 1.89% and 80.7% in the CE and non-CE microbiotas, respectively. Lactobacillus crispatus was less abundant in the CE microbiota (fold-change, range: 2.10-2.30). Eighteen non-Lactobacillus taxa including Dialister, Bifidobacterium, Prevotella, Gardnerella, and Anaerococcus were more abundant in the CE microbiota (fold-change, 2.10-18.9). Of these, Anaerococcus and Gardnerella were negatively correlated in relative abundance with Lactobacillus (SparCC correlation magnitude, range: 0.142-0.177). Conclusion(s): Chronic endometritis was associated with a statistically significantly higher abundance of 18 bacterial taxa in the endometrial cavity.
Journal of Pure and Applied Microbiology, 2021
Currently, unlike in the past, the endometrial cavity is not considered to be sterile. The endometrium is supposed to be dominated by Lactobacilli, but also their deficiency can be found in the reproductive tract of asymptomatic healthy women. Sometimes the endometrial microbiome is dominated by various pathological microorganisms, and this can lead to various conditions as chronic endometritis, chorioamnionitis and preterm birth. Their presence causes uterine inflammation and infection, release of pro-inflammatory molecules, uterine contractions, disruption of cervical barrier, premature rupture of membranes. Uterine dysbiosis is associated with recurrent implantation failure and recurrent miscarriages. As the microbiome is important for maintaining immunological homeostasis at the level of gastrointestinal tract Lactobacilli may play a similar function at the level of uterus. The lactobacillus-dominated uterine microbiome is of great importance for maintaining a hostile uterine mi...
Human Reproduction Update, 2020
BACKGROUND: Endometriosis is a gynaecological hormone-dependent disorder that is defined by histological lesions generated by the growth of endometrial-like tissue out of the uterus cavity, most commonly engrafted within the peritoneal cavity, although these lesions can also be located in distant organs. Endometriosis affects ∼10% of women of reproductive age, frequently producing severe and, sometimes, incapacitating symptoms, including chronic pelvic pain, dysmenorrhea and dyspareunia, among others. Furthermore, endometriosis causes .
American Journal of Obstetrics and Gynecology, 2018
BACKGROUND: Chronic endometritis is a persistent inflammation of the endometrial mucosa caused by bacterial pathogens such as Enterobacteriaceae, Enterococcus, Streptococcus, Staphylococcus, Mycoplasma, and Ureaplasma. Although chronic endometritis can be asymptomatic, it is found in up to 40% of infertile patients and is responsible for repeated implantation failure and recurrent miscarriage. Diagnosis of chronic endometritis is based on hysteroscopy of the uterine cavity, endometrial biopsy with plasma cells being identified histologically, while specific treatment is determined based on microbial culture. However, not all microorganisms implicated are easily or readily culturable needing a turnaround time of up to 1 week. OBJECTIVE: We sought to develop a molecular diagnostic tool for chronic endometritis based on real-time polymerase chain reaction equivalent to using the 3 classic methods together, overcoming the bias of using any of them alone. STUDY DESIGN: Endometrial samples from patients assessed for chronic endometritis (n ¼ 113) using at least 1 or several conventional diagnostic methods namely histology, hysteroscopy, and/or microbial culture, were blindly evaluated by real-time polymerase chain reaction for the presence of 9 chronic endometritis pathogens: Chlamydia trachomatis, Enterococcus, Escherichia coli, Gardnerella vaginalis, Klebsiella pneumoniae, Mycoplasma hominis, Neisseria gonorrhoeae, Staphylococcus, and Streptococcus. The sensitivity and specificity of the molecular analysis vs the classic diagnostic techniques were compared in the 65 patients assessed by all 3 recognized classic methods. RESULTS: The molecular method showed concordant results with histological diagnosis in 30 samples (14 double positive and 16 double negative) with a matching accuracy of 46.15%. Concordance of molecular and hysteroscopic diagnosis was observed in 38 samples (37 double positive and 1 double negative), with an accuracy of 58.46%. When the molecular method was compared to microbial culture, concordance was present in 37 samples (22 double positive and 15 double negative), a matching rate of 56.92%. When cases of potential contamination and/or noncultivable bacteria were considered, the accuracy increased to 66.15%. Of these 65 patients, only 27 patients had consistent histological þ hysteroscopic diagnosis, revealing 58.64% of nonconcordant results. Only 13 of 65 patients (20%) had consistent histology þ hysteroscopy þ microbial culture results. In these cases, the molecular microbiology matched in 10 cases showing a diagnostic accuracy of 76.92%. Interestingly, the molecular microbiology confirmed over half of the isolated pathogens and provided additional detection of nonculturable microorganisms. These results were confirmed by the microbiome assessed by next-generation sequencing. In the endometrial samples with concordant histology þ hysteroscopy þ microbial culture results, the molecular microbiology diagnosis demonstrates 75% sensitivity, 100% specificity, 100% positive and 25% negative predictive values, and 0% false-positive and 25% false-negative rates. CONCLUSION: The molecular microbiology method describe herein is a fast and inexpensive diagnostic tool that allows for the identification of culturable and nonculturable endometrial pathogens associated with chronic endometritis. The results obtained were similar to all 3 classic diagnostic methods together with a degree of concordance of 76.92% providing an opportunity to improve the clinical management of infertile patients with a risk of experiencing this ghost endometrial pathology.