25 August 2021
Is there a causative relation?
Endometriosis is the chronic inflammation of the endometrium, the cellular lining of the uterus. It is considered a chronic gynecological disease and it is more common than you think!
Globally, 5–10% of the women of reproductive age are affected by endometriosis.
Nowadays, it is considered a systematic illness that is not confined in the uterus. It appears to affect the whole pelvic area, changes the metabolism in the liver and adipose tissue, leading to systemic inflammation, and alters gene expression in the brain area responsible for pain sensitization and mood disorders. Now that the focus has shifted from the female reproductive organs to a more holistic approach, new studies are undertaken to assess the impact of this disease on human well-being.1Moreover, the connection of infertility and endometriosis renders the latter an obvious target for assisted reproduction.
Possible causes of Chronic Endometriosis
The endometrium changes its consistency, by thickening, following the menstrual cycle of the woman, in response to the increase/decrease of female hormones (oestrogen and progesterone). During pregnancy, the placenta derives from this cell group to surround, protect, and feed the foetus. Some theories believe that this very adaptability of the endometrium to the women’s life cycle is the source of endometriosis.
Some researchers believe that endometrial cell shedding or stem cells regeneration during menstruation can lead those cells to migrate to ectopic regions and cause abnormal growth. Others speculate that hormonal imbalances influence the development of the disease and link it to the observed progesterone resistance. Other theories blame the genetics or faulty lymphatic drainage, based on the familial predominance of endometriosis. Some scientists consider developmental faults in the fallopian tubes’ organogenesis or dysfunctional uterine peristalsis. Oxidative stress, inflammation and apoptosis, normal cellular processes, have also been implicated; While one theory does not exclude the other, it seems that the etiology is multifactorial and needs further investigation.
Infection and Chronic Endometriosis
Infection is considered one major causative of endometriosis because of the immune and oxidative responses it can trigger, as well as the apoptotic events if the infection is not adequately managed. Moreover, chronic infection induces epigenetic alterations to the afflicted tissues that modulate gene expression, further triggering endometriosis and can lead even to carcinogenesis.
Endometriosis appears to be associated with an increased presence of Proteobacteria, Enterobacteriaceae, Streptococcus spp. and Escherichia coli across various microbiome sites. The phylum Firmicutes and the genus Gardnerella also appear to have an association. Women with endometriosis have higher concentrations of Escherichia Coli and higher concentrations of bacterial endotoxins in menstrual blood. In stool samples Shigella/Escherichia are predominately detected. The endometrium is usually infected by Gardnerella, Streptococcus, Enterococci and Escherichia coli.
While other factors that influence or impact endometriosis cannot be predicted, infection is one risk factor that is both avoidable and treatable. Asymptomatic chronic infection can lead to chronic endometriosis. The early and reliable detection of endometrial pathogens is of paramount importance for women’s health care and routine diagnostics.
Micronbrane Medical provides the solution with two products: Devin® and PaRTI-Seq® (Pathogen Real-Time Identification by Sequencing). Devin® membrane produces pathogen-enriched samples ready for downstream diagnostic applications. PaRTI-Seq® technology combines the latest third-generation sequencing (Nanopore Sequencing) and proprietary analytical methods, aiming to provide the test results within 24 hours.
- Taylor HS, Kotlyar AM, Flores VA. Endometriosis is a chronic systemic disease: clinical challenges and novel innovations. The Lancet. 2021;397(10276):839-852. doi:10.1016/S0140-6736(21)00389-5
- Tomassetti C, D’Hooghe T. Endometriosis and infertility: Insights into the causal link and management strategies. Best Pract Res Clin Obstet Gynaecol. 2018;51:25-33. doi:10.1016/j.bpobgyn.2018.06.002
- Cousins FL, Pandoy R, Jin S, Gargett CE. The Elusive Endometrial Epithelial Stem/Progenitor Cells. Front Cell Dev Biol. 2021;9:640319. doi:10.3389/fcell.2021.640319
- Donnez J, Dolmans M-M. Endometriosis and Medical Therapy: From Progestogens to Progesterone Resistance to GnRH Antagonists: A Review. J Clin Med. 2021;10(5). doi:10.3390/jcm10051085
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- Hill CJ, Fakhreldin M, Maclean A, et al. Endometriosis and the Fallopian Tubes: Theories of Origin and Clinical Implications. J Clin Med. 2020;9(6). doi:10.3390/jcm9061905
- Agostinis C, Balduit A, Mangogna A, et al. Immunological Basis of the Endometriosis: The Complement System as a Potential Therapeutic Target. Front Immunol. 2021;11. doi:10.3389/fimmu.2020.599117
- Laganà AS, Garzon S, Götte M, et al. The Pathogenesis of Endometriosis: Molecular and Cell Biology Insights. Int J Mol Sci. 2019;20(22). doi:10.3390/ijms20225615
- Kobayashi H, Higashiura Y, Shigetomi H, Kajihara H. Pathogenesis of endometriosis: The role of initial infection and subsequent sterile inflammation (Review). Mol Med Rep. 2014;9(1):9-15. doi:10.38 https://pubmed.ncbi.nlm.nih.gov/24173432/92/mmr.2013.1755
- Koninckx PR, Ussia A, Tahlak M, et al. Infection as a potential cofactor in the genetic-epigenetic pathophysiology of endometriosis: a systematic review. Facts Views Vis ObGyn. 2019;11(3):209-216.
- Leonardi M, Hicks C, El-Assaad F, El-Omar E, Condous G. Endometriosis and the microbiome: a systematic review. BJOG Int J Obstet Gynaecol. 2020;127(2):239-249. doi:10.1111/1471-0528.15916