Background: Endometriosis is a multifactorial disease that mainly affects women of reproductive age. The exact pathogenesis of this disease is still debatable. The role of bacterial endotoxin (lipopolysaccharide, LPS) and Toll-like receptor 4 (TLR4) in endometriosis were investigated and the possible source of endotoxin in the pelvic environment was examined.
Methods: The limulus amoebocyte lysate test was used to measure the endotoxin levels in the menstrual fluid and peritoneal fluid and their potential role in the growth of endometriosis was investigated. Menstrual blood and endometrial samples were cultured for the presence of microbes. The effect of gonadotrophin-releasing hormone agonist (GnRHa) treatment on intrauterine microbial colonization (IUMC) and the occurrence of endometritis was investigated.
Main Findings Results: Lipopolysaccharide regulates the pro-inflammatory response in the pelvis and growth of endometriosis via the LPS/TLR4 cascade. The menstrual blood was highly contaminated with and the endometrial samples were colonized with other microbes. A cross-talk between inflammation and ovarian steroids or the stress reaction also was observed in the pelvis. Treatment with GnRHa further worsens intrauterine microbial colonization, with the consequent occurrence of endometritis in women with endometriosis.
Conclusion: For the first time, a new concept called the "bacterial contamination hypothesis" is proposed in endometriosis. This study's findings of IUMC in women with endometriosis could hold new therapeutic potential in addition to the conventional estrogen-suppressing agent.
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http://dx.doi.org/10.1002/rmb2.12083 | DOI Listing |
Pharmaceuticals (Basel)
January 2025
Department of Drug Form Technology, Wroclaw Medical University, Borowska 211 A, 50-556 Wroclaw, Poland.
Introduction: The official implementation of pharmaceutical-grade cannabis raw materials for medicinal use has permitted doctors to prescribe and pharmacists to prepare cannabis-based formulations. The objective of the pharmaceutical development and manufacturing process optimization work was to propose a suppository formulation containing doses of 25 mg and 50 mg of tetra-hydrocannabinol (∆-9-THC) as an alternative to existing inhalable or orally administered formulations. The formulation could be used for rectal or vaginal administration, thereby providing dosage control in the treatment of endometriosis and other conditions involving pain.
View Article and Find Full Text PDFPharmaceuticals (Basel)
December 2024
College of Pharmacy, University of Illinois, Chicago, IL 60612, USA.
Overexpression of the gonadotropin-releasing hormone receptor (GnRH-R) plays a vital role in the advancement of reproductive malignancies such as ovarian, endometrial, and prostate cancer. Peptidomimetic GnRH antagonists are a substantial therapeutic development, providing fast and reversible suppression of gonadotropins by directly blocking GnRH-R. Unlike typical GnRH agonists, these antagonists prevent the early hormonal flare, have a faster onset of action, and have a lower risk of cardiovascular problems.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Service d'Anatomie Pathologique, Institut Mutualiste Montsouris, 42 Bd Jourdan, 75014 Paris, France.
Abdominal wall endometriosis (AWE) is a clinical disorder with unknown pathogenesis with an incidence between 0.03% and 1% in women affected by cutaneous/scar endometriosis. We investigated the pathological, molecular cytogenetic and cell proliferation features of a primary AWE developed in rectus abdominis muscle in a patient without co-existing pelvic endometriosis.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Women's Centre, Oxford OX3 9DU, UK.
Endometriosis is a chronic inflammatory condition characterised by the presence of endometrium-like tissue outside the uterus. Despite its high prevalence and recent advances in molecular science, many aspects of endometriosis and its pathophysiology are still poorly understood. Previously, in vitro and in vivo modelling have been instrumental in establishing our current understanding of endometriosis.
View Article and Find Full Text PDFBiomolecules
January 2025
ENDOLIFE, 28 Rue de Courcelles, 75008 Paris, France.
Endometriosis is a chronic, estrogen-dependent disorder associated with the presence of endometrial cells mainly in the pelvic cavity, causing systemic immune inflammation, infertility, epigenetic dysregulation of differential DNA methylation, coelomic metaplasia, and pain. It affects approximately 10-12% of women. Despite decades of research, full pathophysiology, a diagnostic roadmap, and clinical management strategies for endometriosis are not yet fully elucidated.
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