Abstract
Endometriosis (EMS) pathogenesis has been related to the release of inflammatory mediators in peritoneal fluid, creating an altered microenvironment that leads to low-grade oocyte/embryos and to the reduction of implantation rates. The Epithelial–Mesenchymal Transition (EMT), an inflammation-related process, can be a further contributing factor to EMS. This study aimed to investigate, among various cytokines and EMT markers (Cadherins, TGF-β, HIF-1α), diagnostic markers of EMS and prognostic factors of in vitro fertilization (IVF) outcomes. Herein, EMS patients manifested higher serum levels of the inflammatory molecules IL-6, IL-8, and IL-12 and a decrease in the concentrations of the anti-inflammatory IL-10. Moreover, biochemical markers associated with the EMT process were more elevated in serum and follicular fluid (FF) of EMS patients than in controls. At the end, the number of good-quality embryos was inversely related to serum IL-6 and EMT markers. Interestingly, serum IL-6 and FF IL-10 concentrations differentiated EMS patients from controls. Finally, serum IL-8 and E-Cadherin levels, as well as FF IL-10, predicted positive IVF outcome with great accuracy. Our data confirm the pivotal role of inflammatory mediators (i.e., IL-6 and IL-10) in EMS pathogenesis and suggest that EMT-related markers are elevated in EMS patients and can be predictive of IVF outcome.
Highlights
Introduction published maps and institutional affilEndometriosis (EMS) is an estrogen-dependent chronic and progressive inflammatory disease that is characterized by the growth of endometrial-like tissue outside the uterine cavity [1]
The present study aimed to investigate, among various inflammatory factors, key serum and intrafollicular markers to differentiate control women from EMS patients and to predict good-quality oocytes/embryos in women undergoing in vitro fertilization (IVF)
The main findings of our study are as follows: (i) EMS patients presented significantly higher serum levels of the inflammatory molecules IL-6, IL-8, and IL-12 and a decreased concentration of the anti-inflammatory marker IL-10 compared to control women; (ii) biochemical markers associated with the Epithelial–Mesenchymal Transition (EMT) process (i.e, N-cadherin, NF-kB, Transforming Growth Factor β (TGF-β), and HIF-1α) were significantly more elevated in serum and/or follicular fluid (FF) of EMS patients than in control women
Summary
Endometriosis (EMS) is an estrogen-dependent chronic and progressive inflammatory disease that is characterized by the growth of endometrial-like tissue outside the uterine cavity [1]. The pathogenesis of these ectopic alterations lies in a multifactorial process that involves genetic and epigenetic factors, hormones, persistent peritoneal menstrual reflux, and exogenous factors [2]. Considering reproductive age, it affects 10–15% of all women and 30% of infertile women, with various symptoms including dyspareunia, dysmenorrhea, pelvic pain, headache, abdominal pain, and mood disorders [3]. Morphological alterations and a decrease in cytoplasmic mitochondrial content impair oocyte quality in women affected by iations.
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