Cela Vito, Malacarne Elisa, Obino Maria Elena Rosa, Marzi Ilaria, Papini Francesca, Vergine Francesca, Pisacreta Elena, Zappelli Elisa, Pietrobono Deborah, Scarfò Giorgia, Daniele Simona, Franzoni Ferdinando, Martini Claudia, Artini Paolo Giovanni
Division of Gynecology and Obstetrics, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy.
Department of Pharmacy, University of Pisa, 56126 Pisa, Italy.
Biomedicines. 2021 Nov 12;9(11):1681. doi: 10.3390/biomedicines9111681.
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.
子宫内膜异位症（EMS）的发病机制与腹膜液中炎症介质的释放有关，从而产生一种改变的微环境，导致低质量的卵母细胞/胚胎，并降低着床率。上皮-间质转化（EMT）是一个与炎症相关的过程，可能是EMS的另一个促成因素。本研究旨在调查各种细胞因子和EMT标志物（钙黏蛋白、转化生长因子-β、缺氧诱导因子-1α）中，哪些是EMS的诊断标志物以及体外受精（IVF）结果的预后因素。在此，EMS患者表现出血清中炎症分子白细胞介素-6（IL-6）、白细胞介素-8（IL-8）和白细胞介素-12水平较高，而抗炎性白细胞介素-10的浓度降低。此外，与EMT过程相关的生化标志物在EMS患者的血清和卵泡液（FF）中比对照组中升高得更多。最后，优质胚胎的数量与血清IL-6和EMT标志物呈负相关。有趣的是，血清IL-6和FF中IL-10的浓度可区分EMS患者和对照组。最后，血清IL-8和E-钙黏蛋白水平以及FF中的IL-10能非常准确地预测IVF的阳性结果。我们的数据证实了炎症介质（即IL-6和IL-10）在EMS发病机制中的关键作用，并表明与EMT相关的标志物在EMS患者中升高，且可预测IVF结果。
