Wilson Taylor R, Peterson Kurt R, Morris Stephanie A, Kuhnell Damaris, Kasper Susan, Burns Katherine A
Division of Environmental Genetics and Molecular Toxicology, Department of Environmental and Public Health Sciences, and.
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
JCI Insight. 2025 Jan 21;10(5):e186133. doi: 10.1172/jci.insight.186133.
Endometriosis is a chronic gynecological disease that affects 1 in 10 reproductive-aged women. Most studies investigate established disease; however, the initiation and early events in endometriotic lesion development remain poorly understood. Our study used neutrophils from human menstrual effluent from patients with and without endometriosis for immunophenotyping, and it used a mouse model of endometriosis and a mouse endometriosis cell line to determine the role of neutrophils in the initiating events of endometriosis, including attachment and survival of minced endometrial pieces. In menstrual effluent from women with endometriosis, the ratios of aged and proangiogenic neutrophils increased compared with controls, indicating a potentially permissive proinflammatory microenvironment. In our endometriosis mouse model, knocking down neutrophil recruitment with α-CXCR2 into the peritoneum decreased endometrial tissue adhesion - supported by decreased levels of myeloperoxidase and neutrophil elastase in both developing lesions and peritoneal fluid. Fibrinogen was identified as the preferred substrate for endometrial cell adhesion in an in vitro adhesion assay and in developing lesions in vivo. Together, aged and proangiogenic neutrophils and their secretions likely promote attachment and formation of endometriotic lesions by releasing neutrophil extracellular traps and upregulating fibrinogen expression as a provisional matrix to establish attachment and survival in the development of endometriosis lesions.
子宫内膜异位症是一种慢性妇科疾病，影响着十分之一的育龄妇女。大多数研究调查的是已确诊的疾病；然而，子宫内膜异位症病变发展的起始和早期事件仍知之甚少。我们的研究使用患有和未患有子宫内膜异位症患者月经流出液中的中性粒细胞进行免疫表型分析，并使用子宫内膜异位症小鼠模型和小鼠子宫内膜异位症细胞系来确定中性粒细胞在子宫内膜异位症起始事件中的作用，包括切碎的子宫内膜碎片的附着和存活。在患有子宫内膜异位症女性的月经流出液中，与对照组相比，衰老和促血管生成的中性粒细胞比例增加，表明存在潜在的促炎微环境。在我们的子宫内膜异位症小鼠模型中，通过α-CXCR2抑制中性粒细胞向腹膜的募集可减少子宫内膜组织粘连，这在发育中的病变和腹膜液中髓过氧化物酶和中性粒细胞弹性蛋白酶水平降低得到了支持。在体外粘附试验和体内发育中的病变中，纤维蛋白原被确定为子宫内膜细胞粘附的首选底物。总之，衰老和促血管生成的中性粒细胞及其分泌物可能通过释放中性粒细胞胞外陷阱和上调纤维蛋白原表达作为临时基质来促进子宫内膜异位症病变的附着和形成，从而在子宫内膜异位症病变的发展中建立附着和存活。
