Cellular Phenotypic Changes in Endometriosis: Pathogenetic Mechanisms and Therapeutic Implications

Jingyi Zhang,1 Yiyun Bai,1 Sang Luo,2 Yiran Jin,2 Dan Liu2– 41The First Clinical Medical College, Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 2Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 3Department of Gynecology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 4Key Laboratory of Ministry of Education for Fertility Preservation and Maintenance, Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of ChinaCorrespondence: Dan Liu, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China, Tel +86-13995285699, Email [email protected]: Endometriosis is a common gynecological disorder characterized by extra-uterine growth of endometrial-like tissues, which causes chronic inflammation, pelvic pain and infertility and greatly impairs patients’ quality of life. Despite its high prevalence, the exact pathogenesis of endometriosis remains incompletely understood and clinical therapeutic options are still limited. This paper is a combined narrative-bibliometric review. It systematically summarizes the roles and molecular mechanisms of multiple cellular phenotypic alterations including hypoxic microenvironment, aberrant cell proliferation, dysregulated autophagy, pyroptosis, ferroptosis and epithelial-mesenchymal transition (EMT) in the pathogenesis of endometriosis. Bibliometric analyses were performed based on the Web of Science Core Collection for each sub-theme, with dozens to hundreds of English-language publications included to assist in identifying research hotspots. By integrating evidence from in-vitro cellular experiments, animal models and human tissue studies, this review illustrates the interconnections among these cellular phenotypes, provides theoretical references for understanding the pathophysiology of endometriosis, and discusses corresponding translational and therapeutic implications.Keywords: endometriosis, hypoxia, cell proliferation, autophagy, pyroptosis, ferroptosis, epithelial-mesenchymal transition