AUTHOR=Sunde Jan , Pennington K. A. 
  
TITLE=The uterine secretome initiates growth of gynecologic tissues in ectopic locations: re-evaluating the evidence
  
JOURNAL=Pathology and Oncology Research
  
VOLUME=Volume 32 - 2026
  
YEAR=2026
  
URL=https://www.por-journal.com/journals/pathology-and-oncology-research/articles/10.3389/pore.2026.1612281
  
DOI=10.3389/pore.2026.1612281
  
ISSN=1532-2807
  
ABSTRACT=The origin of ectopic gynecologic lesions has been debated since 1927, when Sampson first proposed retrograde menstruation as the underlying cause of endometriosis. Reproduction in mammals is an unusually permissive process, enabling the implantation of tissue genetically distinct from the mother in which leukemia inhibitory factor (LIF) is known to be a pleiotropic master transcription factor affecting multiple gene pathways such as adhesion and immune tolerance. Herein we review the uterine secretome theory, and how the initial step in ectopic lesion development is implantation. The uterine secretome, which typically cycles every 28–35 days to prepare the endometrium for potential embryo implantation and does so for decades, can be hijacked by free floating cells to implant ectopically when pregnancy does not occur. This review will focus on this emerging theory and its ability to reconcile longstanding gaps in our understanding of both benign and malignant ectopic lesion initiation.