REVIEW
Pathol. Oncol. Res.
The uterine secretome initiates growth of gynecologic tissues in ectopic locations: re-evaluating the evidence
- JS
Jan Sunde 1
- KP
Kathleen Pennington 2
1. Baylor College of Medicine, Division of Gynecologic Oncology, Houston, United States
2. Baylor College of Medicine, Houston, United States
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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.
Summary
Keywords
endosalpingiosis, endometriosis, implantation, ovarian cancer, uterine secretome
Received
30 September 2025
Accepted
29 January 2026
Copyright
© 2026 Sunde and Pennington. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Jan Sunde
Disclaimer
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