# The uterine secretome initiates growth of gynecologic tissues in ectopic locations: re-evaluating the evidence

## TL;DR

This paper reviews a new theory about how gynecologic tissues can grow in the wrong places, suggesting that the uterine secretome plays a key role in this process.

## Contribution

The paper introduces the uterine secretome theory as a novel explanation for ectopic lesion initiation.

## Key findings

- The uterine secretome can be hijacked by free-floating cells to cause ectopic implantation.
- Leukemia inhibitory factor (LIF) is a key player in processes like adhesion and immune tolerance.
- The theory helps explain gaps in understanding both benign and malignant ectopic lesions.

## 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.