A mechanometabolic founder fragment model for endometriosis initiation

This Perspective proposes a mechanometabolic “founder fragment” model to explain why endometriosis is rare despite common retrograde menstruation, focusing on the selection of rare intact epithelial–stromal tissue fragments from refluxed menstrual effluent. It argues that cervical impedance and dysperistalsis may promote focal fragment generation and retrograde delivery, while fallopian-tube transit may further select fragments that preserve architecture, have survival competence, and provide stromal permissiveness. The paper lays out testable translational predictions, including menstrual-effluent profiling, peristalsis imaging, and stretch priming, with a central prediction of an endometriosis-associated shift in the architecture-preserved mechanical survival fraction of fragments under a standardized confinement-and-pulsatile-shear challenge after adjusting for total menstrual volume. This paper is centrally about endometriosis initiation — it develops and specifies a founder-fragment mechanometabolic model driven by mechanics, transit, and survival of selected menstrual-effluent fragments.

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