ABSTRACT
OBJECTIVE: To evaluate the effects of the cannabinoid system on the regulation of endometrial stromal cell (ESCs) dynamic behavior. DESIGN: ESC migration, electrical signal generated by K(+) channels, and cytoskeletal-actin dynamics were evaluated in response to treatment with the synthetic endocannabinoid methanandamide. Selective agonists and antagonists were used to identify both the receptor and the biochemical pathways involved. SETTING: Molecular research institution. PATIENT(S): Endometrial tissues were obtained from 40 reproductive-age women undergoing laparoscopy for benign pathologies. INTERVENTIONS: ESCs were treated with methanadamide and with selective agonist (ACEA) and antagonist (AM251) of the cannabinoid receptor 1. MAIN OUTCOME MEASURES: Cellular migration was evaluated by means of chemotaxis experiments in a Boyden chamber. Electric signal generated by K(+) channels was evaluated by patch clamp experiments Cellular morphology and cytoskeletal-actin dynamics were evaluated by immunofluorescence. RESULT(S): Methanandamide enhanced ESC migration via cannabinoid receptor I (CNR1) through the activation of PI3K/Akt and ERK1/2 pathways. The increased ESC migration was associated with cytoskeleton reorganization identified by the dissolution of F-actin stress fibers and the presence of stress fiber arcs and with increased electrical signal generated by K(+) channels. CONCLUSION(S): In physiologic conditions, the cannabinoid system has a central role in regulating endometrial cell migration. The involvement of ERK1/2 and PI3-K/Akt pathways points to a potential role of endocannabinoids in some pathologic conditions characterized by enhanced endometrial cell invasiveness.
