Implications of dysregulated endogenous cannabinoid family members in the pathophysiology of endometriosis

Objective: To determine the involvement of the endocannabinoid (EC) family member in the pathophysiology of endometriosis (EMS).

Design: Mass spectrometry analysis of plasma and tissue samples from patients with EMS, controls, and a mouse model of EMS and messenger RNA and immunohistochemistry analysis of the samples from patients with EMS and controls.

Setting: Academic teaching hospital and university.

Patient(s): Patients with EMS and healthy fertile control subjects.

Intervention(s): None.

Main outcome measure(s): Endocannabinoid analysis in patient plasma, EMS lesions, and healthy endometrial samples.

Result(s): Circulating ECs were detected in the plasma samples, whereas no significant changes were observed in patients with EMS compared with healthy fertile controls. However, the palmitoylethanolamide levels were significantly higher in the EMS lesions than in the endometrium from patients with EMS. Similarly, genes involved in the EC signaling pathways were differentially expressed in the EMS lesions. Analysis of cannabinoid 1 and 2 receptors in the EMS lesions revealed a significantly lower cannabinoid 2 receptor expression, whereas no significant changes were observed in cannabinoid 1 receptor expression compared with those in the endometrium from both patients with EMS and healthy fertile controls. The palmitoylethanolamide levels were significantly elevated in plasma from EMS mice compared with that from sham controls and in EMS lesions compared with uterine samples.

Conclusion(s): Together, we provide evidence toward dysregulation of members of the ECs in both patients with EMS and the mouse model of EMS. These findings will advance the knowledge of the role of ECs in EMS and their potential implications as therapeutic targets.