The fundamental role of the endocannabinoid system in endometrium and placenta: implications in pathophysiological aspects of uterine and pregnancy disorders
The endocannabinoid system (ECS) consists of cannabinoids produced naturally by the body – mainly anandamide (AEA) and 2-arachidonoylglycerol (2-AG), the cannabinoid receptors that they interact with – CB1 and CB2, and enzymes that synthesize and degrades them. In recent years, the importance of the ECS in both normal functions and diseases of the female reproductive system, including the endometrium and the placenta, has come into focus, owing to both laboratory research and clinical observations.
In particular, the level of AEA was found to increase significantly in the blood of patients with endometriosis and miscarriage, in the fallopian tube of women with ectopic pregnancy and in endometrial biopsies of endometrial tumor. Moreover, the expression pattern of the cannabinoid receptor CB1 was demonstrated to be abnormal in endometrial biopsies of endometriosis, in fallopian tube and decidua of patients with ectopic pregnancy, and in preeclamptic placenta. Finally, alterations in CB2 expression patterns in endometrial tissues have been reported to be associated with endometrial cancer.
In short, abnormalities in the ECS have been consistently linked to common female reproductive disorders including endometriosis, ectopic pregnancy, miscarriage, pre-eclampsia and endometrial cancer. For this reason, drugs that target the ECS may serve as promising new therapies for patients suffering from these diseases.