High Levels of Endocannabinoids in Human Follicular Fluid

Introduction: Endocannabinoids (eCBs) are internal lipid mediators that bind to cannabinoid receptors. The endocannabinoid system, consisting of eCBs, their receptors, and the enzymes involved in their biosynthesis and degradation, has been shown to play a role in reproduction and ovarian follicular activity in murine models.

Aim: To assess the presence of eCBs in human follicular fluid and embryos culture media.

Materials & Methods: Follicular fluid collected from 2 women undergoing ovum pick up in IVF after identification and separation of the oocyte. The embryos culture media were collected after transfer of the embryo to the uterus. Following a lipid extraction procedure, the levels of the following eCBs [Arachidonuc acid (AA), Anandamide (AEA), 2-arachidonoyl glycerol (2-AG), and Oleoylethanolamine (OEA)] were measured by liquid chromatography/tandem mass spectrometry (LC-MS/MS).

Results: In this preliminary study, we did not detect any of the four measured eCBs in the spent media collected from the embryo dishes after transferring of the embryos to the uterus. However, we could measures high levels of these eCBs in follicular fluids: AA – 1029.1 pmol/mL, AEA – 508.7 fmol/mL, 2-AG – 35.3 pmol/mL, and OEA – 5.2 pmol/mL. These levels are comparable to levels usually found in the blood and different organs.

Conclusions: These findings show that eCBs are present in the human ovarian follicles and might have an impact on ovarian functions. Further studies would need to confirm these results in a larger cohort of patients, and assess the contribution of the endocannabinoid system to folliculogenesis in health and disease.