Background: Cannabinoids, as member of Cannabis sativa L. derivatives (such as marijuana, hashish) are able to activate the endocannabinoid system via two endogenous receptors CB1 and CB2. This system plays an important role in the regulating folliculogenesis and fertility and affects many of the processes of the reproductive system. This study was conducted to investigate the possible effects of cannabinoid agonists and antagonists on the ovarian health and function of female mice.
Material & Method: A total of 80 NMRI mice were divided into 10 groups. Treatment groups received CB1 or CB2 agonist or antagonist or a combination of them for 5 days. Animals were sacrificed;ovaries were removed, measured to determine the weight and volume, total RNA from the left ovary was extracted for q-PCR, and the right ovary was fixed in Boin’s fixative to evaluate folliculogenesis.
Results:Treatment of animals with CB1/CB2 agonist + CB1 antagonist (W102+AM251) decreased the level of NAPE-PLD and increased the level of FAAH gene compared to all groups. CB2 antagonist (AM630) increased the number of primary, preantral and antral follicles as well as the volume and weight of ovaries, and estrogen levels. While the CB1 antagonist (AM251) significantly increased the number of micro vessels in the ovary.
Conclusion: Cannabinoid products affect the physiology of the ovaries and impair folliculogenesis. The CB2 receptor appears to play a major role in this process. Antagonism at CB2 appeared to differentially affect cannabinoid-metabolizing enzymes in ovarian follicles and also differentially affects their maturation.. However, our preliminary novel findings in mice require human studies before application in clinics