The role of cannabinoid agonists and antagonists on folliculogenesis and evolutionary events in the mouse ovary

Objective(s): Cannabinoids, derivatives of Cannabis sativa L., can activate the endocannabinoid system via two endogenous receptors, CB۱ and CB۲. This system is crucial in regulating folliculogenesis, fertility, and reproductive function. This study investigated the potential effects of cannabinoid agonists and antagonists on ovarian health and function in female mice.Materials and Methods: ۸۰ NMRI mice were divided into ۱۰ groups. Treatment groups received CB۱ or CB۲ agonists, antagonists, or their combinations for five days. The animals were then sacrificed, the ovaries were excised and weighed, and their volume was measured. Total RNA was extracted from the left ovary for qPCR analysis, while the right ovary was fixed in Bouin’s solution for histological evaluation following H&E staining.Results: Treatment with CB۱/CB۲ agonist+CB۱ antagonist (W۱۰۲+AM۲۵۱) decreased the level of NAPE-PLD (a key factor in the production of endocannabinoids in cells) and increased the level of FAAH (responsible for cannabinoid degradation) genes compared to all groups. CB۲ antagonist (AM۶۳۰) increased the number of primary, preantral, and antral follicles, the volume and weight of ovaries, and estrogen levels. Meanwhile, the CB۱ antagonist (AM۲۵۱) significantly increased microvascular density in the ovaries.Conclusion: Cannabinoids modulate ovarian physiology and folliculogenesis, with CB۲ receptors playing a particularly significant role. Antagonism at CB۲ appeared to differentially affect cannabinoid-metabolizing enzymes in ovarian follicles and differentially affect their maturation. However, our preliminary novel findings in mice require human studies before clinical application.

کلیدواژه ها:

Cannabinoid ، Cannabinoid agonist ، Cannabinoid antagonist ، Cb۱ receptor ، CB۲ receptor ، Folliculogenesis