O-073 Delta-9-THC acts on the calcium channel CatSper and alters human sperm function

Abstract

Study question Do the main psychoactive phytocannabinoid delta-9-tetrahydrocannabinol (THC) and its non-psychoactive analog cannabidiol (CBD) affect human sperm function? Summary answer THC reduces the ligand-dependent activation of sperm-specific Ca2+ channel CatSper and affects human sperm functions in vitro. What is known already Marijuana (Cannabis sativa) is one of the most commonly used recreational drugs worldwide. Although the impact of phytocannabinoids on reproductive health has been investigated, there is no evidence of a direct effect of THC on CatSper function. Study design, size, duration We studied the effects of the main psychoactive phytocannabinoid, THC, its non-psychoactive analog, CBD, as well as their major metabolites on Ca2+ influx via CatSper in human spermatozoa. THC and CBD were selected to further evaluate their action on progesterone-, prostaglandin-, and pH-induced activation of human CatSper. The effects of THC and CBD on hyperactivation, progressive motility in viscous media, and acrosomal exocytosis were also assessed. Participants/materials, setting, methods The impact of phytocannabinoids on CatSper activity was investigated on sperm samples from healthy volunteers using kinetic Ca2+ fluorimetry. Motility assessment was performed using Computer-Assisted Sperm Analysis (CASA). Sperm penetration into viscous media was assessed using a modified Kremer test. Acrosomal exocytosis was evaluated by flow cytometry using Pisum sativum agglutinin-stained spermatozoa. Main results and the role of chance Both THC and CBD suppress natural ligand-induced calcium influx via CatSper. In particular, THC inhibits progesterone-induced Ca2+ influx via CatSper at pharmacologically relevant concentrations in a non-competitive manner and reduces the pH-induced activation of CatSper. In addition, THC impaired sperm hyperactivation and penetration into viscous media and induced spontaneous acrosomal exocytosis in vitro. Limitations, reasons for caution This is an in vitro study. Future studies are needed to test the physiological relevance in vivo and whether THC can disrupt human sperm function. Wider implications of the findings The action of THC on CatSper in human sperm might impair the fertilization process. Healthcare providers, especially fertility clinicians, should be aware of the potentially negative effects of cannabis consumption on sperm physiology Trial registration number not applicable