Post-weaning exposure to cannabidiol disrupts testicular cytoarchitecture and sperm quality in mice

Abstract

Cannabidiol (CBD) is a natural cannabinoid with a wide range of potential therapeutic applications, including as an anticonvulsant and for the treatment of inflammatory conditions. It is known that CBD interacts with the endocannabinoid system, which plays a crucial role in various physiological functions. However, its effects on male reproduction have not yet been fully elucidated. Thus, the aim of this study was to evaluate the in vivo effects of CBD on testicular cytoarchitecture and sperm quality in mice. Twenty-one-day old male Swiss mice received intragastric doses of CBD (15 or 30 mg/kg/day) for 34 consecutive days. A control group received sunflower oil. Both doses of CBD reduced the number of Sertoli cells at stages VII–VIII, IX and XII of spermatogenesis. A significant decrease in proliferating cell nuclear antigen (PCNA)-positive spermatocytes at stages VII–VIII was observed in the CBD15 group. In the interstitial compartment of the testis, no significant differences were found in the diameter and volume of Leydig cell nuclei or in the immunostaining of these cells for PCNA in the control and CBD-treated groups. Both doses of CBD reduced the percentage of viable spermatozoa and the percentage of morphologically normal spermatozoa. These findings suggest that daily exposure to CBD may reduce sperm quality, and the mechanisms responsible may be related to perturbations in the endocannabinoid system during spermatogenesis.