Author:
Govahi Azam,Eghbali Sahar,Ajdary Marziyeh,Amjadi Fatemehsadat,Nazari Mahsa,Kazorgah Farzaneh Mohammadzadeh,Mehdizadeh Mehdi
Abstract
Abstract
Background
Considering the growing therapeutic use of cannabidiol as well as the presence of cannabinoid receptors in sperm and its possible genotoxic activity, the effect of cannabidiol on sperm quality and function was examined.
Methods
Thirty male NMRI mice were randomly divided into three groups: control (no injection), sham (intraperitoneal (IP) injection of DMSO daily for 34 days), and cannabidiol (IP injection of cannabidiol 30 mg/ml daily for 34 days). Following 35 days after the last injection, sperm parameters, chromatin integrity (CMA3 staining), acrosome reaction (FITC-PNA method), fertility-related genes (IZUMO1, PLCζ), and blastulation rate of the embryos obtained from the oocytes fertilized with the mentioned sperms was investigated.
Results
Count, motility, and morphology of sperm were not significantly affected by cannabidiol. CMA3+ sperms (protamine deficiency) were significantly higher in the cannabidiol group compared to the control group (P = 0.03). The acrosomal reaction and fertility-related genes (IZUMO1, PLCζ) in the cannabidiol group did not differ significantly compared to the control group. Also, there was no significant difference between the cannabidiol group and the control group in the two-cell and the eight-cell stages but the rate of blastocyst formation was significantly lower in the cannabidiol group compared to other groups (P < 0.0001).
Conclusions
Our results showed that cannabidiol leads to negative effects on the male reproductive system through an effect on sperm chromatin and the rate of reaching the blastocyst stage of the embryo.
Graphical Abstract
Publisher
Springer Science and Business Media LLC
Reference52 articles.
1. Di Giacomo D, De Domenico E, Sette C, Geremia R, Grimaldi P (2016) Type 2 cannabinoid receptor contributes to the physiological regulation of spermatogenesis. Faseb j. 30(4):1453–63. https://doi.org/10.1096/fj.15-279034
2. Gonsiorek W, Lunn C, Fan X, Narula S, Lundell D, Hipkin RW (2000) Endocannabinoid 2-arachidonyl glycerol is a full agonist through human type 2 cannabinoid receptor: antagonism by anandamide. Mol Pharmacol. 57(5):1045–50
3. Agirregoitia E, Carracedo A, Subirán N, Valdivia A, Agirregoitia N, Peralta L et al (2010) The CB(2) cannabinoid receptor regulates human sperm cell motility. Fertil Steril. 93(5):1378–87. https://doi.org/10.1016/j.fertnstert.2009.01.153
4. Atalay S, Jarocka-Karpowicz I, Skrzydlewska E (2019) Antioxidative and anti-inflammatory properties of cannabidiol. Antioxidants. 9(1):21
5. Wanner NM, Colwell M, Drown C, Faulk C (2020) Subacute cannabidiol alters genome-wide DNA methylation in adult mouse hippocampus. Environ Mol Mutagen. 61(9):890–900