Effect of Cannabidiol (CBD) on the fertility of sexually immature- treated mice

Shir Haim ^1,2 Eitan Lunenfeld ^2,3 Bara'ah Khaleel ^1,2 Eden Arazi ^1,2 Shimon Ben-Shabat ⁴ Pesach Shvartzman ⁵ Mahmoud Huleihel ^1,2

¹The Shraga Segal Department of Microbiology, Immunology and Genetics, Ben-Gurion University of the Negev, Israel
²The Center of Advanced Research and Education in Reproduction, Ben-Gurion University of the Negev, Israel
³Adelson Faculty of Medicine, Ariel University, Israel
⁴Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, Israel
⁵The Department of the Family Medicine, Ben-Gurion University of the Negev, Israel

Introduction: CBD is a phytocannabinoid constituent with broad therapeutic properties, including pain relief, seizures related to epilepsy in children, nausea and vomiting. Few studies showed that cannabis affected sperm parameters in adult humans, monkeys, and rodents.

Aims: To examine the effect of CBD on fertility parameters at puberty, of immature-treated mice.

Methodology: One-week-old male mice were intraperitoneally injected with CBD (10mg/Kg) [n= 7-15] or its solvent (CT; n= 5-10) daily for two weeks, or untreated (UT; n=6-7). Mice were sacrificed at 6-, 8-, 10-, and 12-week-old, and examined for testes and body weight, testicular histology, sperm parameters, and fertility.

Results: Normal histology of seminiferous tubules (STs) of CBD-treated mice significantly decreased (33%-15%; from 6-12 weeks, respectively) compared to untreated. Also, a significant reduction (22%-12%; from 6-12 weeks, respectively) was measured in the normal histology of STs of the CT compared to untreated. Sperm concentration significantly decreased in the CBD (40.54%) compared to UT only at 12w. However, the CT showed a significant reduction (57.69%) compared also to UT only at 8 weeks. CBD and UT had similar sperm motility at all ages, but CT showed a significant reduction (25%-13%) only from 6-10 weeks, respectively. The CT and CBD groups showed normal fertility and litter size at 10-12 weeks.

Conclusions: Based on our preliminary findings, STs histology and sperm parameters were reduced without affecting fertility. It is possible to suggest that even though CBD or its solvent showed negative effects, it did not affect male fertility at advanced ages.