ABSTRACT
BACKGROUND: Global rise in cannabis abuse during reproductive years has placed a large number of men at risk for the adverse consequences of δ-9-tetrahydrocannabinol (THC), the primary active component of cannabis. It has been reported that THC affects male fertility and causes testicular cell dysfunction and apoptosis. This study aimed to investigate the possible protective role of zinc pretreatment against the toxic effects of THC in cultured mouse Sertoli cells and the underlying mechanism. METHODS: The Mus Musculus Sertoli cell line (TM4) was cultured, exposed to THC alone (470 µM, 24 h), co-administered with zinc (8 µM, 48 h), and investigated in three groups: control, THC, and THC + zinc. The MTT was performed to evaluate cell viability. TUNEL assay was also applied for the detection of cell apoptosis and a western blot was performed for measuring protein expression levels of Caspase3, Pro-caspase3, SOD, and PDGF-A. RESULTS: THC significantly decreased cell viability (p < 0.001) and expression levels of SOD, PDGF-A, and pro-caspase3 proteins (p < 0.05 for all), whereas increased Sertoli cells apoptosis (p < 0.001) and expression level of cleaved caspase3 protein (p < 0.001). Pretreatment with zinc reversed THC-induced apoptotic and oxidative effects and reduced cleaved caspase3/pro-caspase3 ratio but could not reverse THC-induced reduction of PDGF-A expression level in TM4 cells. CONCLUSION: The present data suggest that THC induces Sertoli cell damage through a multitarget mechanism. Zinc was reported to protect against THC-induced Sertoli cell damage due to its antiapoptotic and antioxidant activities, indicating its clinical importance against THC-induced testicular toxicity among addicted men.
ABSTRACT
Background and aim: Alongside the advancement of various modern treatments, attention has recently been focused on finding alternative infertility treatments based on diet and herbal medicine. Pistacia atlantica (wild pistachio; Baneh) is a plant species traditionally known as a libido booster and sexual enhancer. Experimental procedure: The study aim was to evaluate the effects of a P. atlantica-enriched diet on the functions of the reproductive system of male rats. Results and conclusion: Results revealed that the diet containing 20% P. atlantica doubled testosterone levels in the treatment group compared to the control. It decreased the total bodyweight, while significantly increased the ratios of the seminal vesicles, testis, and epididymis to the bodyweight of rats. The sperm count in the treatment group was 4.8 × 106/mL, which was significantly more than the control group (4.2 × 106/mL). Furthermore, the utilization of P. atlantica significantly raised HDL levels, though it reduced the LDL and TG levels and the concentration of testis MDA. Concerning other factors, the 20% of P. atlantica considerably increased the serum level of Zinc and vitamin D. Histomorphometric analysis revealed that the diet increased the testicular capsule thickness, whereas it did not cause any significant change in the diameter of the seminiferous tubule, the number of Leydig cells, and Sertoli cells. Additionally, the repopulation index, tubular differentiation index, and spermiogenesis index increased in the treatment group. Molecular analysis showed that the prescribed diet increased the expression of both oxytocin (OXT) and its receptor (OXTR) genes, improving the reproductive system function.
