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Exocannabinoids such as tetrahydrocannabinol (THC) may alter the physiological function of endocannabinoids in male reproduction and thus affect male fertility. This study aimed to investigate the apoptotic effects of THC via mechanisms related to p53 and AKT signaling pathways on Sertoli cells and seminiferous germinal cells, as well as the possible protective role of selenium pretreatment in both in vitro and in vivo models. The Mus musculus Sertoli cell line, TM4, was used for in vitro experiments. The TM4 cells were cultured and exposed to selenium (2 μM, 48 h) and THC (470 μM, 24 h). The MTT test was performed to evaluate cell viability. Fifteen male Wistar rats (220 ± 20 g) were used for in vivo experiments and divided into three groups: (1) control, (2) tetrahydrocannabinol (THC, 5 mg/kg, dissolved in DMSO 5%, i.p., for 21 consecutive days), and (3) THC + selenium (selenium, 0.5 mg/kg per day, i.p.). At the end of the experiments, Sertoli cells and testis tissue samples were collected for biochemical (AKT, P53), cell apoptosis, and histological analyses. The results of the in vitro study revealed that THC significantly decreases the cell viability (p < 0.001) and expression of the p-AKt protein (p < 0.05) and increases Sertoli cells' apoptosis (p < 0.001) and p53 protein expression (p < 0.001). The in vivo effects of THC were in line with the in vitro results. Pretreatment with selenium (as sodium selenite) significantly decreased the THC-induced Sertoli cell and testicular tissue damages in the rats. Pathological changes were significantly alleviated in the selenium-pretreated rats. Collectively, these data suggest that pretreatment with selenium is able to protect against THC-induced testicular cell damage. The attenuating effect of selenium may be due to its anti-apoptotic activity through the p53 and AKT modulation.
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.
Method:
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.
objective:
Background: Global rise in marijuana 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 marijuana. It has been reported that THC affects male fertility and causes testicular cells dysfunction and apoptosis.
Result:
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 anti-apoptotic and antioxidant activities, indicating its clinical importance against THC-induced testicular toxicity among addicted men.
conclusion:
The present data suggests that THC induces Sertoli cell damage through a multitarget mechanism. Zinc is able to protect against THC-induced Sertoli cell damages due to its anti-apoptotic and antioxidant activities and indicates the clinical importance of zinc against THC-induced testicular toxicity among addicted men.
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