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.

诸如四氢大麻酚（THC）的外源大麻素可能会改变内源大麻素在男性生殖中的生理功能，从而影响男性的生育能力。本研究旨在通过与p53和AKT信号通路相关的机制研究THC对Sertoli细胞和生精生殖细胞的凋亡作用，以及硒预处理在体内和体外模型中的可能的保护作用。该小家鼠Sertoli细胞系TM4用于体外实验。培养TM4细胞，并使其暴露于硒（2μM，48 h）和四氢大麻酚（470μM，24 h）中。进行MTT测试以评估细胞活力。将15只Wistar大鼠（220±20 g）用于体内实验，分为三组：（1）对照，（2）四氢大麻酚（THC，5 mg / kg，溶于5％DMSO的ip，连续21次）天），以及（3）THC +硒（硒，每天0.5 mg / kg，腹腔注射）。在实验结束时，收集了支持细胞和睾丸组织样本用于生化（AKT，P53），细胞凋亡和组织学分析。体外研究的结果表明，四氢大麻酚显着降低了细胞活力（p <0.001）和p-AKt蛋白的表达（p<0.05）并增加Sertoli细胞的凋亡（p <0.001）和p53蛋白表达（p <0.001）。THC的体内作用与体外结果一致。硒（作为亚硒酸钠）预处理可显着降低THC诱导的大鼠支持细胞和睾丸组织损伤。硒预处理的大鼠的病理学改变明显减轻。总的来说，这些数据表明用硒预处理能够预防THC诱导的睾丸细胞损伤。硒的衰减作用可能是由于其通过p53和AKT调节的抗凋亡活性所致。