Li Mingwei, Sun Jianxia, Zou Feiyan, Bai Shun, Jiang Xinwei, Jiao Rui, Ou Shiyi, Zhang Hui, Su Zhijian, Huang Yadong, Bai Weibin
Department of Food Science and Engineering, Department of Developmental and Regenerative Biology, Biopharmaceutical R&D Center, Jinan University, Guangzhou, 510632, China.
Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, China.
Food Chem Toxicol. 2017 Oct;108(Pt B):563-570. doi: 10.1016/j.fct.2016.09.035. Epub 2016 Oct 28.
The food contaminant acrylamide (AA) is usually recognized as a probable human carcinogen. In addition, AA has also been found able to induce male infertility in animals. Interestingly, resent research work revealed that the toxic effect of AA on the ability of male reproduction in vivo may due to glycidamide (GA) which is the metabolite of AA. In this study, R2C Leydig cells was used to investigate the toxic effects of GA on progesterone production. GA caused dose-dependent inhibition on the cell growth, with IC, IC and IC values found at 0.635, 0.872, and 1.198 mM, respectively. The results of single cell gel/Comet assay showed that GA significantly induced early-phase cell apoptosis, reduced progesterone production, as well as decreasing the protein expression of steroidogenic acute regulatory (StAR) in R2C cells. Furthermore, GA induced overproduction of intracellular reactive oxygen species (ROS), upregulated Bax expression, decreased mitochondrial membrane potential, and triggered mitochondria-mediated cell apoptosis. Consequently, the downstream effector caspase-3 was activated, resulting in Leydig cells apoptosis. Overall, our results showed that GA could damage R2C Leydig cells by the lesion of the ability of progesterone genesis and inducing cells apoptosis.
食品污染物丙烯酰胺（AA）通常被认为是一种可能的人类致癌物。此外，还发现AA能够诱导动物雄性不育。有趣的是，最近的研究工作表明，AA在体内对雄性生殖能力的毒性作用可能归因于其代谢产物环氧丙酰胺（GA）。在本研究中，使用R2C Leydig细胞来研究GA对孕酮生成的毒性作用。GA对细胞生长产生剂量依赖性抑制，IC50、IC25和IC10值分别为0.635、0.872和1.198 mM。单细胞凝胶/彗星试验结果表明，GA显著诱导早期细胞凋亡，降低孕酮生成，并降低R2C细胞中类固醇生成急性调节蛋白（StAR）的蛋白表达。此外，GA诱导细胞内活性氧（ROS）过量产生，上调Bax表达，降低线粒体膜电位，并引发线粒体介导的细胞凋亡。因此，下游效应因子caspase-3被激活，导致Leydig细胞凋亡。总体而言，我们的结果表明，GA可通过损害孕酮生成能力和诱导细胞凋亡来损伤R2C Leydig细胞。
