Toxic Mechanisms of 3-Monochloropropane-1,2-Diol on Progesterone Production in R2C Rat Leydig Cells
Toxic Mechanisms of 3-Monochloropropane-1,2-Diol on Progesterone Production in R2C Rat Leydig Cells
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3-一氯丙烷-1,2-二醇对 R2C 大鼠间质细胞黄体酮产生的毒性机制。
DOI：
10.1021/jf400809r
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发表时间：
2013-10-16
影响因子：
6.1
通讯作者：
Huang, Yadong
中科院分区：
文献类型：
--
作者：
Sun, Jianxia;Bai, Shun;Huang, Yadong
3-一氯丙烷-1，2-二醇（3-MCPD）是一种众所周知的食品加工污染物，已被证明会阻碍男性生殖功能。然而，其作用机制仍有待阐明。在这项研究中，3-MCPD对孕酮生产的影响进行了研究，使用R2 C Leydig细胞。3-在IC 25、IC 50和IC 75水平分别为1.027、1.802和3.160 mM时，MCPD对细胞活力产生浓度依赖性抑制。单细胞凝胶/彗星实验和原子力显微镜实验显示3-MCPD可诱导早期细胞凋亡。此外，3-MCPD通过降低R2 C细胞中细胞色素P450侧链裂解酶、类固醇生成急性调节蛋白和3β-羟基类固醇脱氢酶的表达，显著降低孕酮的产生。类固醇生成急性调节蛋白表达的变化与孕酮的产生高度一致。线粒体膜电位和cAMP水平明显降低。
3-Monochloropropane-1,2-diol (3-MCPD) is a well-known food processing contaminant that has been shown to impede the male reproductive function. However, its mechanism of action remains to be elucidated. In this study, the effects of 3-MCPD on progesterone production were investigated using R2C Leydig cells. 3-MCPD caused concentration-dependent inhibition of cell viability at the IC25, IC50, and IC75 levels of 1.027, 1.802, and 3.160 mM, respectively. Single cell gel/comet assay and atomic force microscopy assay showed that 3-MCPD significantly induced early apoptosis. In addition, 3-MCPD significantly reduced progesterone production by reducing the expression of cytochrome P450 side-chain cleavage enzyme, steroidogenic acute regulatory protein, and 3β-hydroxysteroid dehydrogenase in R2C cells. The change in steroidogenic acute regulatory protein expression was highly consistent with progesterone production. Furthermore, the mitochondrial membrane potential and cAMP significantly decreased.