Medical School, Nanjing University, Nanjing, Jiangsu 210093, PR China.
Toxicol Lett. 2012 Jul 7;212(1):48-56. doi: 10.1016/j.toxlet.2012.05.001. Epub 2012 May 10.
Microcystin-leucine arginine (MC-LR), a cyclic heptapeptide produced by several bloom-forming cyanobacteria, has strong reproductive toxicity. We examined whether MC-LR could enter spermatogonia and investigated the toxic effects of MC-LR on spermatogonia in vitro. Multispecific organic anion-transporting polypeptides (Oatps), which transported MCs, were screened as well. Spermatogonia were exposed to 0, 0.5, 5, 50, and 500 nmol/L (nM) MC-LR for 6 h. Cell viability and total antioxidant capacity significantly decreased, meanwhile, the ratio of apoptotic cells, reactive oxidative species (ROS) production, mitochondrial membrane potential (MMP), and intracellular free Ca²⁺ increased after exposure to 5 nM and higher concentrations of MC-LR. MC-LR can immigrate into spermatogonia. At least 5 Oatps (Oatp1a5, -3a1, -6b1, -6c1, and -6d1) were detected at the mRNA level in spermatogonia, and the expression of these Oatps was affected by MC-LR, especially Oatp3a1. This study demonstrated that MC-LR can be transported into spermatogonia and leads to cytotoxicity.
微囊藻氨酸-亮氨酸-精氨酸（MC-LR）是由几种蓝藻水华产生的一种环状七肽，具有很强的生殖毒性。我们研究了 MC-LR 是否可以进入精原细胞，并在体外研究了 MC-LR 对精原细胞的毒性作用。还筛选了多特异性有机阴离子转运多肽（Oatp），它们可以转运 MC。精原细胞暴露于 0、0.5、5、50 和 500 nmol/L（nM）MC-LR 6 小时。细胞活力和总抗氧化能力显著下降，而在暴露于 5 nM 及更高浓度的 MC-LR 后，凋亡细胞的比例、活性氧（ROS）产生、线粒体膜电位（MMP）和细胞内游离 Ca²⁺增加。MC-LR 可以进入精原细胞。至少有 5 种 Oatp（Oatp1a5、-3a1、-6b1、-6c1 和 -6d1）在精原细胞中以 mRNA 水平检测到，这些 Oatp 的表达受到 MC-LR 的影响，尤其是 Oatp3a1。这项研究表明，MC-LR 可以进入精原细胞并导致细胞毒性。
