The toxic effects of microcystin-LR on rat spermatogonia in vitro.

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.