title: The toxic effects of microcystin-LR on rat spermatogonia in vitro.
abstract: 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.
authors.affiliation: Medical School, Nanjing University, Nanjing, Jiangsu 210093, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Jintao
authors.initials: J
authors.lastname: Yuan
authors.forename: Jiang
authors.initials: J
authors.lastname: Wu
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Han
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D008297:Male; D008387:Marine Toxins; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D052998:Microcystins / Q000633:toxicity*; D008856:Microscopy, Fluorescence; D027361:Organic Anion Transporters / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013093:Spermatogonia / Q000187:drug effects* / Q000378:metabolism; D013737:Testis / Q000187:drug effects* / Q000378:metabolism
chemical_list: D008387:Marine Toxins; D052998:Microcystins; D027361:Organic Anion Transporters; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C057862:cyanoginosin LR