Abstract
Microcystins (MCs), the secondary metabolites of blue-green algae, are ubiquitous and major cyanotoxin contaminants. Besides the hepatopancreas/liver, the reproductive system is regarded as the most important target organ for MCs. Although reactive oxygen species (ROS) have been implicated in MCs-induced reproductive toxicity, the role of MCs in this pathway remains unclear. In the present study, Sertoli cells were employed to investigate apoptotic death involved in male reproductive toxicity of microcystin-LR (MC-LR). After exposure to various concentrations of MC-LR for 24 h, the growth of Sertoli cells was concentration-dependently decreased with an IC50 of ~32 μg/mL. Mitochondria-mediated apoptotic changes were observed in Sertoli cells exposed to 8, 16, and 32 μg/mL MC-LR including the increased expression of caspase pathway proteins, collapse of mitochondrial membrane potential (MMP), and generation of ROS. Pretreatment with a global caspase inhibitor was found to depress the activation of caspases, and eventually increased the survival rate of Sertoli cells, implying that the mitochondrial caspases pathway is involved in MC-LR-induced apoptosis. Furthermore, N-acetyl-l-cysteine attenuated the MC-LR-induced intracellular ROS generation, MMP collapse and cytochrome c release, resulting in the inhibition of apoptosis. Taken together, the observed results suggested that MC-LR induced apoptotic death of Sertoli cells by the activation of mitochondrial caspases cascade, while its effects on the ROS-mediated signaling pathway may contribute toward the initiation of mitochondrial dysfunction.
Highlights
In recent years, eutrophication caused by cyanobacteria bloom events occurs frequently in the global scope
Our recent study addressing acute low-dose exposure to MC-LR demonstrated its ability to induce oxidative damage in vitro; MC-LR decreased cell viability, reduced mitochondrial membrane potential (MMP), up-regulated antioxidant activity, and increased the production of reactive oxygen species (ROS) and lipid peroxidation (Xue et al, 2015). These results suggested that ROS might constitute a direct cause of mitochondrial dysfunction, it remains controversial as to how ROS functions during MC-LR-mediated Sertoli cells apoptosis
The present data demonstrated that ROS generation is the primary effect caused by MC-LR-induced apoptosis in rat sertoli cells, with subsequent MMP collapse, Cyt c release, eventually leading to the involvement of other mitochondria-mediated pathways at indicated dosages
Summary
Eutrophication caused by cyanobacteria bloom events occurs frequently in the global scope. Microcystins (MCs) are the most extensively studied owing to their ubiquity and high toxicity (Campos and Vasconcelos, 2010; Puddick et al, 2014). A large number of studies have confirmed that liver is the first target organ for MC-LR with resultant hepatotoxicity (Sun et al, 2011; Li and Han, 2012; Chen et al, 2013; Wang et al, 2014; Li et al, 2015). Gonads are the second most important target organs for MCs (Chen and Xie, 2005), and recent studies have indicated that MCs can be accumulated in male gonads of rodents, and exert adverse reproductive effects in a dose- and time-dependent manner The impaired Sertoli cells would be harmful to male reproduction
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