Abstract
Microcystin-leucine arginine (MC-LR) is a harmful cyanotoxin produced by cyanobacteria. MC-LR can exert endocrine-disrupting activities in many organisms. We have previously demonstrated that MC-LR exerts both acute and chronic reproductive toxicity in male mice, resulting in a decline in sperm quality and damage to testicular structure. Moreover, we also observed extensive alterations in a panel of microRNAs in spermatogonial cells after exposure to MC-LR. In this study, we have confirmed that miR-541 was significantly increased both in GC-1 cells (in vitro) and in mouse testes (in vivo) after exposure to MC-LR. Our data support that p15 was the target gene of miR-541. Increase in miR-541 led to a reduction of p15 and murine double minute2 (MDM2), promoting the activation of p53 signaling and MC-LR-mediated cell apoptosis. Moreover, cells responded to MC-LR with reduced viability and increased apoptosis. Consistently, inhibiting miR-541 could upregulate the expression of p15 and MDM2, resulting in the downregulation of phospho-p53. Downregulation of miR-541 promoted cell viability by reducing MC-LR-induced cell apoptosis. In conclusion, we demonstrate here a crucial role for miR-541 in MC-LR-induced toxic effects on the reproductive system, in an attempt to provide a rational strategy for the diagnosis and treatment of MC-LR-induced impairment in the reproductive system.
Highlights
The presence of cyanobacteria in water bodies is common, and the development of cyanobacterial blooms has become more frequent and severe in the past decades [1,2,3,4,5]
We further investigated the effect of manipulated miR‐541 expression on the expression of p15 was not modulated by the regulation of miR-541, which was consistent with our protein levels of p15, murine double minute2 (MDM2), phospho‐MDM2, p53 and phospho‐p53 either with or without exposure in vitro data
Our previous work has that the low-dose, of endocrine disrupting chemicals previous work has confirmed that low‐dose, chronic chronic exposure to microcystin-leucine arginine (MC-LR)
Summary
The presence of cyanobacteria in water bodies is common, and the development of cyanobacterial blooms has become more frequent and severe in the past decades [1,2,3,4,5]. Microcystins (MCs) are a family of cyclic heptapeptide compounds produced by cyanobacterial species [6,7] and have been the subject of worldwide concern in recent decades [8]. Owing to their accumulation in aquatic creatures, MCs present health hazards to humans and animals higher up in the food chain [9]. More than 80 variants of MCs have been identified in freshwater systems [10], among which microcystin-leucine arginine (MC-LR) is the most common MC species [11].
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