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Title: miR-541 contributes to microcystin-LR-induced reproductive toxicity through regulating the expression of p15 in mice
Authors: Meng, X
Zhang, L
Chen, X
Zou, X 
Li, D
Han, X
Keywords: Apoptosis
Male reproduction
Issue Date: 2016
Publisher: Molecular Diversity Preservation International (MDPI)
Source: Toxins, 2016, v. 8, no. 9, 260, p.1-16 How to cite?
Journal: Toxins 
Abstract: Microcystin-leucine arginine (MC-LR) is a harmful cyanotoxin produced by cyanobacteria. MC-LR can exert endocrine-disrupting activities inmany 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.
ISSN: 2072-6651
DOI: 10.3390/toxins8090260
Rights: © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (
The following publication Meng, X., Zhang, L., Chen, X., Xiang, Z., Li, D., & Han, X. (2016). miR-541 contributes to Microcystin-LR-induced reproductive toxicity through regulating the expression of p15 in mice. Toxins, 8(9), 260 is available at
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