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Toxins 2016, 8(9), 260; doi:10.3390/toxins8090260

miR-541 Contributes to Microcystin-LR-Induced Reproductive Toxicity through Regulating the Expression of p15 in Mice

1,2,* and 1,2,*
Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, 22 Hankou Road, Nanjing 210093, Jiangsu, China
Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, 22 Hankou Road, Nanjing 210093, Jiangsu, China
Department of Health Technology and Informatics, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China
Authors to whom correspondence should be addressed.
Academic Editors: Lesley V. D’Anglada, Elizabeth D. Hilborn and Lorraine C. Backer
Received: 19 June 2016 / Accepted: 31 August 2016 / Published: 6 September 2016
(This article belongs to the Collection Freshwater HABs and Health in a Changing World)
View Full-Text   |   Download PDF [8372 KB, uploaded 6 September 2016]   |  


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. View Full-Text
Keywords: MC-LR; miR-541; p15; male reproduction; apoptosis MC-LR; miR-541; p15; male reproduction; apoptosis

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Meng, X.; Zhang, L.; Chen, X.; Xiang, Z.; Li, D.; Han, X. miR-541 Contributes to Microcystin-LR-Induced Reproductive Toxicity through Regulating the Expression of p15 in Mice. Toxins 2016, 8, 260.

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