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Published in: Reproductive Biology and Endocrinology 1/2011

Open Access 01-12-2011 | Research

miRNA regulation of cytotoxic effects in mouse Sertoli cells exposed to nonylphenol

Authors: Jin-Sung Choi, Jung-Hwa Oh, Han-Jin Park, Mi-Sun Choi, Se-Myo Park, Seung-Jun Kang, Moon-Ju Oh, Seung Jun Kim, Seung Yong Hwang, Seokjoo Yoon

Published in: Reproductive Biology and Endocrinology | Issue 1/2011

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Abstract

Background

It is known that some environmental chemicals affect the human endocrine system. The harmful effects of endocrine disrupting chemical (EDC) nonylphenol (NP) have been studied since the 1980s. It is known that NP adversely affects physiological functions by mimicking the natural hormone 17 beta-estradiol. In the present study, we analyzed the expression of miRNAs and their target genes in mouse Sertoli TM4 cells to better understand the regulatory roles of miRNAs on Sertoli cells after NP exposure.

Methods

Mouse TM4 Sertoli cells were treated with NP for 3 or 24 h, and global gene and miRNA expression were analyzed using Agilent mouse whole genome and mouse miRNA v13 arrays.

Results

We identified genes that were > 2-fold differentially expressed in NP-treated cells and control cells (P < 0.05) and analyzed their functions through Gene Ontology analysis. We also identified miRNAs that were differentially expressed in NP-treated and control cells. Of the 186 miRNAs the expression of which differed between NP-treated and control cells, 59 and 147 miRNAs exhibited 1.3-fold increased or decreased expression at 3 and 24 h, respectively. Network analysis of deregulated miRNAs suggested that Ppara may regulate the expression of certain miRNAs, including miR-378, miR-125a-3p miR-20a, miR-203, and miR-101a, after exposure to NP. Additionally, comprehensive analysis of predicted target genes for miRNAs showed that the expression of genes with roles in cell proliferation, the cell cycle, and cell death were regulated by miRNA in NP-treated TM4 cells. Levels of expression of the miRNAs miR-135a* and miR-199a-5p were validated by qRT-PCR. Finally, miR-135a* target gene analysis suggests that the generation of reactive oxygen species (ROS) following exposure to NP exposure may be mediated by miR-135a* through regulation of the Wnt/beta-catenin signaling pathway.

Conclusions

Collectively, these data help to determine NP's actions on mouse TM4 Sertoli cells and increase our understanding of the molecular mechanisms underlying the adverse effects of xenoestrogens on the reproductive system.
Appendix
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Metadata
Title
miRNA regulation of cytotoxic effects in mouse Sertoli cells exposed to nonylphenol
Authors
Jin-Sung Choi
Jung-Hwa Oh
Han-Jin Park
Mi-Sun Choi
Se-Myo Park
Seung-Jun Kang
Moon-Ju Oh
Seung Jun Kim
Seung Yong Hwang
Seokjoo Yoon
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2011
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/1477-7827-9-126

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