期刊
TOXICOLOGY
卷 326, 期 -, 页码 1-8出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2014.09.009
关键词
Nonylphenol isomer; Cell receptor; Mitogen-activated protein kinase; TM4 cell
资金
- National Basic Research Program of China (973 program) [2012CB720805]
- International Science & Technology Cooperation Program of China [2010DFA31780]
- Joint Sino-German Research Project of National Natural Science Foundation of China [GZ 731]
- Program for New Century Excellent Talents in University [NCET-12-0749]
In the present study, experiments were performed to investigate the effects of nonylphenol (NP) isomers (4-[1,2, 4-trimethylhexyl]-phenol (NP41), 4-[1,2, 5-trimethylhexyl]-phenol (NP42)) on Sertoli TM4 cells. NP41 decreased mRNA expression levels of androgen receptor and toll-like receptor (TLR)-4 in 20-40 mu M (P<0.05), and increased mRNA levels of estrogen receptor (ER)-alpha and progesterone receptor in 1-40 mu M (P<0.05). NP42 treatment only evoked significant decrease in mRNA expression levels of ER-alpha in 20-40 mu M (P<0.05). Similarly, NP41 (1-40 mu M) drastically increased the protein expression of ER-alpha, which was significantly decreased in 20-40 mu M NP42 groups (P<0.01). Both NP41 and NP42 showed no effect on the expression of ER-beta. Protein levels of follicle stimulating hormone receptor were increased significantly in high concentrations of NP41 (40 mu M) and NP42 (10-40 mu M) challenged cells. Furthermore, NP41 and NP42 showed various effects on the expression of junction-associated molecules and inhibin B secretion in TM4 cells. Additionally, activation of JNK1/2 pathway was induced by NP41 and NP42. However, ERK1/2 and p38 pathways were inhibited in TM4 cells exposed to low concentrations of NP41 (0.1-20 mu M) and NP42 (0.1-1 mu M), and high concentrations of NP41 (40 mu M) and NP42 10-40 mu M) resulted in a return of p-ERK1/2 and p-p38 to control levels. We proposed that molecular mechanism of reproductive damage in Sertoli cells induced by NPs may be mediated by cell receptors and/or cell signaling pathways, and the effects may be related to the structure of NP isomer. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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