title: Effects of 4-nonylphenol isomers on cell receptors and mitogen-activated protein kinase pathway in mouse Sertoli TM4 cells.
abstract: 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 20-40μM (P<0.05), and increased mRNA levels of estrogen receptor (ER)-α and progesterone receptor in 1-40μM (P<0.05). NP42 treatment only evoked significant decrease in mRNA expression levels of ER-α in 20-40μM (P<0.05). Similarly, NP41 (1-40μM) drastically increased the protein expression of ER-α, which was significantly decreased in 20-40μM NP42 groups (P<0.01). Both NP41 and NP42 showed no effect on the expression of ER-β. Protein levels of follicle stimulating hormone receptor were increased significantly in high concentrations of NP41 (40μM) and NP42 (10-40μM) 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 (0.1-20μM) and NP42 (0.1-1μM), and high concentrations of NP41 (40μM) and NP42 (10-40μM) 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.
authors.affiliation: State Key Laboratory of Food Science and Technology, Nanchang University, 235 Nanjing East Road, Nanchang 330047, China.
authors.forename: Xiaozhen
authors.initials: X
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Food Science and Technology, Nanchang University, 235 Nanjing East Road, Nanchang 330047, China.
authors.forename: Shaoping
authors.initials: S
authors.lastname: Nie
authors.affiliation: State Key Laboratory of Food Science and Technology, Nanchang University, 235 Nanjing East Road, Nanchang 330047, China.
authors.forename: Yangjie
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Food Science and Technology, Nanchang University, 235 Nanjing East Road, Nanchang 330047, China.
authors.forename: Danfei
authors.initials: D
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Food Science and Technology, Nanchang University, 235 Nanjing East Road, Nanchang 330047, China. Electronic address: myxie@ncu.edu.cn.
authors.forename: Mingyong
authors.initials: M
authors.lastname: Xie
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D007265:Inhibins / Q000378:metabolism; D007365:Intercellular Junctions / Q000187:drug effects / Q000378:metabolism; D007536:Isomerism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010636:Phenols / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012708:Sertoli Cells / Q000187:drug effects* / Q000201:enzymology
chemical_list: D010636:Phenols; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C422364:inhibin B; D007265:Inhibins; D020928:Mitogen-Activated Protein Kinases; C041594:4-nonylphenol
keywords: Cell receptor; Mitogen-activated protein kinase; Nonylphenol isomer; TM4 cell