title: Downregulation of steroid hormone receptor expression and activation of cell signal transduction pathways induced by a chiral nonylphenol isomer in mouse sertoli TM4 cells.
abstract: Nonylphenols (NPs) are considered as important environmental toxicants and potential endocrine disrupting compounds which can disrupt male reproductive system. 4-[1-Ethyl-1-methylhexy] phenol (4-NP65) is one of the main isomers of technical nonylphenol mixtures. In the present study, effect of NPs was evaluated from an isomer-specific viewpoint using 4-NP65. Decreased mRNA expression levels of estrogen receptor (ER)-α, ER-β, androgen receptor (AR) and progesterone receptor (PR) were observed in the cells exposed to 4-NP65for 24 h. Furthermore, 4-NP65treatment evoked significant decrease in protein expression levels of ER-α and ER-β. Levels of mullerian inhibiting substance and transferrin were found to change significantly in 4-NP65challenged cells. Additionally, JNK1/2-MAPK pathway was activated due to 4-NP65exposure, but not ERK1/2 and p38-MAPK pathways. Meanwhile, 4-NP65increased the p-Akt level and showed no effects on the Akt level which indicated that Akt pathway was activated by 4-NP65. In conclusion, these findings have shown that 4-NP65exposure affected expression of cell receptors and cell signaling pathways in Sertoli TM4 cells. We proposed that molecular mechanism of reproductive damage in Sertoli cells induced by NPs may be mediated by cell receptors and/or cell signal transduction pathways, and that the effects were dependent on the side chain of NP isomers. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 469-476, 2017.
authors.affiliation: State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, 330047, China.
authors.forename: Xiaozhen
authors.initials: X
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, 330047, China.
authors.forename: Shaoping
authors.initials: S
authors.lastname: Nie
authors.affiliation: State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, 330047, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, 330047, China.
authors.forename: Xiaoyin
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, 330047, China.
authors.forename: Danfei
authors.initials: D
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, 330047, China.
authors.forename: Mingyong
authors.initials: M
authors.lastname: Xie
mesh_terms: D000818:Animals; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects; D052244:Endocrine Disruptors / Q000737:chemistry / Q000633:toxicity*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010636:Phenols / Q000737:chemistry / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D012708:Sertoli Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013237:Stereoisomerism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D052244:Endocrine Disruptors; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D010636:Phenols; D012333:RNA, Messenger; D011980:Receptors, Progesterone; C025256:nonylphenol; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Akt; TM4 cells; cell receptor; mitogen-activated protein kinases; nonylphenol isomer