Downregulation of steroid hormone receptor expression and activation of cell signal transduction pathways induced by a chiral nonylphenol isomer in mouse sertoli TM4 cells

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• 作者：Xiaozhen Liu ; Shaoping Nie ; Qiang Yu ; Xiaoyin Wang ; Danfei Huang and Mingyong Xie
• 刊名：Environmental Toxicology
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：32
• 期：2
• 页码：469-476
• 全文大小：317K
• ISSN：1522-7278

文摘

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-NP₆₅ for 24 h. Furthermore, 4-NP₆₅ treatment 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-NP₆₅ challenged cells. Additionally, JNK1/2-MAPK pathway was activated due to 4-NP₆₅ exposure, but not ERK1/2 and p38-MAPK pathways. Meanwhile, 4-NP₆₅ increased 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-NP₆₅ exposure 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.