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

Environ Toxicol. 2017 Feb;32(2):469-476. doi: 10.1002/tox.22251. Epub 2016 Apr 18.

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-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. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 469-476, 2017.

Keywords: Akt; TM4 cells; cell receptor; mitogen-activated protein kinases; nonylphenol isomer.

MeSH terms

  • Animals
  • Cell Line
  • Down-Regulation / drug effects
  • Endocrine Disruptors / chemistry
  • Endocrine Disruptors / toxicity*
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor alpha / metabolism
  • Estrogen Receptor beta / genetics
  • Estrogen Receptor beta / metabolism
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Male
  • Mice
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Phenols / chemistry
  • Phenols / toxicity*
  • RNA, Messenger / metabolism
  • Receptors, Progesterone / genetics
  • Receptors, Progesterone / metabolism
  • Sertoli Cells / cytology
  • Sertoli Cells / drug effects
  • Sertoli Cells / metabolism
  • Signal Transduction / drug effects*
  • Stereoisomerism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Endocrine Disruptors
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Phenols
  • RNA, Messenger
  • Receptors, Progesterone
  • nonylphenol
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases