Effects of 4-nonylphenol isomers on cell receptors and mitogen-activated protein kinase pathway in mouse Sertoli TM4 cells

• NP41 and NP42 influence expression levels of cell receptors in TM4 cells.
• NP41 and NP42 affect expression of BTB-associated elements and inhibin B secretion.
• NP41 and NP42 affected MAPK pathway with various degrees in TM4 cells.
• Effects of NPs on Sertoli cells may be mediated by cell receptor or MAPK pathway.
• Effects of NPs on Sertoli cells were related to the structure of NP isomer.

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 μM (P < 0.05), and increased mRNA levels of estrogen receptor (ER)-α and progesterone receptor in 1–40 μM (P < 0.05). NP42 treatment only evoked significant decrease in mRNA expression levels of ER-α in 20–40 μM (P < 0.05). Similarly, NP41 (1–40 μM) drastically increased the protein expression of ER-α, which was significantly decreased in 20–40 μM 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 (40 μM) and NP42 (10–40 μM) 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 μM) and NP42 (0.1–1 μM), and high concentrations of NP41 (40 μM) and NP42 (10–40 μM) 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.