Liu Xiaozhen, Nie Shaoping, Chen Yangjie, Huang Danfei, Xie Mingyong
State Key Laboratory of Food Science and Technology, Nanchang University, 235 Nanjing East Road, Nanchang 330047, China.
State Key Laboratory of Food Science and Technology, Nanchang University, 235 Nanjing East Road, Nanchang 330047, China.
Toxicology. 2014 Dec 4;326:1-8. doi: 10.1016/j.tox.2014.09.009. Epub 2014 Sep 19.
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.
在本研究中，进行了实验以探究壬基酚（NP）异构体（4-[1,2,4-三甲基己基]苯酚（NP41）、4-[1,2,5-三甲基己基]苯酚（NP42））对睾丸支持细胞TM4的影响。NP41在20 - 40μM时降低雄激素受体和Toll样受体（TLR）-4的mRNA表达水平（P<0.05），并在1 - 40μM时增加雌激素受体（ER）-α和孕激素受体的mRNA水平（P<0.05）。NP42处理仅在20 - 40μM时引起ER-α的mRNA表达水平显著降低（P<0.05）。同样，NP41（1 - 40μM）显著增加ER-α的蛋白表达，而在20 - 40μM的NP42组中该表达显著降低（P<0.01）。NP41和NP42对ER-β的表达均无影响。在高浓度NP41（40μM）和NP42（10 - 40μM）刺激的细胞中促卵泡激素受体的蛋白水平显著升高。此外，NP41和NP42对TM4细胞中连接相关分子的表达和抑制素B分泌有不同影响。另外，NP41和NP42诱导JNK1/2通路的激活。然而，在暴露于低浓度NP41（0.1 - 20μM）和NP42（0.1 - 1μM）的TM4细胞中ERK1/2和p38通路被抑制，而高浓度NP41（40μM）和NP42（10 - 40μM）导致p-ERK1/2和p-p38恢复到对照水平。我们提出，NP诱导的睾丸支持细胞生殖损伤的分子机制可能由细胞受体和/或细胞信号通路介导，且这些影响可能与NP异构体的结构有关。
