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Technical nonylphenol contains at least 20 para-substituted isomers.It has beenshown that NP isomers vary in their estrogenic potency,and it washeavilydependent upon the structure of the side chain.4-[1,2,4-trimethylhexyl]-phenol(NP41)and4-[1,2,5-trimethylhexyl]-phenol(NP42)aretwo of the main isomers of technical nonylphenol mixtures.In the present study,experiments were performed to investigate the effects of nonylphenol(NP)isomers(NP41,NP42)on SertoliTM4 cells.NP41 decreased mRNA expression levels of androgen receptor and toll-like receptor(TLR)-4 in 20-40 μM,and increased mRNA levels ofestrogen receptor(ER)-αand progesterone receptor in 1-40 μM.NP42 treatment only evoked significant decrease in mRNA expression levels of ER-αin 20-40 μM.Similarly,NP41(1-40 μM)drastically increased the protein expression of ER-α,which was significantly decreased in 20-40 μM NP42 groups.Both NP41and NP42 showed no effect on the expression of ER-β.Proteinlevels of follicle stimulating hormone receptor were increased significantly in high concentrations ofNP41(40 μM)and NP42(10-40 μM)challenged cells.Furthermore,NP41 and NP42 showed various effects on the expression ofjunction-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.