Abstract: Objective To explore the role of perfluorooctanoic acid(PFOA)in the tight junction function between Sertoli cells and its mechanism.Methods Primary Sertoli cells were isolated from 10 days old male ICR mice.Cytotoxicity assay,transepithelial electrical resistance(TER)analysis,flow cytometry,and immunoblotting analysis were used to explore the effects of PFOA on the Sertoli cells.Results There were no significant toxic effects observed after PFOA treatment at the dose range from 0 to 100 μmol/L for 12 to 24 hours(P>0.05 for all).In addition,50 μmol/L of PFOA did not change the apoptosis rate of Sertoli cells(9.7%±3.2%).However,TER values were significantly decreased(37.35±5.2 Ωcm² for PFOA group,49.85±6.4 Ωcm² for PFOA+PD90859 group;P<0.05).Meanwhile,claudin-11,zonula occludens-1,and occludin significantly decreased,while phosphorylated extracellular signal-regulated kinase(p-ERK)increased after the treatment of 50 μmol/L PFOA(P<0.05),which could be inhibited by PD90859.Conclusion PFOA disrupts tight junctions between Sertoli cells via activation of extracellular regulated protein kinase(ERK)/mitogen-activated protein kinase(MAPK)signal pathway.