Effects of PFNA exposure on expression of junction-associated molecules and secretory function in rat Sertoli cells

Abstract

Perfluorononanoic acid (PFNA, C9), a synthetic perfluorinated chemical containing nine carbons, has been identified in humans and wildlife worldwide. Sertoli cell plays a key role in spermatogenesis; however, the toxic effects of PFNA on Sertoli cells have not been studied. The aim of this study was to investigate the effects of PFNA exposure on cell junction molecules and factors specifically secreted by Sertoli cells. Primary Sertoli cells from 20- to 21-day-old rats were exposed to increasing PFNA concentrations (0, 1, 10, 25, 50, or 75 μM) for 24 h. No significant changes in the expression of cytoskeleton-associated molecules were noted, although the mRNA levels of vimentin were upregulated dramatically in cells exposed to 50 and 75 μM PFNA. Meanwhile, the mRNA levels of Sertoli cell-specific secretions, such as Mullerian inhibiting substance (MIS), androgen binding protein (ABP), inhibin B, transferrin, and follicle-stimulating hormone receptor (FSH-R) changed significantly in experimental groups. Wilms’ tumor gene (WT1), a transcription factor, was upregulated significantly in cells exposed to 1–75 μM PFNA. In additional studies, male rats were exposed to 0, 1, 3, or 5 mg/kg-d PFNA for 14 days. Vacuoles in the cytoplasm of Sertoli cells were observed in the ultrastructure of testis. Furthermore, the changes in the concentrations of MIS and inhibin B in serum and the protein levels of WT1 and transferrin in testis were similar to the mRNA expression levels of those observed after in vitro treatment. In conclusion, these findings demonstrated that PFNA treatment led to the damage of specific secretory functions of Sertoli cells and that these effects might be an underlying cause of the male-specific reproductive toxicity of PFNA.