Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
Reprod Toxicol. 2010 Nov;30(3):429-37. doi: 10.1016/j.reprotox.2010.05.010. Epub 2010 May 16.
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 24h. 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 5mg/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.
全氟壬酸（PFNA，C9）是一种含有九个碳原子的合成全氟化学物质，已在全球范围内的人类和野生动物中被发现。Sertoli 细胞在精子发生中起着关键作用；然而，PFNA 对 Sertoli 细胞的毒性作用尚未得到研究。本研究旨在探讨 PFNA 暴露对细胞连接分子和 Sertoli 细胞特异性分泌因子的影响。从 20-21 天大的大鼠中分离出初级 Sertoli 细胞，并用不同浓度的 PFNA（0、1、10、25、50 或 75 μM）处理 24 小时。虽然暴露于 50 和 75 μM PFNA 的细胞中 vimentin 的 mRNA 水平显著上调，但未观察到细胞骨架相关分子表达的显著变化。同时，Müllerian 抑制物质（MIS）、雄激素结合蛋白（ABP）、抑制素 B、转铁蛋白和卵泡刺激素受体（FSH-R）等 Sertoli 细胞特异性分泌物的 mRNA 水平在实验组中发生了显著变化。Wilms 肿瘤基因（WT1），一种转录因子，在暴露于 1-75 μM PFNA 的细胞中显著上调。在进一步的研究中，雄性大鼠暴露于 0、1、3 或 5mg/kg-d PFNA 14 天。在睾丸的超微结构中观察到 Sertoli 细胞细胞质中的空泡。此外，血清中 MIS 和抑制素 B 浓度以及睾丸中 WT1 和转铁蛋白的蛋白水平的变化与体外处理后观察到的 mRNA 表达水平相似。总之，这些发现表明 PFNA 处理导致 Sertoli 细胞特定分泌功能受损，这可能是 PFNA 雄性特异性生殖毒性的潜在原因。
