Comparative Analysis of PFOS and PFOA Toxicity on Sertoli Cells

Abstract

Perfluoroalkyl chemicals induce male reproductive toxicity. Current evidence showed the effects of the chemical exposure on the deterioration of testicular functions, and reduction in epididymal sperm counts. Previous studies showed that PFOA and PFOS displayed a high correlation with each other in seminal plasma levels, but induced different effects on semen variables. In this study, we focused on the comparative toxicity analysis of PFOA and PFOS, using a rat primary Sertoli cell model. Our transcriptomic data showed that PFOA and PFOS treatments (40 μM) perturbed global gene expression. While PFOS induced higher toxicity in affecting cytoskeleton signaling, Sertoli cell−cell junction, and inflammation, underlined by Ingenuity pathway analysis. Immunocytochemical staining revealed that PFOS treatment (40 and 80 μM) induced truncated actin filament and disorganized bundled configuration in the cell cytoplasm. Moreover, disorganized distribution of N-cadherin (N-cad) and β-catenin (β-cat), and defragmentation of ZO-1 at the Sertoli cell− cell interface was evident. At 80 μM of PFOS, cytoplasmic distribution of N-cad, β-cat, and ZO-1 were observed. We then examined whether resveratrol, a polyphenol antioxidant, was able to protect the cells from PFOS toxicity. The pretreatment of Sertoli cells with 10 μM resveratrol prevented the formation of truncated actin filament and dis-localization of β-cat. Western blot analysis showed that Res pretreatment increased the levels of basal ES proteins (N-cad and β-cat), tight junction proteins (ZO-1 and occludin), and gap junction protein, versus control.

A Flavonoid-Rich Extract from Bergamot Juice, Alone or in Association with Curcumin and Resveratrol, Shows Protective Effects in a Murine Model of Cadmium-Induced Testicular Injury

“…In this regard, in rodents challenged with Cd, Cur improved seminiferous tubules morphology [ 26 , 27 ] and significantly decreased the number of apoptotic germinal cells [ 28 , 29 ]. Additionally, resveratrol (Re), a polyphenol present in many plants and especially in red wine, showed antioxidant properties [ 30 ] as well a positive regulation of apoptosis and other zonula occludens protein expression, such as occludin [ 31 , 32 ]. In the testis, Re protected from oxidative stress [ 33 ], partially reversed the dysregulation of the apoptotic pathways [ 20 ], and improved sperm parameters and histopathological damage [ 34 ].…”

Icariin attenuates perfluorooctane sulfonate-induced testicular toxicity by alleviating Sertoli cell injury and downregulating the p38MAPK/MMP9 pathway

“…42 It is reported that PFOS directly acts on testicular Sertoli cells in mice and disrupts BTB integrity by disturbing the expression and localization of TJ-related proteins (ZO-1, Occludin, Claudin-11) and GJ-related protein (CX43), leading to spermatogenic dysfunction and infertility. 27,43 However, there is less information on whether icariin protects testicular Sertoli cells from damage caused by PFOS. Our findings demonstrated that icariin alleviated the disruption of BTB integrity and the junctional damage of Sertoli cells by downregulating the expression levels of TJ-and GJ-related proteins in vivo and in vitro, thereby improving the PFOS-induced disorders of testicular function.…”

Insights into the Competitive Mechanisms of Per- and Polyfluoroalkyl Substances Partition in Liver and Blood

“…Due to the widespread production and persistence, PFASs have become ubiquitous environmental contaminants . Perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) are the most frequently detected PFASs in environmental compartments and are believed to exert potential toxic effects on human health. , Since 3 M Company stopped producing PFOS in 2000, the government agencies in many countries issued a series of regulations to restrict the production and application of PFOA and PFOS, , for example, PFOS was listed as an Annex B substance under the Stockholm Convention . To meet the industrial demands, many novel PFASs were widely identified and applied as their alternatives and consequently released into the environment .…”