The main metabolite of fipronil, fipronil sulfone triggers morphological and functional damage to SerW3 cells and dysfunction in blood-testis barrier.

Fipronil sulfone (FS) is one of the main metabolites of the wide-spectrum insecticide fipronil, and it is used against non-agricultural pests. Exposure to fipronil is recognized for its detrimental effects on non-target organisms, including birds, bees, and mammals. Due to FS accumulation in testicular tissue, SerW3 Sertoli cell toxicity, morphology, and specifically the structure and functions of the blood-testis barrier (BTB) have been thoroughly investigated. In this study, SerW3 cells were exposed to 10, 20, and 40 µM FS, and the cell viability assay was conducted. The cell morphology and ultrastructure of the SerW3 cells were examined. The expressions of cytoskeletal F-actin protein and the cell junctional proteins including claudin-11, occludin, zonula occludens (ZO-1), N-cadherin, connexin-43, β-catenin were visualized by immunofluorescence microscopy. Additionally, the Western blot analyses and gene expression studies were carried out for the cell junctional proteins, and the cellular barrier function was evaluated through transepithelial electrical resistance measurement. FS exposure caused a dose-dependent decrease in cell viability in SerW3 cells. Morphological and subtle ultrastructural changes were observed in the cells by exposure. The relative protein and gene expression levels changed in response to FS exposure, and the physiological cellular barrier was affected adversely by FS according to the TEER measurement. This study provides an alternative perspective by focusing on the effects of fipronil or its metabolite FS on the BTB.