Environmental arsenic (As) exposure impairs spermatogenesis and testicular function, but the underlying mechanism remains unclear. In this study, 6-week-old male mice and rat primary Sertoli cells were utilized to explore the mechanism of arsenic-induced spermatogenic impairment. Serum testosterone levels were measured, testicular histology and ultrastructure were assessed, and the expression of tight junction (TJ) proteins, actin-related proteins, cytokines, and key components of the MAPK pathway were further investigated. Our results indicated that arsenic exposure reduced sperm quality, altered histological structure of the testis, and impaired TJs and actin cytoskeleton in the spermatogenic epithelia. Further analysis demonstrated that arsenic suppressed the expression of TJ proteins (CLAUDIN-11, ZO-1) in both testis tissues and primary Sertoli cells. The mRNA level and localization of the actin-related protein (ARP3) were also altered following arsenic exposure. Additionally, arsenic treatment markedly elevated testicular levels of the cytokines IFN-γ and TGF-β3. The gene expression and phosphorylation level of p38 Mapk were significantly increased in arsenic-exposed mice. These findings demonstrate that interference with Sertoli cell junctions is an important factor in arsenic-induced spermatogenic dysfunction. TJ barrier permeability and F-actin realignment, which might be mediated by TGF-β3/p38 MAPK pathway, collectively contribute to the disruption of cell junction structure.
Li et al. (2026) studied this question.