Nano-selenium attenuates cadmium-induced ER-phagy through inhibition of TFEB nuclear translocation and FAM134B downregulation.

Cadmium (Cd) is a well-documented environmental pollutant associated with male reproductive disorders, necessitating the urgent development of effective therapeutic agents. Nano-selenium (Nano-Se) represents an advanced selenium supplement with robust antioxidant properties, which can mitigate various forms of heavy metal toxicity. However, the role of Nano-Se in alleviating Cd-induced testis damage remains unclear. Family with sequence similarity 134 member B (FAM134B) is the first identified Endoplasmic reticulophagy (ER-phagy) receptor, and the ER-phagy it mediates plays a crucial role in the reproductive system. In this study, Hy-line White roosters were randomly divided into four groups and subjected to a 90-day observation period. Serum samples and testicular tissue samples from roosters were collected for subsequent detection. Hematoxylin-eosin (H&E) staining, periodic acid-Schiff (PAS) staining, ELISA kit detection, Western blotting (WB), immunofluorescence (IF), cellular thermal shift assay (CETSA) and molecular docking techniques were employed to explore the effects of Cd on the reproductive system and the alleviating effect of Nano-Se. In vivo assays revealed that Nano-Se efficiently mitigated testicular atrophy and histological damage triggered by Cd exposure. Nano-Se reversed the Cd-mediated inhibition of steroidogenesis-related proteins, and elevated the expression of Leydig cell markers including 3β-HSD and INSL3, thereby ameliorating Cd-evoked Leydig cell dysfunction. Consistent with in vivo outcomes, in vitro tests using primary rooster Leydig cells demonstrated that Nano-Se notably restrained Cd-activated ER-phagy and excessive lysosomal acidification. Mechanistically, such protective effects were achieved by blocking TFEB nuclear translocation and preventing the downregulation of FAM134B. This present study provides a foundation for preclinical research for its usefulness as a potential therapeutic for reproductive toxicity induced by environmental heavy metal pollutants.